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A.; Lobell, A. title: Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date: 2008-06-28 journal: Scand J Immunol DOI: 10.1111/j.0300-9475.2004.01423j.x sha: doc_id: 23389 cord_uid: ilrp8vb7 file: cache/cord-023950-nv0pbbu2.json key: cord-023950-nv0pbbu2 authors: Schnyder, Bruno; Schnyder-Candrian, Silvia title: Dual Role of Th17 Cytokines, IL-17A,F, and IL-22 in Allergic Asthma date: 2012-07-19 journal: IL-17, IL-22 and Their Producing Cells: Role in Inflammation and Autoimmunity DOI: 10.1007/978-3-0348-0522-3_10 sha: doc_id: 23950 cord_uid: nv0pbbu2 file: cache/cord-016523-pznw2ciu.json key: cord-016523-pznw2ciu authors: Fouqué, Amélie; Legembre, Patrick title: The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date: 2014-08-29 journal: Cancer Immunology DOI: 10.1007/978-3-662-44006-3_9 sha: doc_id: 16523 cord_uid: pznw2ciu file: cache/cord-016960-xhzvp35g.json key: cord-016960-xhzvp35g authors: Berencsi, György; Szomor, Katalin N. title: Fetal and Neonatal Illnesses Caused or Influenced by Maternal Transplacental IgG and/or Therapeutic Antibodies Applied During Pregnancy date: 2012-03-08 journal: Maternal Fetal Transmission of Human Viruses and their Influence on Tumorigenesis DOI: 10.1007/978-94-007-4216-1_9 sha: doc_id: 16960 cord_uid: xhzvp35g file: cache/cord-017470-sjk7a34u.json key: cord-017470-sjk7a34u authors: Arlati, Sergio title: Pathophysiology of Acute Illness and Injury date: 2018-06-14 journal: Operative Techniques and Recent Advances in Acute Care and Emergency Surgery DOI: 10.1007/978-3-319-95114-0_2 sha: doc_id: 17470 cord_uid: sjk7a34u file: cache/cord-013803-d1sbfibq.json key: cord-013803-d1sbfibq authors: Abu El-Asrar, Ahmed M.; Berghmans, Nele; Al-Obeidan, Saleh A.; Gikandi, Priscilla W.; Opdenakker, Ghislain; Van Damme, Jo; Struyf, Sofie title: Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis date: 2019-12-05 journal: Eye (Lond) DOI: 10.1038/s41433-019-0693-7 sha: doc_id: 13803 cord_uid: d1sbfibq file: cache/cord-023433-d1b7qvhs.json key: cord-023433-d1b7qvhs authors: Siassi, M.; Hohenberger, W.; Croner, R. title: Expression of Human Collectins in Colorectal Carcinoma date: 2008-06-28 journal: Scand J Immunol DOI: 10.1111/j.0300-9475.2004.01423bo.x sha: doc_id: 23433 cord_uid: d1b7qvhs file: cache/cord-017309-pt27efu1.json key: cord-017309-pt27efu1 authors: Gupta, G. 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T. title: Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation date: 2008-06-28 journal: Scand J Immunol DOI: 10.1111/j.0300-9475.2004.01423bm.x sha: doc_id: 23410 cord_uid: eblcf902 file: cache/cord-023407-s85g7g0x.json key: cord-023407-s85g7g0x authors: Huang, Y.‐M.; Liu, X.; Steffensen, K.; Sanna, A.; Arru, G.; Sominanda, A.; Sotgiu, S.; Rosati, G.; Gustafsson, J.‐Å.; Link, H. title: Anti‐Inflammatory Liver X Receptors and Related Molecules in Multiple Sclerosis Patients from Sardinia and Sweden date: 2008-06-28 journal: Scand J Immunol DOI: 10.1111/j.0300-9475.2004.01423d.x sha: doc_id: 23407 cord_uid: s85g7g0x file: cache/cord-262511-96xp1v0r.json key: cord-262511-96xp1v0r authors: Khabar, Khalid S. 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Wang, Yanfei; Vilekar, Prachi; Yang, Seung-Pil; Gupta, Mayuri; Oh, Myong In; Meek, Autumn; Doyle, Lisa; Villar, Laura; Brennecke, Anja; Liyanage, Imindu; Reed, Mark; Barden, Christopher; Weaver, Donald F. title: Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide date: 2020-07-07 journal: PeerJ DOI: 10.7717/peerj.9533 sha: doc_id: 336432 cord_uid: tu00gffr file: cache/cord-301102-jbjysyqm.json key: cord-301102-jbjysyqm authors: Priestnall, Simon L.; Mitchell, Judy A.; Brooks, Harriet W.; Brownlie, Joe; Erles, Kerstin title: Quantification of mRNA encoding cytokines and chemokines and assessment of ciliary function in canine tracheal epithelium during infection with canine respiratory coronavirus (CRCoV) date: 2009-01-15 journal: Vet Immunol Immunopathol DOI: 10.1016/j.vetimm.2008.09.017 sha: doc_id: 301102 cord_uid: jbjysyqm file: cache/cord-316904-g7dli0a8.json key: cord-316904-g7dli0a8 authors: Chang, Hernan R.; Dulloo, Abdul G.; Bistrian, Bruce R. title: Role of cytokines in AIDS wasting date: 1998-12-31 journal: Nutrition DOI: 10.1016/s0899-9007(98)00108-7 sha: doc_id: 316904 cord_uid: g7dli0a8 file: cache/cord-309171-kgc7lgjp.json key: cord-309171-kgc7lgjp authors: Dolinger, Michael T.; Person, Hannibal; Smith, Rachel; Jarchin, Lauren; Pittman, Nanci; Dubinsky, Marla C.; Lai, Joanne title: Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab date: 2020-05-21 journal: J Pediatr Gastroenterol Nutr DOI: 10.1097/mpg.0000000000002809 sha: doc_id: 309171 cord_uid: kgc7lgjp file: cache/cord-324949-sqy03dks.json key: cord-324949-sqy03dks authors: Poe, Francis L.; Corn, Joshua title: N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2 date: 2020-05-30 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109862 sha: doc_id: 324949 cord_uid: sqy03dks file: cache/cord-322250-7kjakuyw.json key: cord-322250-7kjakuyw authors: He, Jia; Yuan, Renyikun; Cui, Xiaolan; Cui, Yushun; Han, Shan; Wang, Qin-Qin; Chen, Yangling; Huang, Liting; Yang, Shilin; Xu, Qiongming; Zhao, Yonghui; Gao, Hongwei title: Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice date: 2020-07-02 journal: Chin Med DOI: 10.1186/s13020-020-00350-w sha: doc_id: 322250 cord_uid: 7kjakuyw file: cache/cord-308433-vrkdtrfz.json key: cord-308433-vrkdtrfz authors: Roberts, Ceri A.; Durham, Lucy E.; Fleskens, Veerle; Evans, Hayley G.; Taams, Leonie S. title: TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells date: 2017-02-15 journal: Front Immunol DOI: 10.3389/fimmu.2017.00157 sha: doc_id: 308433 cord_uid: vrkdtrfz file: cache/cord-339272-trd6rkxw.json key: cord-339272-trd6rkxw authors: Chen, Na; Wu, Qianchao; Chi, Gefu; Soromou, Lanan Wassy; Hou, Jinli; Deng, Yanhong; Feng, Haihua title: Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice date: 2013-04-24 journal: Int Immunopharmacol DOI: 10.1016/j.intimp.2013.04.014 sha: doc_id: 339272 cord_uid: trd6rkxw file: cache/cord-317628-1inxq7t5.json key: cord-317628-1inxq7t5 authors: Cuccarese, Michael F.; Earnshaw, Berton A.; Heiser, Katie; Fogelson, Ben; Davis, Chadwick T.; McLean, Peter F.; Gordon, Hannah B.; Skelly, Kathleen-Rose; Weathersby, Fiona L.; Rodic, Vlad; Quigley, Ian K.; Pastuzyn, Elissa D.; Mendivil, Brandon M.; Lazar, Nathan H.; Brooks, Carl A.; Carpenter, Joseph; Probst, Brandon L.; Jacobson, Pamela; Glazier, Seth W.; Ford, Jes; Jensen, James D.; Campbell, Nicholas D.; Statnick, Michael A.; Low, Adeline S.; Thomas, Kirk R.; Carpenter, Anne E.; Hegde, Sharath S.; Alfa, Ronald W.; Victors, Mason L.; Haque, Imran S.; Chong, Yolanda T.; Gibson, Christopher C. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 journal: bioRxiv DOI: 10.1101/2020.08.02.233064 sha: doc_id: 317628 cord_uid: 1inxq7t5 file: cache/cord-319121-et957lfl.json key: cord-319121-et957lfl authors: Mifflin, Lauren; Ofengeim, Dimitry; Yuan, Junying title: Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target date: 2020-07-15 journal: Nat Rev Drug Discov DOI: 10.1038/s41573-020-0071-y sha: doc_id: 319121 cord_uid: et957lfl file: cache/cord-295745-iw3ftw3h.json key: cord-295745-iw3ftw3h authors: Gershoni, Jonathan M title: Molecular decoys: antidotes, therapeutics and immunomodulators date: 2008-11-18 journal: Curr Opin Biotechnol DOI: 10.1016/j.copbio.2008.10.001 sha: doc_id: 295745 cord_uid: iw3ftw3h file: cache/cord-330549-ppuqvafd.json key: cord-330549-ppuqvafd authors: Christophi, George P.; Panos, Michael; Hudson, Chad A.; Christophi, Rebecca L.; Gruber, Ross C.; Mersich, Akos T.; Blystone, Scott D.; Jubelt, Burk; Massa, Paul T. title: Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype date: 2009-04-27 journal: Lab Invest DOI: 10.1038/labinvest.2009.32 sha: doc_id: 330549 cord_uid: ppuqvafd file: cache/cord-006230-xta38e7j.json key: cord-006230-xta38e7j authors: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 journal: Naunyn Schmiedebergs Arch Pharmacol DOI: 10.1007/s00210-012-0736-0 sha: doc_id: 6230 cord_uid: xta38e7j file: cache/cord-332071-bqvn3ceq.json key: cord-332071-bqvn3ceq authors: Lee, Jeong Seok; Park, Seongwan; Jeong, Hye Won; Ahn, Jin Young; Choi, Seong Jin; Lee, Hoyoung; Choi, Baekgyu; Nam, Su Kyung; Sa, Moa; Kwon, Ji-Soo; Jeong, Su Jin; Lee, Heung Kyu; Park, Sung Ho; Park, Su-Hyung; Choi, Jun Yong; Kim, Sung-Han; Jung, Inkyung; 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Li, Qiang; Ryu, Min-Ok; Nam, Aryung; An, Ju-Hyun; Jung, Yun Chan; Ahn, Jin-Ok; Youn, Hwa-Young title: Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice date: 2019-08-31 journal: Research in Veterinary Science DOI: 10.1016/j.rvsc.2019.06.012 sha: doc_id: 323553 cord_uid: bukm9m9q file: cache/cord-346669-7n75m669.json key: cord-346669-7n75m669 authors: Wang, Shixin; Wei, Maoti; Han, Yi; Zhang, Keju; He, Li; Yang, Zhen; Su, Bing; Zhang, Zhilun; Hu, Yilan; Hui, Wuli title: Roles of TNF-α gene polymorphisms in the occurrence and progress of SARS-Cov infection: A case-control study date: 2008-02-29 journal: BMC Infect Dis DOI: 10.1186/1471-2334-8-27 sha: doc_id: 346669 cord_uid: 7n75m669 file: cache/cord-348391-xytmq2f2.json key: cord-348391-xytmq2f2 authors: Wyganowska-Swiatkowska, Marzena; Nohawica, Michal; Grocholewicz, Katarzyna; Nowak, Gerard title: Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review date: 2020-06-30 journal: Int J Mol Sci DOI: 10.3390/ijms21134639 sha: doc_id: 348391 cord_uid: xytmq2f2 file: cache/cord-354492-6r6qs4pp.json key: cord-354492-6r6qs4pp authors: Messina, Giovanni; Polito, Rita; Monda, Vincenzo; Cipolloni, Luigi; Di Nunno, Nunzio; Di Mizio, Giulio; Murabito, Paolo; Carotenuto, Marco; Messina, Antonietta; Pisanelli, Daniela; Valenzano, Anna; Cibelli, Giuseppe; Scarinci, Alessia; Monda, Marcellino; Sessa, Francesco title: Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work date: 2020-04-28 journal: Int J Mol Sci DOI: 10.3390/ijms21093104 sha: doc_id: 354492 cord_uid: 6r6qs4pp file: cache/cord-353887-f4yd7guj.json key: cord-353887-f4yd7guj authors: Tang, Yujun; Liu, Jiajia; Zhang, Dingyi; Xu, Zhenghao; Ji, Jinjun; Wen, Chengping title: Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies date: 2020-07-10 journal: Front Immunol DOI: 10.3389/fimmu.2020.01708 sha: doc_id: 353887 cord_uid: f4yd7guj file: cache/cord-336510-qzm9wgde.json key: cord-336510-qzm9wgde authors: Ellermann-Eriksen, Svend title: Macrophages and cytokines in the early defence against herpes simplex virus date: 2005-08-03 journal: Virol J DOI: 10.1186/1743-422x-2-59 sha: doc_id: 336510 cord_uid: qzm9wgde file: cache/cord-335185-3qi29i6n.json key: cord-335185-3qi29i6n authors: Hendry, Bruce M.; Stafford, Nina; Arnold, Ahran D.; Sangwaiya, Arvind; Manglam, Vijay; Rosen, Stuart D.; Arnold, Jayantha title: Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID‐19 patients date: 2020-07-26 journal: Pharmacol Res Perspect DOI: 10.1002/prp2.631 sha: doc_id: 335185 cord_uid: 3qi29i6n file: cache/cord-348855-lnltoj1n.json key: cord-348855-lnltoj1n authors: Iannaccone, Giulia; Scacciavillani, Roberto; Del Buono, Marco Giuseppe; Camilli, Massimiliano; Ronco, Claudio; Lavie, Carl J.; Abbate, Antonio; Crea, Filippo; Massetti, Massimo; Aspromonte, Nadia title: Weathering the Cytokine Storm in COVID-19: Therapeutic Implications date: 2020-06-29 journal: Cardiorenal Med DOI: 10.1159/000509483 sha: doc_id: 348855 cord_uid: lnltoj1n file: cache/cord-351387-i0zamkpd.json key: cord-351387-i0zamkpd authors: Witte, Katrin; Koch, Egon; Volk, Hans-Dieter; Wolk, Kerstin; Sabat, Robert title: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date: 2015-09-25 journal: PLoS One DOI: 10.1371/journal.pone.0138075 sha: doc_id: 351387 cord_uid: i0zamkpd file: cache/cord-340741-bhxm4zua.json key: cord-340741-bhxm4zua authors: Nayak, Tapas Kumar; Mamidi, Prabhudutta; Sahoo, Subhransu Sekhar; Kumar, P. Sanjai; Mahish, Chandan; Chatterjee, Sanchari; Subudhi, Bharat Bhusan; Chattopadhyay, Soma; Chattopadhyay, Subhasis title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date: 2019-04-12 journal: Front Immunol DOI: 10.3389/fimmu.2019.00786 sha: doc_id: 340741 cord_uid: bhxm4zua file: cache/cord-344204-qq2vqzc2.json key: cord-344204-qq2vqzc2 authors: Hariharan, Apurva; Hakeem, Abdul Rahman; Radhakrishnan, Subathra; Reddy, Mettu Srinivas; Rela, Mohamed title: The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients date: 2020-11-07 journal: Inflammopharmacology DOI: 10.1007/s10787-020-00773-9 sha: doc_id: 344204 cord_uid: qq2vqzc2 file: cache/cord-347298-7kqrl3rv.json key: cord-347298-7kqrl3rv authors: Hedger, M.P. title: Immunology of the Testis and Male Reproductive Tract date: 2010-07-12 journal: Comprehensive Toxicology DOI: 10.1016/b978-0-08-046884-6.01112-x sha: doc_id: 347298 cord_uid: 7kqrl3rv file: cache/cord-341667-ayl71jpc.json key: cord-341667-ayl71jpc authors: Van Reeth, Kristien; Nauwynck, Hans; Pensaert, Maurice title: Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans? date: 1998-04-17 journal: J Infect Dis DOI: 10.1086/517398 sha: doc_id: 341667 cord_uid: ayl71jpc file: cache/cord-337414-8ndkjs1i.json key: cord-337414-8ndkjs1i authors: Burgmaier, Gruscha; Schönrock, Lisa M.; Kuhlmann, Tanja; Richter‐Landsberg, Christiane; Brück, Wolfgang title: Association of Increased Bcl‐2 Expression with Rescue from Tumor Necrosis Factor‐α‐Induced Cell Death in the Oligodendrocyte Cell Line OLN‐93 date: 2008-07-29 journal: J Neurochem DOI: 10.1046/j.1471-4159.2000.0752270.x sha: doc_id: 337414 cord_uid: 8ndkjs1i file: cache/cord-354765-abayh871.json key: cord-354765-abayh871 authors: Graham, R. S.; Zachs, D. P.; Cotero, V.; DAgostino, C.; Ntiloudi, D.; Kaiser, C. R.; Graf, J.; Wallace, K.; Coleman, T. R.; Ashe, J.; Pellerito, J.; Tracey, K. J.; Binstadt, B.; Chavan, S. S.; Zanos, S.; Puleo, C.; Peterson, E.; Lim, H. H. title: Calming the Cytokine Storm - Splenic Ultrasound for Treating Inflammatory Disorders and Potentially COVID-19 date: 2020-07-17 journal: nan DOI: 10.1101/2020.07.14.20153528 sha: doc_id: 354765 cord_uid: abayh871 file: cache/cord-355847-1ru15s5a.json key: cord-355847-1ru15s5a authors: Convertino, Irma; Tuccori, Marco; Ferraro, Sara; Valdiserra, Giulia; Cappello, Emiliano; Focosi, Daniele; Blandizzi, Corrado title: Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in COVID-19 patients date: 2020-06-11 journal: Crit Care DOI: 10.1186/s13054-020-03020-3 sha: doc_id: 355847 cord_uid: 1ru15s5a file: cache/cord-022888-dnsdg04n.json key: cord-022888-dnsdg04n authors: nan title: Poster Sessions date: 2009-08-19 journal: Eur J Immunol DOI: 10.1002/eji.200990224 sha: doc_id: 22888 cord_uid: dnsdg04n file: cache/cord-015021-pol2qm74.json key: cord-015021-pol2qm74 authors: nan title: Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date: 1994 journal: Intensive Care Med DOI: 10.1007/bf02258437 sha: doc_id: 15021 cord_uid: pol2qm74 file: cache/cord-005814-ak5pq312.json key: cord-005814-ak5pq312 authors: nan title: 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date: 1995 journal: Intensive Care Med DOI: 10.1007/bf02426401 sha: doc_id: 5814 cord_uid: ak5pq312 file: cache/cord-022940-atbjwpo5.json key: cord-022940-atbjwpo5 authors: nan title: Poster Sessions date: 2016-09-07 journal: FEBS J DOI: 10.1111/febs.13808 sha: doc_id: 22940 cord_uid: atbjwpo5 file: cache/cord-015394-uj7fe5y6.json key: cord-015394-uj7fe5y6 authors: nan title: Scientific Abstracts date: 2008-12-23 journal: Reprod Sci DOI: 10.1177/19337191080150020102 sha: doc_id: 15394 cord_uid: uj7fe5y6 Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-tnf-cord === file2bib.sh === id: cord-004919-d7tilk8v author: Baker, Rahaf title: Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab date: 2018-12-07 pages: extension: .txt txt: ./txt/cord-004919-d7tilk8v.txt cache: ./cache/cord-004919-d7tilk8v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004919-d7tilk8v.txt' === file2bib.sh === id: cord-005983-2ascbu62 author: Eigler, A. title: Suppression der Synthese des Tumornekrosefaktors date: 2001 pages: extension: .txt txt: ./txt/cord-005983-2ascbu62.txt cache: ./cache/cord-005983-2ascbu62.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005983-2ascbu62.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45555 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45633 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45635 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44718 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45507 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-005664-n4xv247l author: Plötz, Frans B. title: Mechanical ventilation alters the immune response in children without lung pathology date: 2002-01-15 pages: extension: .txt txt: ./txt/cord-005664-n4xv247l.txt cache: ./cache/cord-005664-n4xv247l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-005664-n4xv247l.txt' === file2bib.sh === id: cord-103625-p55ew8w7 author: Ramana, Chilakamarti V. title: Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-103625-p55ew8w7.txt cache: ./cache/cord-103625-p55ew8w7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103625-p55ew8w7.txt' === file2bib.sh === id: cord-003013-h8txbd3p author: Kim, Sena title: Differential Regulation of Toll-Like Receptor-Mediated Cytokine Production by Unfolded Protein Response date: 2018-04-24 pages: extension: .txt txt: ./txt/cord-003013-h8txbd3p.txt cache: ./cache/cord-003013-h8txbd3p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003013-h8txbd3p.txt' === file2bib.sh === id: cord-016168-3hyb9stq author: nan title: Pathogenesis of Fever date: 2009 pages: extension: .txt txt: ./txt/cord-016168-3hyb9stq.txt cache: ./cache/cord-016168-3hyb9stq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016168-3hyb9stq.txt' === file2bib.sh === id: cord-023950-nv0pbbu2 author: Schnyder, Bruno title: Dual Role of Th17 Cytokines, IL-17A,F, and IL-22 in Allergic Asthma date: 2012-07-19 pages: extension: .txt txt: ./txt/cord-023950-nv0pbbu2.txt cache: ./cache/cord-023950-nv0pbbu2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-023950-nv0pbbu2.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45581 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 45805 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-007613-g4s0v8ra author: Rimstad, Espen title: Cloning, expression and characterization of biologically active feline tumour necrosis factor-α date: 2000-03-10 pages: extension: .txt txt: ./txt/cord-007613-g4s0v8ra.txt cache: ./cache/cord-007613-g4s0v8ra.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007613-g4s0v8ra.txt' === file2bib.sh === id: cord-013183-t25gecuw author: Beloumi, Dhekra title: Inflammatory Correlated Response in Two Lines of Rabbit Selected Divergently for Litter Size Environmental Variability date: 2020-09-01 pages: extension: .txt txt: ./txt/cord-013183-t25gecuw.txt cache: ./cache/cord-013183-t25gecuw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013183-t25gecuw.txt' === file2bib.sh === id: cord-021266-afs9eb40 author: El Gendy, Fady M. title: The role of Tumor necrosis factor alpha −308 G>A promoter polymorphism in pediatric community acquired pneumonia date: 2020-02-10 pages: extension: .txt txt: ./txt/cord-021266-afs9eb40.txt cache: ./cache/cord-021266-afs9eb40.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-021266-afs9eb40.txt' === file2bib.sh === id: cord-017639-wtc8bml5 author: El-Radhi, A. Sahib title: Pathogenesis of Fever date: 2019-01-02 pages: extension: .txt txt: ./txt/cord-017639-wtc8bml5.txt cache: ./cache/cord-017639-wtc8bml5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017639-wtc8bml5.txt' === file2bib.sh === id: cord-006770-m5wqk6rh author: Rook, Graham A. W. title: Evaluation of TNF as antiviral, antibacterial and antiparasitic agent date: 1991 pages: extension: .txt txt: ./txt/cord-006770-m5wqk6rh.txt cache: ./cache/cord-006770-m5wqk6rh.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-006770-m5wqk6rh.txt' === file2bib.sh === id: cord-007858-1ijxilpb author: Xu, G.L. title: Attenuation of acute lung injury in mice by oxymatrine is associated with inhibition of phosphorylated p38 mitogen-activated protein kinase date: 2005-04-08 pages: extension: .txt txt: ./txt/cord-007858-1ijxilpb.txt cache: ./cache/cord-007858-1ijxilpb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-007858-1ijxilpb.txt' === file2bib.sh === id: cord-013366-sbdtpsz6 author: Ramírez-Pérez, Sergio title: Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-013366-sbdtpsz6.txt cache: ./cache/cord-013366-sbdtpsz6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013366-sbdtpsz6.txt' === file2bib.sh === id: cord-000324-to4g9he9 author: Spentzas, Thomas title: Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus date: 2011-01-25 pages: extension: .txt txt: ./txt/cord-000324-to4g9he9.txt cache: ./cache/cord-000324-to4g9he9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000324-to4g9he9.txt' === file2bib.sh === id: cord-272237-gnno6elo author: Wang, Ziran title: A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids date: 2020-07-31 pages: extension: .txt txt: ./txt/cord-272237-gnno6elo.txt cache: ./cache/cord-272237-gnno6elo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-272237-gnno6elo.txt' === file2bib.sh === id: cord-276564-o21ncldx author: Miller, R. title: COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-276564-o21ncldx.txt cache: ./cache/cord-276564-o21ncldx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-276564-o21ncldx.txt' === file2bib.sh === id: cord-009326-dvhkk405 author: Lee, Jae Min title: Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation date: 2020-03-14 pages: extension: .txt txt: ./txt/cord-009326-dvhkk405.txt cache: ./cache/cord-009326-dvhkk405.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-009326-dvhkk405.txt' === file2bib.sh === id: cord-013803-d1sbfibq author: Abu El-Asrar, Ahmed M. title: Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis date: 2019-12-05 pages: extension: .txt txt: ./txt/cord-013803-d1sbfibq.txt cache: ./cache/cord-013803-d1sbfibq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013803-d1sbfibq.txt' === file2bib.sh === id: cord-007621-rapinodd author: Vidovic, Maria title: Induction and regulation of class II major histocompatibility complex mRNA expression in astrocytes by interferon-γ and tumor necrosis factor-α date: 2002-11-13 pages: extension: .txt txt: ./txt/cord-007621-rapinodd.txt cache: ./cache/cord-007621-rapinodd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007621-rapinodd.txt' === file2bib.sh === id: cord-002326-3qb1ym4w author: Yang, Runkuan title: Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries date: 2016-12-03 pages: extension: .txt txt: ./txt/cord-002326-3qb1ym4w.txt cache: ./cache/cord-002326-3qb1ym4w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002326-3qb1ym4w.txt' === file2bib.sh === id: cord-001293-dfaxj3bv author: Cavaillon, Jean-Marc title: Is boosting the immune system in sepsis appropriate? date: 2014-03-24 pages: extension: .txt txt: ./txt/cord-001293-dfaxj3bv.txt cache: ./cache/cord-001293-dfaxj3bv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001293-dfaxj3bv.txt' === file2bib.sh === id: cord-002209-xs6qigg4 author: Kıray, Hülya title: The multifaceted role of astrocytes in regulating myelination date: 2016-09-17 pages: extension: .txt txt: ./txt/cord-002209-xs6qigg4.txt cache: ./cache/cord-002209-xs6qigg4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002209-xs6qigg4.txt' === file2bib.sh === id: cord-267270-r17z4d8x author: Kipar, A. title: Age-related dynamics of constitutive cytokine transcription levels of feline monocytes date: 2005-01-18 pages: extension: .txt txt: ./txt/cord-267270-r17z4d8x.txt cache: ./cache/cord-267270-r17z4d8x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267270-r17z4d8x.txt' === file2bib.sh === id: cord-262511-96xp1v0r author: Khabar, Khalid S. A. title: Rapid transit in the immune cells: the role of mRNA turnover regulation date: 2007-03-30 pages: extension: .txt txt: ./txt/cord-262511-96xp1v0r.txt cache: ./cache/cord-262511-96xp1v0r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-262511-96xp1v0r.txt' === file2bib.sh === id: cord-002079-jne14jqf author: MacParland, Sonya A. title: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date: 2016-05-27 pages: extension: .txt txt: ./txt/cord-002079-jne14jqf.txt cache: ./cache/cord-002079-jne14jqf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-002079-jne14jqf.txt' === file2bib.sh === id: cord-017520-r786yd6i author: Huber-Lang, Markus title: Inflammatory Changes and Coagulopathy in Multiply Injured Patients date: 2015-05-14 pages: extension: .txt txt: ./txt/cord-017520-r786yd6i.txt cache: ./cache/cord-017520-r786yd6i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017520-r786yd6i.txt' === file2bib.sh === id: cord-272695-wmzq4lkh author: Ahmed, Ahmed A. title: TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-272695-wmzq4lkh.txt cache: ./cache/cord-272695-wmzq4lkh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272695-wmzq4lkh.txt' === file2bib.sh === id: cord-295683-eoxxal8v author: Gong, R. title: Hepatocyte growth factor suppresses acute renal inflammation by inhibition of endothelial E-selectin date: 2006-04-01 pages: extension: .txt txt: ./txt/cord-295683-eoxxal8v.txt cache: ./cache/cord-295683-eoxxal8v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-295683-eoxxal8v.txt' === file2bib.sh === id: cord-270414-gh9agf4x author: Fischer, Y. title: Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis date: 2011-10-12 pages: extension: .txt txt: ./txt/cord-270414-gh9agf4x.txt cache: ./cache/cord-270414-gh9agf4x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-270414-gh9agf4x.txt' === file2bib.sh === id: cord-278339-6ddsj014 author: Gianfrancesco, Milena title: Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-278339-6ddsj014.txt cache: ./cache/cord-278339-6ddsj014.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-278339-6ddsj014.txt' === file2bib.sh === id: cord-259586-kep2dgaw author: Van Reeth, Kristien title: In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding date: 2002-09-10 pages: extension: .txt txt: ./txt/cord-259586-kep2dgaw.txt cache: ./cache/cord-259586-kep2dgaw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-259586-kep2dgaw.txt' === file2bib.sh === id: cord-271114-hv3gwvdi author: Allam, Gamal title: Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms date: 2015-04-22 pages: extension: .txt txt: ./txt/cord-271114-hv3gwvdi.txt cache: ./cache/cord-271114-hv3gwvdi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271114-hv3gwvdi.txt' === file2bib.sh === id: cord-269986-jdcw59r2 author: Regan, Andrew D. title: Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells date: 2009-02-05 pages: extension: .txt txt: ./txt/cord-269986-jdcw59r2.txt cache: ./cache/cord-269986-jdcw59r2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269986-jdcw59r2.txt' === file2bib.sh === id: cord-001039-qocuprwb author: Hayasaka, Daisuke title: TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection date: 2013-08-05 pages: extension: .txt txt: ./txt/cord-001039-qocuprwb.txt cache: ./cache/cord-001039-qocuprwb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001039-qocuprwb.txt' === file2bib.sh === id: cord-006518-al94gxjw author: Calder, Philip C. title: n−3 Fatty acids, inflammation, and immunity— Relevance to postsurgical and critically III patients date: 2004 pages: extension: .txt txt: ./txt/cord-006518-al94gxjw.txt cache: ./cache/cord-006518-al94gxjw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-006518-al94gxjw.txt' === file2bib.sh === id: cord-003686-1pfk4qve author: Kaneko, Naoe title: The role of interleukin-1 in general pathology date: 2019-06-06 pages: extension: .txt txt: ./txt/cord-003686-1pfk4qve.txt cache: ./cache/cord-003686-1pfk4qve.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003686-1pfk4qve.txt' === file2bib.sh === id: cord-017640-i8h48ny6 author: Fouqué, Amélie title: The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date: 2020-01-03 pages: extension: .txt txt: ./txt/cord-017640-i8h48ny6.txt cache: ./cache/cord-017640-i8h48ny6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-017640-i8h48ny6.txt' === file2bib.sh === id: cord-020757-q4ivezyq author: Saikumar, Pothana title: Apoptosis and Cell Death: Relevance to Lung date: 2010-05-21 pages: extension: .txt txt: ./txt/cord-020757-q4ivezyq.txt cache: ./cache/cord-020757-q4ivezyq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-020757-q4ivezyq.txt' === file2bib.sh === id: cord-005872-w1x1i0im author: Volk, T. title: Endothelium function in sepsis date: 2000 pages: extension: .txt txt: ./txt/cord-005872-w1x1i0im.txt cache: ./cache/cord-005872-w1x1i0im.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-005872-w1x1i0im.txt' === file2bib.sh === id: cord-006610-me8rhkcg author: Nör, Jacques E. title: Role of endothelial cell survival and death signals in angiogenesis date: 1999 pages: extension: .txt txt: ./txt/cord-006610-me8rhkcg.txt cache: ./cache/cord-006610-me8rhkcg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-006610-me8rhkcg.txt' === file2bib.sh === id: cord-256837-100ir651 author: Smith, Steven B. title: Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date: 2012-03-14 pages: extension: .txt txt: ./txt/cord-256837-100ir651.txt cache: ./cache/cord-256837-100ir651.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-256837-100ir651.txt' === file2bib.sh === id: cord-016523-pznw2ciu author: Fouqué, Amélie title: The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date: 2014-08-29 pages: extension: .txt txt: ./txt/cord-016523-pznw2ciu.txt cache: ./cache/cord-016523-pznw2ciu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-016523-pznw2ciu.txt' === file2bib.sh === id: cord-280599-7ixpqd5n author: OPENSHAW, P J M title: What does the peripheral blood tell you in SARS? date: 2004-04-01 pages: extension: .txt txt: ./txt/cord-280599-7ixpqd5n.txt cache: ./cache/cord-280599-7ixpqd5n.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-280599-7ixpqd5n.txt' === file2bib.sh === id: cord-018764-02l423mk author: Clark, Ian A. title: The molecular basis of paediatric malarial disease date: 2007 pages: extension: .txt txt: ./txt/cord-018764-02l423mk.txt cache: ./cache/cord-018764-02l423mk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-018764-02l423mk.txt' === file2bib.sh === id: cord-275413-e2rhioty author: Rowland, Raymond R.R. title: The interaction between PRRSV and the late gestation pig fetus date: 2010-09-09 pages: extension: .txt txt: ./txt/cord-275413-e2rhioty.txt cache: ./cache/cord-275413-e2rhioty.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275413-e2rhioty.txt' === file2bib.sh === id: cord-295523-5pv7kw6i author: Picchianti Diamanti, Andrea title: Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-295523-5pv7kw6i.txt cache: ./cache/cord-295523-5pv7kw6i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295523-5pv7kw6i.txt' === file2bib.sh === id: cord-256838-8rzibpbl author: Eng, Yi Shin title: Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples date: 2019-09-27 pages: extension: .txt txt: ./txt/cord-256838-8rzibpbl.txt cache: ./cache/cord-256838-8rzibpbl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-256838-8rzibpbl.txt' === file2bib.sh === id: cord-023935-o2ffxgnn author: Lorts, Angela title: Sepsis date: 2011-12-16 pages: extension: .txt txt: ./txt/cord-023935-o2ffxgnn.txt cache: ./cache/cord-023935-o2ffxgnn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023935-o2ffxgnn.txt' === file2bib.sh === id: cord-252725-e3pazjdi author: Khalil, Ayman title: The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-252725-e3pazjdi.txt cache: ./cache/cord-252725-e3pazjdi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252725-e3pazjdi.txt' === file2bib.sh === id: cord-275730-650sjwyy author: Gogoi, Himanshu title: The Age of Cyclic Dinucleotide Vaccine Adjuvants date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-275730-650sjwyy.txt cache: ./cache/cord-275730-650sjwyy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275730-650sjwyy.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51961 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52062 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-283246-dj7teo89 author: Otsuka, Ryo title: Macrophage activation syndrome and COVID-19 date: 2020-08-06 pages: extension: .txt txt: ./txt/cord-283246-dj7teo89.txt cache: ./cache/cord-283246-dj7teo89.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-283246-dj7teo89.txt' === file2bib.sh === id: cord-002119-kl431ev6 author: Garcia, Elisa title: Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury date: 2016-06-23 pages: extension: .txt txt: ./txt/cord-002119-kl431ev6.txt cache: ./cache/cord-002119-kl431ev6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002119-kl431ev6.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52316 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-297128-s5c9h4lm author: Hong, Joung-Woo title: Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models date: 2012-11-28 pages: extension: .txt txt: ./txt/cord-297128-s5c9h4lm.txt cache: ./cache/cord-297128-s5c9h4lm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297128-s5c9h4lm.txt' === file2bib.sh === id: cord-023928-9a1w174h author: Thomas, Neal J. title: Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date: 2011-12-16 pages: extension: .txt txt: ./txt/cord-023928-9a1w174h.txt cache: ./cache/cord-023928-9a1w174h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023928-9a1w174h.txt' === file2bib.sh === id: cord-309171-kgc7lgjp author: Dolinger, Michael T. title: Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-309171-kgc7lgjp.txt cache: ./cache/cord-309171-kgc7lgjp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309171-kgc7lgjp.txt' === file2bib.sh === id: cord-302258-derq9b27 author: Zhang, Hui title: Effects of ubiquitin-proteasome inhibitor on the expression levels of TNF-α and TGF-β1 in mice with viral myocarditis date: 2019-08-14 pages: extension: .txt txt: ./txt/cord-302258-derq9b27.txt cache: ./cache/cord-302258-derq9b27.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302258-derq9b27.txt' === file2bib.sh === id: cord-282242-5tkhjiwl author: Gómez-Laguna, J. title: Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus date: 2009-08-19 pages: extension: .txt txt: ./txt/cord-282242-5tkhjiwl.txt cache: ./cache/cord-282242-5tkhjiwl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-282242-5tkhjiwl.txt' === file2bib.sh === id: cord-313227-6zwkfzab author: Scala, Stefania title: Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-313227-6zwkfzab.txt cache: ./cache/cord-313227-6zwkfzab.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-313227-6zwkfzab.txt' === file2bib.sh === id: cord-301946-erzh30mt author: Kwak-Kim, Joanne title: COVID-19 and immunomodulation treatment for women with reproductive failures date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-301946-erzh30mt.txt cache: ./cache/cord-301946-erzh30mt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-301946-erzh30mt.txt' === file2bib.sh === id: cord-279498-ez3yq7xi author: Suzumura, Akio title: Immune Response in the Brain: Glial Response and Cytokine Production date: 2008-12-31 pages: extension: .txt txt: ./txt/cord-279498-ez3yq7xi.txt cache: ./cache/cord-279498-ez3yq7xi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-279498-ez3yq7xi.txt' === file2bib.sh === id: cord-023421-1d1gf7az author: Sønder, S. U. S. title: Monitoring Patients Treated with Type 1 Interferons: Antiviral versus MxA Induction Assays date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023421-1d1gf7az.txt cache: ./cache/cord-023421-1d1gf7az.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023421-1d1gf7az.txt' === file2bib.sh === id: cord-259367-2e998to9 author: Jacques, Alexandre title: Macrophage interleukin-6 and tumour necrosis factor-α are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a date: 2009-09-01 pages: extension: .txt txt: ./txt/cord-259367-2e998to9.txt cache: ./cache/cord-259367-2e998to9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-259367-2e998to9.txt' === file2bib.sh === id: cord-291076-p350i54m author: Wang, Renxi title: The role of C5a in acute lung injury induced by highly pathogenic viral infections date: 2015-05-06 pages: extension: .txt txt: ./txt/cord-291076-p350i54m.txt cache: ./cache/cord-291076-p350i54m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-291076-p350i54m.txt' === file2bib.sh === id: cord-300991-ipy24zxp author: Khan, Amira Sayed title: Obesity and COVID-19: Oro-Naso-Sensory Perception date: 2020-07-08 pages: extension: .txt txt: ./txt/cord-300991-ipy24zxp.txt cache: ./cache/cord-300991-ipy24zxp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-300991-ipy24zxp.txt' === file2bib.sh === id: cord-023441-q83y12sk author: Draborg, H. title: Recominant Expression and Immunological Characterization of House Dust Mite Allergen Der P 1 date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023441-q83y12sk.txt cache: ./cache/cord-023441-q83y12sk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023441-q83y12sk.txt' === file2bib.sh === id: cord-023393-8nye3nc8 author: Krarup, A. title: Mannan‐Binding Lectin, L‐Ficolin and H‐Ficolin Selectively Binds to Different Bacteria date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023393-8nye3nc8.txt cache: ./cache/cord-023393-8nye3nc8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023393-8nye3nc8.txt' === file2bib.sh === id: cord-308008-s2t11l3h author: Limonta, Daniel title: Apoptotic mediators in patients with severe and non‐severe dengue from Brazil date: 2013-10-29 pages: extension: .txt txt: ./txt/cord-308008-s2t11l3h.txt cache: ./cache/cord-308008-s2t11l3h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308008-s2t11l3h.txt' === file2bib.sh === id: cord-015910-d9gxew91 author: Grimble, Robert F. title: The Interaction Between Nutrition and Inflammatory Stress Throughout the Life Cycle date: 2005 pages: extension: .txt txt: ./txt/cord-015910-d9gxew91.txt cache: ./cache/cord-015910-d9gxew91.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-015910-d9gxew91.txt' === file2bib.sh === id: cord-306983-6w2fvtfy author: Wang, Siye title: Influenza Virus—Cytokine-Protease Cycle in the Pathogenesis of Vascular Hyperpermeability in Severe Influenza date: 2010-10-01 pages: extension: .txt txt: ./txt/cord-306983-6w2fvtfy.txt cache: ./cache/cord-306983-6w2fvtfy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306983-6w2fvtfy.txt' === file2bib.sh === id: cord-324949-sqy03dks author: Poe, Francis L. title: N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2 date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-324949-sqy03dks.txt cache: ./cache/cord-324949-sqy03dks.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324949-sqy03dks.txt' === file2bib.sh === id: cord-271812-ldwb05xn author: Prasad, Ananda S. title: Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease(1)(2)(3) date: 2013-03-01 pages: extension: .txt txt: ./txt/cord-271812-ldwb05xn.txt cache: ./cache/cord-271812-ldwb05xn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271812-ldwb05xn.txt' === file2bib.sh === id: cord-023394-ptfjxpo6 author: Isa, A. title: Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023394-ptfjxpo6.txt cache: ./cache/cord-023394-ptfjxpo6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023394-ptfjxpo6.txt' === file2bib.sh === id: cord-023373-6wh1kb3p author: Melchjorsen, J. title: Differential Requirements for Toll‐Like Receptor Signalling for Induction of Chemokine Expression by Herpes Simplex Virus and Sendai Virus date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023373-6wh1kb3p.txt cache: ./cache/cord-023373-6wh1kb3p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023373-6wh1kb3p.txt' === file2bib.sh === id: cord-297857-ybqj8z1r author: Petagna, L. title: Pathophysiology of Crohn’s disease inflammation and recurrence date: 2020-11-07 pages: extension: .txt txt: ./txt/cord-297857-ybqj8z1r.txt cache: ./cache/cord-297857-ybqj8z1r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297857-ybqj8z1r.txt' === file2bib.sh === id: cord-322250-7kjakuyw author: He, Jia title: Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-322250-7kjakuyw.txt cache: ./cache/cord-322250-7kjakuyw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-322250-7kjakuyw.txt' === file2bib.sh === id: cord-023374-87ob1exq author: Sukhija, S. title: Levels, Complement Activity and Polymorphisms of Mannan‐Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023374-87ob1exq.txt cache: ./cache/cord-023374-87ob1exq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023374-87ob1exq.txt' === file2bib.sh === id: cord-023375-x4p187u7 author: Alitalo, A. title: Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023375-x4p187u7.txt cache: ./cache/cord-023375-x4p187u7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023375-x4p187u7.txt' === file2bib.sh === id: cord-023372-ft8cp9op author: Rahman, Q. K. title: The Immunomodulatory Effect of Heat Shock Protein 70: Immunization with a DNA Construct Based on the Malarial Antigen Fused with a Fragment of HSP 70 Primes for a Th‐1 Type of Response date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023372-ft8cp9op.txt cache: ./cache/cord-023372-ft8cp9op.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023372-ft8cp9op.txt' === file2bib.sh === id: cord-336432-tu00gffr author: Wang, Zhiyu title: Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-336432-tu00gffr.txt cache: ./cache/cord-336432-tu00gffr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336432-tu00gffr.txt' === file2bib.sh === id: cord-301102-jbjysyqm author: Priestnall, Simon L. title: Quantification of mRNA encoding cytokines and chemokines and assessment of ciliary function in canine tracheal epithelium during infection with canine respiratory coronavirus (CRCoV) date: 2009-01-15 pages: extension: .txt txt: ./txt/cord-301102-jbjysyqm.txt cache: ./cache/cord-301102-jbjysyqm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-301102-jbjysyqm.txt' === file2bib.sh === id: cord-333650-4towah1t author: Malmo, Jostein title: Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date: 2016-05-12 pages: extension: .txt txt: ./txt/cord-333650-4towah1t.txt cache: ./cache/cord-333650-4towah1t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333650-4towah1t.txt' === file2bib.sh === id: cord-022631-s4n24xij author: Jonsson, M. V. title: Germinal Centres in Primary Sjögren's Syndrome Indicate a Certain Clinical Immunological Phenotype date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-022631-s4n24xij.txt cache: ./cache/cord-022631-s4n24xij.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-022631-s4n24xij.txt' === file2bib.sh === id: cord-023443-pvz7dll9 author: nan title: Abstracts for the Scandinavian Society for Immunology 35th Annual Meeting and 20th Summer School date: 2004-06-02 pages: extension: .txt txt: ./txt/cord-023443-pvz7dll9.txt cache: ./cache/cord-023443-pvz7dll9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023443-pvz7dll9.txt' === file2bib.sh === id: cord-023433-d1b7qvhs author: Siassi, M. title: Expression of Human Collectins in Colorectal Carcinoma date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023433-d1b7qvhs.txt cache: ./cache/cord-023433-d1b7qvhs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023433-d1b7qvhs.txt' === file2bib.sh === id: cord-023392-axd0901z author: Hansen, T. K. title: Association between Mannose‐Binding Lectin and Vascular Complications in Type 1 Diabetes date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023392-axd0901z.txt cache: ./cache/cord-023392-axd0901z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023392-axd0901z.txt' === file2bib.sh === id: cord-310942-191m0e65 author: Boga, Jose Antonio title: Beneficial actions of melatonin in the management of viral infections: a new use for this “molecular handyman”? date: 2012-04-18 pages: extension: .txt txt: ./txt/cord-310942-191m0e65.txt cache: ./cache/cord-310942-191m0e65.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310942-191m0e65.txt' === file2bib.sh === id: cord-341667-ayl71jpc author: Van Reeth, Kristien title: Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans? date: 1998-04-17 pages: extension: .txt txt: ./txt/cord-341667-ayl71jpc.txt cache: ./cache/cord-341667-ayl71jpc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341667-ayl71jpc.txt' === file2bib.sh === id: cord-339272-trd6rkxw author: Chen, Na title: Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice date: 2013-04-24 pages: extension: .txt txt: ./txt/cord-339272-trd6rkxw.txt cache: ./cache/cord-339272-trd6rkxw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339272-trd6rkxw.txt' === file2bib.sh === id: cord-016960-xhzvp35g author: Berencsi, György title: Fetal and Neonatal Illnesses Caused or Influenced by Maternal Transplacental IgG and/or Therapeutic Antibodies Applied During Pregnancy date: 2012-03-08 pages: extension: .txt txt: ./txt/cord-016960-xhzvp35g.txt cache: ./cache/cord-016960-xhzvp35g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-016960-xhzvp35g.txt' === file2bib.sh === id: cord-346669-7n75m669 author: Wang, Shixin title: Roles of TNF-α gene polymorphisms in the occurrence and progress of SARS-Cov infection: A case-control study date: 2008-02-29 pages: extension: .txt txt: ./txt/cord-346669-7n75m669.txt cache: ./cache/cord-346669-7n75m669.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346669-7n75m669.txt' === file2bib.sh === id: cord-023431-zjyrhlxn author: Sigmundsdóttir, H. title: Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023431-zjyrhlxn.txt cache: ./cache/cord-023431-zjyrhlxn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023431-zjyrhlxn.txt' === file2bib.sh === id: cord-306577-gq6fss5l author: Hsueh, Wei title: Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts date: 2002-11-11 pages: extension: .txt txt: ./txt/cord-306577-gq6fss5l.txt cache: ./cache/cord-306577-gq6fss5l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306577-gq6fss5l.txt' === file2bib.sh === id: cord-308433-vrkdtrfz author: Roberts, Ceri A. title: TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells date: 2017-02-15 pages: extension: .txt txt: ./txt/cord-308433-vrkdtrfz.txt cache: ./cache/cord-308433-vrkdtrfz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-308433-vrkdtrfz.txt' === file2bib.sh === id: cord-023402-8qfmo6rq author: Reinholdt, J. title: Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype‐Specific Human Monoclonal IgA1 Antibodies date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023402-8qfmo6rq.txt cache: ./cache/cord-023402-8qfmo6rq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023402-8qfmo6rq.txt' === file2bib.sh === id: cord-351310-6p42b144 author: Bohr, Adam title: Treatment of acute lung inflammation by pulmonary delivery of anti-TNF-α siRNA with PAMAM dendrimers in a murine model date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-351310-6p42b144.txt cache: ./cache/cord-351310-6p42b144.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351310-6p42b144.txt' === file2bib.sh === id: cord-295745-iw3ftw3h author: Gershoni, Jonathan M title: Molecular decoys: antidotes, therapeutics and immunomodulators date: 2008-11-18 pages: extension: .txt txt: ./txt/cord-295745-iw3ftw3h.txt cache: ./cache/cord-295745-iw3ftw3h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-295745-iw3ftw3h.txt' === file2bib.sh === id: cord-023389-ilrp8vb7 author: Wefer, J. title: Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023389-ilrp8vb7.txt cache: ./cache/cord-023389-ilrp8vb7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023389-ilrp8vb7.txt' === file2bib.sh === id: cord-023410-eblcf902 author: Kollgaard, T. M. title: Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023410-eblcf902.txt cache: ./cache/cord-023410-eblcf902.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023410-eblcf902.txt' === file2bib.sh === id: cord-023391-bq5w3jk9 author: Utermöhlen, O. title: Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023391-bq5w3jk9.txt cache: ./cache/cord-023391-bq5w3jk9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023391-bq5w3jk9.txt' === file2bib.sh === id: cord-309619-glb2y82u author: Domingo, Pere title: The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19) date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-309619-glb2y82u.txt cache: ./cache/cord-309619-glb2y82u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309619-glb2y82u.txt' === file2bib.sh === id: cord-323553-bukm9m9q author: Song, Woo-Jin title: Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice date: 2019-08-31 pages: extension: .txt txt: ./txt/cord-323553-bukm9m9q.txt cache: ./cache/cord-323553-bukm9m9q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323553-bukm9m9q.txt' === file2bib.sh === id: cord-351387-i0zamkpd author: Witte, Katrin title: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date: 2015-09-25 pages: extension: .txt txt: ./txt/cord-351387-i0zamkpd.txt cache: ./cache/cord-351387-i0zamkpd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351387-i0zamkpd.txt' === file2bib.sh === id: cord-023414-xxw5kptr author: Chistensen, H. R. title: Characterization of a Large Panel of Lactic Acid Bacteria Derived from the Human Gut for their Capacity to Polarize Dendritic Cell date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023414-xxw5kptr.txt cache: ./cache/cord-023414-xxw5kptr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023414-xxw5kptr.txt' === file2bib.sh === id: cord-316904-g7dli0a8 author: Chang, Hernan R. title: Role of cytokines in AIDS wasting date: 1998-12-31 pages: extension: .txt txt: ./txt/cord-316904-g7dli0a8.txt cache: ./cache/cord-316904-g7dli0a8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316904-g7dli0a8.txt' === file2bib.sh === id: cord-023415-hhvmsn5b author: Karlsson, H. title: Pattern of Cytokine Responses to Gram‐Positive and Gram‐Negative Commensal Bacteria is Profoundly Changed when Monocytes Differentiate into Dendritic Cells date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023415-hhvmsn5b.txt cache: ./cache/cord-023415-hhvmsn5b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023415-hhvmsn5b.txt' === file2bib.sh === id: cord-023430-5zuewjv2 author: Nilkaeo, A. title: Interleukin‐18 Inhibition of Oral Carcinoma Cell Proliferation date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023430-5zuewjv2.txt cache: ./cache/cord-023430-5zuewjv2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023430-5zuewjv2.txt' === file2bib.sh === id: cord-355847-1ru15s5a author: Convertino, Irma title: Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in COVID-19 patients date: 2020-06-11 pages: extension: .txt txt: ./txt/cord-355847-1ru15s5a.txt cache: ./cache/cord-355847-1ru15s5a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-355847-1ru15s5a.txt' === file2bib.sh === id: cord-023445-c4tqioz1 author: Lauridsen, C. title: Supplementation of Vitamin C to Weaner Diets Increases IgM Concentration and Improves the Biological Activity of Vitamin E in Alveolar Macrophages date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023445-c4tqioz1.txt cache: ./cache/cord-023445-c4tqioz1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023445-c4tqioz1.txt' === file2bib.sh === id: cord-332071-bqvn3ceq author: Lee, Jeong Seok title: Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-332071-bqvn3ceq.txt cache: ./cache/cord-332071-bqvn3ceq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-332071-bqvn3ceq.txt' === file2bib.sh === id: cord-023387-tyeh14wz author: Hvas, C. L. title: Probiotic Bacteria Induce Regulatory Cytokine Production via Dendritic Cells date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023387-tyeh14wz.txt cache: ./cache/cord-023387-tyeh14wz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023387-tyeh14wz.txt' === file2bib.sh === id: cord-023388-btbf6wkg author: Hoffmann, H. J. title: Decrease in Fine T‐cell Subset ratio MT2/MT1 During Steroid Reduction of Asthmatic Patients date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023388-btbf6wkg.txt cache: ./cache/cord-023388-btbf6wkg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023388-btbf6wkg.txt' === file2bib.sh === id: cord-023429-x52gbklw author: Ruseva, M. title: Mannan‐Binding Lectin Inhibits Humoural Responses date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023429-x52gbklw.txt cache: ./cache/cord-023429-x52gbklw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023429-x52gbklw.txt' === file2bib.sh === id: cord-023407-s85g7g0x author: Huang, Y.‐M. title: Anti‐Inflammatory Liver X Receptors and Related Molecules in Multiple Sclerosis Patients from Sardinia and Sweden date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023407-s85g7g0x.txt cache: ./cache/cord-023407-s85g7g0x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023407-s85g7g0x.txt' === file2bib.sh === id: cord-354492-6r6qs4pp author: Messina, Giovanni title: Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-354492-6r6qs4pp.txt cache: ./cache/cord-354492-6r6qs4pp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354492-6r6qs4pp.txt' === file2bib.sh === id: cord-023439-r04y1j22 author: Hedegaard, C. J. title: The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4(+) T‐cell Responses to MBP in Health and Multiple Sclerosis date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023439-r04y1j22.txt cache: ./cache/cord-023439-r04y1j22.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023439-r04y1j22.txt' === file2bib.sh === id: cord-330549-ppuqvafd author: Christophi, George P. title: Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype date: 2009-04-27 pages: extension: .txt txt: ./txt/cord-330549-ppuqvafd.txt cache: ./cache/cord-330549-ppuqvafd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-330549-ppuqvafd.txt' === file2bib.sh === id: cord-344204-qq2vqzc2 author: Hariharan, Apurva title: The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients date: 2020-11-07 pages: extension: .txt txt: ./txt/cord-344204-qq2vqzc2.txt cache: ./cache/cord-344204-qq2vqzc2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344204-qq2vqzc2.txt' === file2bib.sh === id: cord-023438-g0k0vvdc author: Krog, J. title: The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells, with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023438-g0k0vvdc.txt cache: ./cache/cord-023438-g0k0vvdc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023438-g0k0vvdc.txt' === file2bib.sh === id: cord-348391-xytmq2f2 author: Wyganowska-Swiatkowska, Marzena title: Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-348391-xytmq2f2.txt cache: ./cache/cord-348391-xytmq2f2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-348391-xytmq2f2.txt' === file2bib.sh === id: cord-317628-1inxq7t5 author: Cuccarese, Michael F. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-317628-1inxq7t5.txt cache: ./cache/cord-317628-1inxq7t5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-317628-1inxq7t5.txt' === file2bib.sh === id: cord-340741-bhxm4zua author: Nayak, Tapas Kumar title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date: 2019-04-12 pages: extension: .txt txt: ./txt/cord-340741-bhxm4zua.txt cache: ./cache/cord-340741-bhxm4zua.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340741-bhxm4zua.txt' === file2bib.sh === id: cord-353887-f4yd7guj author: Tang, Yujun title: Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-353887-f4yd7guj.txt cache: ./cache/cord-353887-f4yd7guj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-353887-f4yd7guj.txt' === file2bib.sh === id: cord-354765-abayh871 author: Graham, R. S. title: Calming the Cytokine Storm - Splenic Ultrasound for Treating Inflammatory Disorders and Potentially COVID-19 date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-354765-abayh871.txt cache: ./cache/cord-354765-abayh871.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-354765-abayh871.txt' === file2bib.sh === id: cord-319121-et957lfl author: Mifflin, Lauren title: Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-319121-et957lfl.txt cache: ./cache/cord-319121-et957lfl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319121-et957lfl.txt' === file2bib.sh === id: cord-307813-elom30nx author: Yip, Tsz-Fung title: Advancements in Host-Based Interventions for Influenza Treatment date: 2018-07-10 pages: extension: .txt txt: ./txt/cord-307813-elom30nx.txt cache: ./cache/cord-307813-elom30nx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307813-elom30nx.txt' === file2bib.sh === id: cord-017309-pt27efu1 author: Gupta, G. S. title: Selectins and Associated Adhesion Proteins in Inflammatory disorders date: 2012-03-20 pages: extension: .txt txt: ./txt/cord-017309-pt27efu1.txt cache: ./cache/cord-017309-pt27efu1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017309-pt27efu1.txt' === file2bib.sh === id: cord-336510-qzm9wgde author: Ellermann-Eriksen, Svend title: Macrophages and cytokines in the early defence against herpes simplex virus date: 2005-08-03 pages: extension: .txt txt: ./txt/cord-336510-qzm9wgde.txt cache: ./cache/cord-336510-qzm9wgde.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-336510-qzm9wgde.txt' === file2bib.sh === id: cord-347298-7kqrl3rv author: Hedger, M.P. title: Immunology of the Testis and Male Reproductive Tract date: 2010-07-12 pages: extension: .txt txt: ./txt/cord-347298-7kqrl3rv.txt cache: ./cache/cord-347298-7kqrl3rv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-347298-7kqrl3rv.txt' === file2bib.sh === id: cord-006828-i88on326 author: nan title: Abstracts DGRh-Kongress 2013 date: 2013-09-15 pages: extension: .txt txt: ./txt/cord-006828-i88on326.txt cache: ./cache/cord-006828-i88on326.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-006828-i88on326.txt' === file2bib.sh === id: cord-022353-q2k2krnm author: W. Quimby, Fred title: Clinical Chemistry of the Laboratory Mouse date: 2007-09-02 pages: extension: .txt txt: ./txt/cord-022353-q2k2krnm.txt cache: ./cache/cord-022353-q2k2krnm.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-022353-q2k2krnm.txt' === file2bib.sh === id: cord-006444-eq56zhtd author: nan title: Abstracts of oral presentations and posters date: 1993 pages: extension: .txt txt: ./txt/cord-006444-eq56zhtd.txt cache: ./cache/cord-006444-eq56zhtd.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006444-eq56zhtd.txt' === file2bib.sh === id: cord-034340-3ksfpaf7 author: nan title: Proceedings of the 26th European Paediatric Rheumatology Congress: part 2: Virtual. 23 - 26 September 2020 date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-034340-3ksfpaf7.txt cache: ./cache/cord-034340-3ksfpaf7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-034340-3ksfpaf7.txt' === file2bib.sh === id: cord-020643-0yzkqykg author: Müller-Werdan, U. title: Schock date: 2006 pages: extension: .txt txt: ./txt/cord-020643-0yzkqykg.txt cache: ./cache/cord-020643-0yzkqykg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-020643-0yzkqykg.txt' === file2bib.sh === id: cord-015147-h0o0yqv8 author: nan title: Oral Communications and Posters date: 2014-09-12 pages: extension: .txt txt: ./txt/cord-015147-h0o0yqv8.txt cache: ./cache/cord-015147-h0o0yqv8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-015147-h0o0yqv8.txt' === file2bib.sh === id: cord-004879-pgyzluwp author: nan title: Programmed cell death date: 1994 pages: extension: .txt txt: ./txt/cord-004879-pgyzluwp.txt cache: ./cache/cord-004879-pgyzluwp.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-004879-pgyzluwp.txt' === file2bib.sh === id: cord-022526-j9kg00qf author: Jones, Samuel L. title: Disorders of the Gastrointestinal System date: 2009-05-18 pages: extension: .txt txt: ./txt/cord-022526-j9kg00qf.txt cache: ./cache/cord-022526-j9kg00qf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 10 resourceName b'cord-022526-j9kg00qf.txt' === file2bib.sh === id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 pages: extension: .txt txt: ./txt/cord-006230-xta38e7j.txt cache: ./cache/cord-006230-xta38e7j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-006230-xta38e7j.txt' === file2bib.sh === id: cord-015021-pol2qm74 author: nan title: Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date: 1994 pages: extension: .txt txt: ./txt/cord-015021-pol2qm74.txt cache: ./cache/cord-015021-pol2qm74.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-015021-pol2qm74.txt' === file2bib.sh === id: cord-005814-ak5pq312 author: nan title: 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date: 1995 pages: extension: .txt txt: ./txt/cord-005814-ak5pq312.txt cache: ./cache/cord-005814-ak5pq312.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-005814-ak5pq312.txt' === file2bib.sh === id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 pages: extension: .txt txt: ./txt/cord-022888-dnsdg04n.txt cache: ./cache/cord-022888-dnsdg04n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 14 resourceName b'cord-022888-dnsdg04n.txt' === file2bib.sh === id: cord-022940-atbjwpo5 author: nan title: Poster Sessions date: 2016-09-07 pages: extension: .txt txt: ./txt/cord-022940-atbjwpo5.txt cache: ./cache/cord-022940-atbjwpo5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 38 resourceName b'cord-022940-atbjwpo5.txt' === file2bib.sh === id: cord-015394-uj7fe5y6 author: nan title: Scientific Abstracts date: 2008-12-23 pages: extension: .txt txt: ./txt/cord-015394-uj7fe5y6.txt cache: ./cache/cord-015394-uj7fe5y6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 18 resourceName b'cord-015394-uj7fe5y6.txt' Que is empty; done keyword-tnf-cord === reduce.pl bib === id = cord-001039-qocuprwb author = Hayasaka, Daisuke title = TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection date = 2013-08-05 pages = extension = .txt mime = text/plain words = 8562 sentences = 464 flesch = 51 summary = We next compared severe or mild cases of mice infected with JEV exhibiting doseindependent mortality and investigated the specific host responses such as TNF-α and IL-10 expression in the CNS. Corresponding to the viral loads, histopathological examination showed that a large number of neurons displayed JEV antigens and severe cuffing was observed in the brain cortex of JaTH160-infected mice at 9 day pi ( Figure 1F ). Following inoculation with JaOArS982 virus, there were no significant differences of infectious viral loads in the brain cortex between WT, IL-10 KO and TNF-α KO at 5, 9 and 11 days pi ( Figure 5B ). TNF-α KO mice exhibited significantly increased levels of IFN-γ and IL-5 in the brains compared with WT and/or IL-10 KO mice at 5 and 7 days pi following JaTH160 inoculation ( Figure 7C and D) . cache = ./cache/cord-001039-qocuprwb.txt txt = ./txt/cord-001039-qocuprwb.txt === reduce.pl bib === id = cord-002326-3qb1ym4w author = Yang, Runkuan title = Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries date = 2016-12-03 pages = extension = .txt mime = text/plain words = 7622 sentences = 310 flesch = 36 summary = EP (40 mg/kg) was intraperitoneally injected every 6 h for 48 h)] significantly ameliorates pancreatic injury and necrosis [4, 6] ; EP therapy also markedly reduces pancreatic expression of TNF-α, IL-6, HMGB1 and NF-kB DNA binding [4, 6] ; treatment with EP reduces the number of inflammatory cell infiltration and decreases the pancreatic level of lipid peroxidation, which is a parameter of ROS [4] . Hepatic I/R induces significantly increased hepatic expression of TNF-α, IL-6, HMGB1 and NF-kB activation, and hepatic I/R also induces markedly increased hepatic expression of Bcl-2, Bax, Beclin-1 and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, all of these changes are significantly reduced by EP treatment (1 h before the ischemia procedure, a single dose of EP was intraperitoneally injected to animals in the 20 mg/kg group, the 40 mg/kg group and the 80 mg/kg group, liver tissue samples were obtained 4 h, 6 h and 16 h after I/R), suggesting that EP ameliorates hepatic I/R injury via its antiinflammatory and its anti-apoptosis effect. cache = ./cache/cord-002326-3qb1ym4w.txt txt = ./txt/cord-002326-3qb1ym4w.txt === reduce.pl bib === id = cord-006610-me8rhkcg author = Nör, Jacques E. title = Role of endothelial cell survival and death signals in angiogenesis date = 1999 pages = extension = .txt mime = text/plain words = 9984 sentences = 559 flesch = 35 summary = There is now convincing evidence that regulated patterns of endothelial cell survival and death, a process known as apoptosis, play a central role in the periodic remodeling of the vasculature, and in the timely evolution and regression of angiogenic responses. In this review we discuss the current evidence suggesting a role for inducers and inhibitors of angiogenesis as well as other mediators that modify endothelial cells functions in the survival and death of endothelial cells. Events that govern the survival and death of endothelial cells have emerged as major factors that contribute to angiogenic responses during embryonic development, in the maintenance of organ and tissue homeostasis in adult organisms, and in pathological conditions such as tumor development. Enhanced activity of protein kinase C was associated with the ability of bFGF to protect endothelial cells against apoptosis induced by growth factor deprivation [170] or ionizing radiation in vitro and in vivo [170±172]. Vascular Endothelial Growth Factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression cache = ./cache/cord-006610-me8rhkcg.txt txt = ./txt/cord-006610-me8rhkcg.txt === reduce.pl bib === id = cord-000324-to4g9he9 author = Spentzas, Thomas title = Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus date = 2011-01-25 pages = extension = .txt mime = text/plain words = 5297 sentences = 245 flesch = 37 summary = title: Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus In a sepsis simulation model, we tested whether the anesthetic ketamine inhibits the macrophage TNF response to antibiotic-exposed CA-MRSA bacteria via its antagonism of N-methyl-D-aspartate (NMDA) receptors. The NMDA inhibitors, MK-801 and APV, also suppressed macrophage TNF secretion after stimulation with either of the antibiotic-exposed CA-MRSA isolates, and the effect was not additive or synergistic with ketamine. The mechanisms responsible for the anti-inflammatory effects of ketamine are not known [22] [23] [24] [25] .The present study examined the hypothesis that ketamine could suppress macrophage TNF production in response to whole bacteria, in this case clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). The addition of ketamine (100 μΜ) to macrophage cell cultures inhibited TNF secretion in response to vancomycin-or daptomycin-exposed CA-MRSA isolates ( Figure 2) . cache = ./cache/cord-000324-to4g9he9.txt txt = ./txt/cord-000324-to4g9he9.txt === reduce.pl bib === id = cord-005664-n4xv247l author = Plötz, Frans B. title = Mechanical ventilation alters the immune response in children without lung pathology date = 2002-01-15 pages = extension = .txt mime = text/plain words = 3292 sentences = 182 flesch = 41 summary = In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-α and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. The major finding of the present study is that exposing infants with normal lung function to 2 h of volatile anesthetics, mechanical ventilation, and cardiac catheterization is associated with remarkable changes in immune responses. We observed a proinflammatory response in the lungs with a significant increase in TNF-α, while antiinflammatory cytokine concentrations in tracheal aspirates remained virtually unchanged, just above the detection level. cache = ./cache/cord-005664-n4xv247l.txt txt = ./txt/cord-005664-n4xv247l.txt === reduce.pl bib === id = cord-002209-xs6qigg4 author = Kıray, Hülya title = The multifaceted role of astrocytes in regulating myelination date = 2016-09-17 pages = extension = .txt mime = text/plain words = 7509 sentences = 355 flesch = 35 summary = In experimental allergic encephalomyelitis (EAE), a widely used animal model of MS, where demyelination is induced by myelin antigens, administered together with adjuvant that contains bacterial components (Traugott and Lebon, 1988; Tsukada et al., 1991; Villarroya et al., 1996) , GFAP expression was seen on more numerous and much larger astrocytic processes in chronic lesions compared to normal appearing white matter (Webster et al., 1985; Eng et al., 1971) . The milder "activated" astrocytes can secrete a range of factors including; neurotrophic factors, growth factors, and cytokines that will stimulate re/myelination by promoting neuronal survival, neurite outgrowth, neurogenesis, and/ or oligodendrocyte precursor cell (OPC) survival, proliferation, and/or maturation. Conversely astrocytes that tend to have a more severe "reactive" phenotype, possibly induced by proinflammatory cytokines/CNS tissue damage, may secrete cytokines and chemokines that lead to myelin and oligodendrocyte damage in vitro, suppress remyelination, delay disease recovery in experimental autoimmune encephalomyelitis (EAE), and suppress myelination in myelinating embryonic rat mixed spinal cord cultures. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury cache = ./cache/cord-002209-xs6qigg4.txt txt = ./txt/cord-002209-xs6qigg4.txt === reduce.pl bib === id = cord-001293-dfaxj3bv author = Cavaillon, Jean-Marc title = Is boosting the immune system in sepsis appropriate? date = 2014-03-24 pages = extension = .txt mime = text/plain words = 6238 sentences = 315 flesch = 33 summary = In response to the failure of therapies aiming to target either the up-stream microbial activators or the effector molecules of the inflammatory cascade, a new concept has emerged of boosting the immune system to counter immunosuppression that develops in patients who survive the initial, hyperinflammatory period of sepsis [1] . One can conjecture that systemic treatment with IL-7 may act in undesired places, as illustrated by the following: IL-7 worsens graft-versus-host-induced tissue inflammation [81] ; favors inflammation in colitis [82] , contributes to arthritis severity [83] ; upregulates chemokines, IFNγ, macrophage recruitment, and lung inflammation [84] ; and, finally, increases production of inflammatory cytokines by monocytes and T cells [85] . Not only are PD-1-deficient mice markedly protected from the lethality of sepsis, accompanied by a decreased bacterial burden and suppressed inflammatory cytokine response [98] , but also blockade of PD-1 or PD-L1 improves survival in a murine model of sepsis, reverses immune dysfunction, inhibits lymphocyte apoptosis, and attenuates organ dysfunction [99] [100] [101] . cache = ./cache/cord-001293-dfaxj3bv.txt txt = ./txt/cord-001293-dfaxj3bv.txt === reduce.pl bib === id = cord-005983-2ascbu62 author = Eigler, A. title = Suppression der Synthese des Tumornekrosefaktors date = 2001 pages = extension = .txt mime = text/plain words = 2378 sentences = 302 flesch = 41 summary = Klinische Studien aus den vergangenen 5 Jahren belegen die zentrale Rolle des Tumornekrosefaktors (TNF) im pathophysiologischen Geschehen der rheumatoiden Arthritis und des Morbus Crohn.Die vorliegende Arbeit gibt einen Überblick über die Regulation der Synthese und die vielfältigen Wirkungen dieses Zytokins.So wurden erhöhte TNF-Konzentrationen bei verschiedenen infektiösen und entzündlichen Erkrankungen sowie in Verbindung mit speziellen Therapien nachgewiesen.Darauf aufbauend werden experimentelle therapeutische Strategien zur Hemmung der TNF-Bildung dargestellt. In den folgenden Abschnitten wird näher auf Strategien zur Hemmung der TNF-Synthese eingegangen, die im Tierexperiment oder schon beim Menschen in klinischen Studien untersucht worden sind. Die entzündungshemmende Wirkung von cAMP-erhöhenden Substanzen wird jedoch nicht nur über eine Hemmung der TNF-Synthese vermittelt. Weiterhin konnte durch die Therapie mit Rolipram die Suppression der TNF-Synthese und ein Überlebensvorteil in einem Rattenmodell des ARDS gezeigt werden [40] . The specific type IV phosphodiesterase inhibitor rolipram suppresses tumor necrosis factor-α production by human mononuclear cells cache = ./cache/cord-005983-2ascbu62.txt txt = ./txt/cord-005983-2ascbu62.txt === reduce.pl bib === id = cord-002079-jne14jqf author = MacParland, Sonya A. title = Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date = 2016-05-27 pages = extension = .txt mime = text/plain words = 7182 sentences = 388 flesch = 48 summary = Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. These data demonstrate that certain inflammatory stimuli (TNF-␣ and LPS), as well as ischemic injury, but not other cytokines (IL-6 and IL-10) can lead to enhanced hepatocyte USP18 expression and thereby inhibit IFN signaling. Huh7.5 cells and primary murine hepatocytes were treated with IFN-␣ (100 U/ml), TNF-␣ (20 ng/ml), LPS (100 ng/ml), IL-6 (100 ng/ml), or IL-10 (10 ng/ ml) over a 24-h time course, and USP18 expression was determined by quantitative PCR (qPCR) as previously described (8, 9) . cache = ./cache/cord-002079-jne14jqf.txt txt = ./txt/cord-002079-jne14jqf.txt === reduce.pl bib === id = cord-013183-t25gecuw author = Beloumi, Dhekra title = Inflammatory Correlated Response in Two Lines of Rabbit Selected Divergently for Litter Size Environmental Variability date = 2020-09-01 pages = extension = .txt mime = text/plain words = 3575 sentences = 205 flesch = 49 summary = The aim of this study was to evaluate the inflammatory response in the two lines of the experiment, in order to analyse the effect of selection on susceptibility to diseases after challenging to stressful situations, such as 24 h after the first delivery. The line selected for litter size heterogeneity (the high line) showed lower white blood leukocyte count (WBC; −0.87 × 10(3)/µL), lower percentage of basophils (−0.11%), higher concentration of TNF-α (+13.8 pg/mL), and greater concentration of CRP (+38.1 µg/mL) than the line selected for litter size homogeneity (the low line). The objective of this study was to evaluate the inflammatory response in the two lines of the divergent selection experiment for litter size environmental variance, in order to analyse the effect of selection on susceptibility to diseases after stressful situations, such as 24 h after the first delivery. cache = ./cache/cord-013183-t25gecuw.txt txt = ./txt/cord-013183-t25gecuw.txt === reduce.pl bib === id = cord-004919-d7tilk8v author = Baker, Rahaf title = Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab date = 2018-12-07 pages = extension = .txt mime = text/plain words = 1869 sentences = 105 flesch = 42 summary = MAS is a potentially fatal syndrome that can present in patients with inflammatory conditions and is considered to be similar to hemophagocytic lymphohistiocytosis (HLH) [1, 2] . The most consistent diagnosis for our patient was MAS, as he had high persistent fevers without an infectious cause, lymphopenia and anemia, marked hyperferritinemia, hypertriglyceridemia, splenomegaly, and the presence of hemophagocytes on bone marrow biopsy. It is plausible that adalimumab triggered MAS in our patient as he presented at 2.5 months after initiation of adalimumab, which is consistent with the timeline from other case reports, and he had no obvious infection. Macrophage activation syndrome associated with etanercept in a child with systemic onset juvenile idiopathic arthritis Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis Visceral leishmaniasis and macrophagic activation syndrome in a patient with rheumatoid arthritis under treatment with adalimumab Possible macrophage activation syndrome following initiation of adalimumab in a patient with adult-onset still's disease cache = ./cache/cord-004919-d7tilk8v.txt txt = ./txt/cord-004919-d7tilk8v.txt === reduce.pl bib === id = cord-006518-al94gxjw author = Calder, Philip C. title = n−3 Fatty acids, inflammation, and immunity— Relevance to postsurgical and critically III patients date = 2004 pages = extension = .txt mime = text/plain words = 10029 sentences = 518 flesch = 43 summary = More recent studies showed that EPA did not induce TNF-α, IL-1β, or IL-1α (68) or IL-6 (69) in osteoblasts, and even countered the upregulating effect of arachidonic acid (68) ; that EPA and DHA could totally abolish cytokine-induced up-regulation of TNF-α, IL-1α, and IL-1β in cultured bovine chondrocytes and in human osteoarthritic cartilage explants (93, 94) ; and that EPA or fish oil inhibited endotoxin-induced TNF-α production by monocytes (111) (112) (113) (114) . Animal feeding studies with fish oil support the observations made in cell culture with respect to the effects of long-chain n-3 FA on NFκB activation and inflammatory cytokine production. Several studies in humans involving supplementation of the diet with fish oil have demonstrated decreased production of TNF-α, IL-1β, and IL-6 by endotoxin-stimulated monocytes or mononuclear cells (a mixture of lymphocytes and monocytes) (80) (81) (82) 119) . cache = ./cache/cord-006518-al94gxjw.txt txt = ./txt/cord-006518-al94gxjw.txt === reduce.pl bib === id = cord-006770-m5wqk6rh author = Rook, Graham A. W. title = Evaluation of TNF as antiviral, antibacterial and antiparasitic agent date = 1991 pages = extension = .txt mime = text/plain words = 4564 sentences = 212 flesch = 43 summary = On the other hand such antibody had little effect if given on day 3 or later, suggesting that the protective role of TNF is mostly during the early phase of the infection. Effect of recombinant tumour necrosis factor on acute infection in mice with toxoplasma gondii or Trypanosoma cruzi Protective effects of tumor necrosis factor in experimental LegioneUa pneumophila infections of mice via activation of PMN function Production of tumor necrosis factor alpha and interteukin 1 beta by monocytic cells infected with human immunodeficiency virus The in vitro antiviral activity of tumor necrosis factor (TNF) in WISH cells is mediated by IFN-beta induction Human tumour necrosis factor alpha kills herpesvirus-infected, but not normal cells Cytocidal effect of tumor necrosis factor on cells chronically infected with human immunodeficiency virus (HIV): enhancement of HIV replication Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone cache = ./cache/cord-006770-m5wqk6rh.txt txt = ./txt/cord-006770-m5wqk6rh.txt === reduce.pl bib === id = cord-003013-h8txbd3p author = Kim, Sena title = Differential Regulation of Toll-Like Receptor-Mediated Cytokine Production by Unfolded Protein Response date = 2018-04-24 pages = extension = .txt mime = text/plain words = 3706 sentences = 205 flesch = 35 summary = Under ER stress, unfolded protein response (UPR) signaling pathways participate in upregulating inflammatory cytokine production via NF-kappaB, MAPK, and GSK-3β. Toll-like receptor (TLRs) can recognize pathogenassociated molecular patterns (PAMPs) and dangerassociated molecular patterns (DAMPs) and induce TLRmediated intracellular signaling cascades to eliminate the pathogens through the production of proinflammatory cytokines including TNF-α, IL-6, IL-1β, and IL-8, but its uncontrolled activation can damage the host [9] . ER stress has been shown to regulate proinflammatory cytokine production, which are mediated by TLR signaling cascade components such as NF-kappaB, MAPK, and GSK-3β. In addition, ER stress shares TLR-mediated signaling components with pro-and anti-inflammatory cytokine productions, leading to the activation of NF-kappaB and MAPKs. The XBP1 deletion or chemical chaperone treatment in macrophages alleviates proinflammatory cytokine production by LPS. Toll-like receptor-mediated activation of intracellular signaling pathways results in increased production of proinflammatory cytokines including TNF-α, IL-6, and IL-1β. Endoplasmic reticulum stress-induced IRE1α activation mediates cross-talk of GSK-3β and XBP-1 to regulate inflammatory cytokine production cache = ./cache/cord-003013-h8txbd3p.txt txt = ./txt/cord-003013-h8txbd3p.txt === reduce.pl bib === id = cord-002119-kl431ev6 author = Garcia, Elisa title = Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury date = 2016-06-23 pages = extension = .txt mime = text/plain words = 13445 sentences = 687 flesch = 41 summary = Specific inflammatory cytokines such as TNF , IL-1, and IL-6 are synthetized by various cells in the CNS and are known as mediators of the peripheral immune response 8 [118, 192] IL-4 (i) High levels 24 h AI, concentrations remain during 7 days and decrease 3 days AI (i) Neuroinflammatory regulation in various pathological conditions (ii) Confers regenerative properties to macrophages (iii) Controls free radical production in peripheral macrophages and microglia [166, [193] [194] [195] [196] [197] [198] [199] IL-13 (i) Detected 1 day AI (i) Macrophage activation onto M2 phenotype [166, 199] IP-10/CXCL10 (i) Expressed locally 30 [200, [205] [206] [207] Mediators of Inflammation 9 [200, [205] [206] [207] MCP1/CCL2 (i) Detected from 1 h AI with PL at 24 h and remains low up to 24 days AI (i) Macrophage and PMN infiltration mediator [106, 184, 200, 205, 206] min: minutes; AI: after injury; PL: peak levels. cache = ./cache/cord-002119-kl431ev6.txt txt = ./txt/cord-002119-kl431ev6.txt === reduce.pl bib === id = cord-007613-g4s0v8ra author = Rimstad, Espen title = Cloning, expression and characterization of biologically active feline tumour necrosis factor-α date = 2000-03-10 pages = extension = .txt mime = text/plain words = 4664 sentences = 265 flesch = 58 summary = To assure that stimulated macrophage mRNA was the actual source for cDNA, cDNA derived by reverse transcription of mRNA from unstimulated macrophage cultures, as well as feline genomic DNA, were extracted and used as targets in separate and parallel PCRs. The amplified fragments generated by both the P 1 /P3 and P2/P3 primers were separately cloned into the plasmid vector pCRI1 (TA-cloning kit, Invitrogen), and the nucleotide sequences were determined by conventional dideoxy sequencing of both strands. Although some variation was evident between the four individual donor cats, rfTNF-a induced a dose related increase of IG2R and MHC class II antigen expression on the cell surface of in vitro stimulated feline PMBCs (Fig. 6 ) . Tumor necrosis factor a induces expression of human immunodeticiency virus in a chronically infected T-cell clone Tumor necrosis factor a induces proteins that bind specifically to kB-like enhancer elements and regulate interleukin 2 receptor a-chain gene expression in primary human T-lymphocytes cache = ./cache/cord-007613-g4s0v8ra.txt txt = ./txt/cord-007613-g4s0v8ra.txt === reduce.pl bib === id = cord-003686-1pfk4qve author = Kaneko, Naoe title = The role of interleukin-1 in general pathology date = 2019-06-06 pages = extension = .txt mime = text/plain words = 9464 sentences = 514 flesch = 38 summary = The majority of NOD-like receptors such as NLRP1, NLRP3, NLRC4, NLRP6, and NLRP12 can interact with apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and caspase-1, and the resulting complex is a sensor of cell injury called "inflammasome", an interleukin (IL)-1β-processing platform that plays a crucial role in IL-1β maturation and secretion from cells. NLRP3 inflammasomes have also been reported to be involved in low-grade subclinical inflammation induced by chronic exposure to high levels of free fatty acids and glucose, leading to increased apoptosis and impaired insulin secretion of β-cells in obese type 2 diabetes mellitus (T2D) patients [102] [103] [104] . Canakinumab and anakinra were also effective for patients with Schnitzler syndrome, an adult-onset autoinflammatory disease characterized by focal urticaria and systemic inflammation including fever with bone and muscle pain, in the first placebo-controlled study, and several clinical trials are currently ongoing [186] [187] [188] [189] . cache = ./cache/cord-003686-1pfk4qve.txt txt = ./txt/cord-003686-1pfk4qve.txt === reduce.pl bib === id = cord-006828-i88on326 author = nan title = Abstracts DGRh-Kongress 2013 date = 2013-09-15 pages = extension = .txt mime = text/plain words = 30772 sentences = 2576 flesch = 52 summary = Comparing gene expression profiles of yellow fever immunized individuals and active SLE patients it was possible to identify a "common" and an "autoimmune-specific" IFN signature. The inflammatory and profibrotic effects upon Aab stimulation in vitro, and their associations with clinical findings suggest a role for autoantibody-mediated activation of immune cells mediated through the AT1R and ETAR in the pathogenesis or even the onset of the disease. This study was aimed to investigate the humoral and cellular immune response to VZV including assessment of IgG-anti-VZV avidity and VZV-specific reactivity of lymphocytes in RA (n=56) or JIA patients (n=75) on different treatments, including biologic agents, such as anti-tumor-necrosis-factor(TNF)-alpha or anti-interleukin-6 (IL-6) receptor inhibition (tocilizumab), compared to 37 healthy adults (HA) and 41 children (HC). Production of cytokines by B cells in response to TLR9 stimulation inversely correlates with disease activity in SLE-patients cache = ./cache/cord-006828-i88on326.txt txt = ./txt/cord-006828-i88on326.txt === reduce.pl bib === id = cord-007858-1ijxilpb author = Xu, G.L. title = Attenuation of acute lung injury in mice by oxymatrine is associated with inhibition of phosphorylated p38 mitogen-activated protein kinase date = 2005-04-08 pages = extension = .txt mime = text/plain words = 4055 sentences = 228 flesch = 55 summary = Furthermore, pretreatment with oxymatrine significantly alleviated oleic acid-induced lung injury accompanied by reduction of lung index and wet-to-dry weight ratio, decreases in serum TNF-α level and inhibition of phosphorylated p38 MAPK. These findings suggest that oxymatrine has a beneficial effect on acute lung injury induced by oleic acid in mice and may inhibit the production of proinflammatory cytokine, TNF-α, by means of the inhibition of p38 MAPK. Light microscopic findings in the lung at 6 h after oleic acid injection demonstrated a marked lung injury resembling those seen in lung of patients with ALI/ARDS, represented by prominent atelectasis, intraalveolar and interstitial patchy hemorrhage, edema, thickened alveolar septum, formation of hyaline membranes and the existence of inflammatory cells in alveolar spaces (Fig. 1A) , which were not observed in the control group (Fig. 1B) . Effect of oxymatrine on serum TNF-␣ level in mice with lung injury induced by oleic acid. cache = ./cache/cord-007858-1ijxilpb.txt txt = ./txt/cord-007858-1ijxilpb.txt === reduce.pl bib === id = cord-007621-rapinodd author = Vidovic, Maria title = Induction and regulation of class II major histocompatibility complex mRNA expression in astrocytes by interferon-γ and tumor necrosis factor-α date = 2002-11-13 pages = extension = .txt mime = text/plain words = 6680 sentences = 365 flesch = 57 summary = Previous data from this laboratory had shown that the cytokine tumor necrosis factor-α (TNF-α) enhances IFN-γ-mediated class II antigen expression on astrocytes. To determine the steady-state level of mRNA for class II, Northern blot analysis was performed using a eDNA probe for murine class Ii genes (E-a), with total RNA isolated from cultured astrocytes. The duration of protein synthesis required to allow expression of the class II MHC gene in astrocytes was examined in cells that were pretreated with IFN-y or IFN-7/TNF-a for different lengths of time prior to the addition of CHX. In this study we have shown that primary neonatal rat astrocytes, upon stimulation with IFN-~,, express mRNA transcripts for class II MHC genes, and that TNF-a enhances the expression of IFN-~,-induced class II mRNA. The expression of class II mRNA was completely inhibited when CHX was included with IFN-~, and IFN-'t/TNF-~ treatment, indicating that newly synthesized protein is required for astrocyte class II MHC gene expression. cache = ./cache/cord-007621-rapinodd.txt txt = ./txt/cord-007621-rapinodd.txt === reduce.pl bib === id = cord-005872-w1x1i0im author = Volk, T. title = Endothelium function in sepsis date = 2000 pages = extension = .txt mime = text/plain words = 8871 sentences = 463 flesch = 29 summary = Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. S. aureus has been reported to directly infect human umbilical vein endothelial cells (HUVEC) thereby inducing secretion of cytokines and functional upregulation of adhesion molecules [2] . Infection and activation of endothelial cells by Listeria monocytogenes is believed to be a critical component of the pathogenesis of this disease and includes ceramide generation, transcription factor activation and increases in adhesion molecule expression on HUVEC [11] . E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation cache = ./cache/cord-005872-w1x1i0im.txt txt = ./txt/cord-005872-w1x1i0im.txt === reduce.pl bib === id = cord-009326-dvhkk405 author = Lee, Jae Min title = Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation date = 2020-03-14 pages = extension = .txt mime = text/plain words = 6438 sentences = 359 flesch = 51 summary = title: Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation PRE inhibited TNF-α-induced NF-κB transcriptional activity in the NF-κB luciferase assay and pro-inflammatory genes' expression by blocking phosphorylation of IκB and NF-κB in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-κB phosphorylation and pro-inflammatory genes' expression. To investigate the effects of PRE on inflammation, we first tested NF-κB transcriptional activity of TPRE because NF-κB is an essential regulator of pro-inflammatory response ( Figure S1 ). Together, these results strongly suggest that PRE suppresses TNF-α-mediated pro-inflammatory gene expression by activating AMPK. Together, these results strongly suggest that PRE suppresses TNF-α-mediated pro-inflammatory gene expression by activating AMPK. cache = ./cache/cord-009326-dvhkk405.txt txt = ./txt/cord-009326-dvhkk405.txt === reduce.pl bib === id = cord-013366-sbdtpsz6 author = Ramírez-Pérez, Sergio title = Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor date = 2020-09-21 pages = extension = .txt mime = text/plain words = 5749 sentences = 283 flesch = 45 summary = Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both proand anti-inflammatory cytokines. The chemical molecule ST2825 acts as an inhibitor of MyD88 dimerisation and its activity has been demonstrated through the inhibition of TLR9-dependent CpG-regulated signalling, and inhibition of IL-12, IL-1β, IL-6 and tumor necrosis factor alpha (TNF-α) expression in LPS-stimulated RAW 264.7 cells [19] [20] [21] [22] . The present study shows that the specific inhibition of critical components in the IL-1 signalling pathway is not enough to avoid the secretion of inflammatory mediators, the above suggests that various MyD88-independent mechanisms could regulate the production of cytokines in PBMC. cache = ./cache/cord-013366-sbdtpsz6.txt txt = ./txt/cord-013366-sbdtpsz6.txt === reduce.pl bib === id = cord-023402-8qfmo6rq author = Reinholdt, J. title = Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype‐Specific Human Monoclonal IgA1 Antibodies date = 2008-06-28 pages = extension = .txt mime = text/plain words = 17011 sentences = 882 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023402-8qfmo6rq.txt txt = ./txt/cord-023402-8qfmo6rq.txt === reduce.pl bib === id = cord-006444-eq56zhtd author = nan title = Abstracts of oral presentations and posters date = 1993 pages = extension = .txt mime = text/plain words = 40668 sentences = 2121 flesch = 53 summary = The results from ongoing preclinical studies continue to confirm the broad spectrum of biological activities possessed by rhiL-1 1 in vitro and suggest this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation. We performed a phase H trial to assess the ability of G-CSF -mobilized PBPC to rapidly and completely restore hemopeiesis after high dose chemotherapy in the absence of bone marrow infusions, with selection for PBPC-only infusions based on yield of granulocyte -macrophage colony -forming cells (GM-CFC) after G-CSF treatment. Our approach for high-dose (HD) chemotherapy is to first treat patients eligible for dose intensification with a standard dose chemotherapy (VIP: VP26 = etoposide: 500 mg/m 2, ifosfamide: 4 g/m 2, cis-platinum: 50 mg/m 2) followed by the application of colony stimulating factors (G-CSF, GM-CSF or IL-3 + GM-CSF) in order to combine a regimen with broad anti-tumor activity with the recruitment of peripheral blood progenitor cells (PBPCs). cache = ./cache/cord-006444-eq56zhtd.txt txt = ./txt/cord-006444-eq56zhtd.txt === reduce.pl bib === id = cord-023393-8nye3nc8 author = Krarup, A. title = Mannan‐Binding Lectin, L‐Ficolin and H‐Ficolin Selectively Binds to Different Bacteria date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16820 sentences = 864 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023393-8nye3nc8.txt txt = ./txt/cord-023393-8nye3nc8.txt === reduce.pl bib === id = cord-023373-6wh1kb3p author = Melchjorsen, J. title = Differential Requirements for Toll‐Like Receptor Signalling for Induction of Chemokine Expression by Herpes Simplex Virus and Sendai Virus date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16841 sentences = 866 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023373-6wh1kb3p.txt txt = ./txt/cord-023373-6wh1kb3p.txt === reduce.pl bib === id = cord-017520-r786yd6i author = Huber-Lang, Markus title = Inflammatory Changes and Coagulopathy in Multiply Injured Patients date = 2015-05-14 pages = extension = .txt mime = text/plain words = 7032 sentences = 356 flesch = 34 summary = Severe tissue trauma leads to an early activation of several danger recognition systems, including the complement and the coagulation system, often resulting in an overwhelming almost synchronic proand anti-inflammatory response of the host. Although the immune response is associated with beneficial effects at the site of injury including the elimination of exogenous and endogenous danger molecules as well as the initiation of regenerative processes, an exaggerated systemic inflammatory response significantly contributes to posttraumatic complications such as multiple organ failure (MOF) and early death. The steps of an inflammatory reaction to trauma involve fluid phase mediators (cytokines, chemokines, coagulation-and complement activation products, oxygen radicals, eicosanoids, and nitric oxide (NO)) and cellular effectors (neutrophils, monocytes/macrophages, and endothelial cells) that translate the trauma-induced signals into cellular responses. cache = ./cache/cord-017520-r786yd6i.txt txt = ./txt/cord-017520-r786yd6i.txt === reduce.pl bib === id = cord-023421-1d1gf7az author = Sønder, S. U. S. title = Monitoring Patients Treated with Type 1 Interferons: Antiviral versus MxA Induction Assays date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16866 sentences = 873 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023421-1d1gf7az.txt txt = ./txt/cord-023421-1d1gf7az.txt === reduce.pl bib === id = cord-015910-d9gxew91 author = Grimble, Robert F. title = The Interaction Between Nutrition and Inflammatory Stress Throughout the Life Cycle date = 2005 pages = extension = .txt mime = text/plain words = 15205 sentences = 709 flesch = 40 summary = Binding of the transcription factors is implicated in activation of a wide range of genes associated with inflammation and the immune response, including those encoding cytokines, cytokine receptors, cell adhesion molecules, acute-phase proteins, and growth factors (Schreck, Rieber, & Baeurerle, 1991) (Fig. 4 ) . While inflammation may be exerting deleterious effects most obviously in patients, people on the borderline of health and disease living in the general population Table 4 Nutrients Commonly Used in Immunonutrient Supplements and Their Potential Mode of Action • n-3 polyunsaturated fatty acids: act as anti-inflammatory agents and reverse immunosuppression • Sulfur amino acids and their precursors: enhance antioxidant status via GSH synthesis • Glutamine: nutrient for immune cells, improves gut barrier function, precursor for GSH • Arginine: stimulates nitric oxide and growth hormone production, improves helper T-cell numbers • Nucleotides: RNA and DNA precursors, improve T-cell function may also require nutritional modulation of ongoing inflammatory processes. cache = ./cache/cord-015910-d9gxew91.txt txt = ./txt/cord-015910-d9gxew91.txt === reduce.pl bib === id = cord-023431-zjyrhlxn author = Sigmundsdóttir, H. title = Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16867 sentences = 869 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023431-zjyrhlxn.txt txt = ./txt/cord-023431-zjyrhlxn.txt === reduce.pl bib === id = cord-020643-0yzkqykg author = Müller-Werdan, U. title = Schock date = 2006 pages = extension = .txt mime = text/plain words = 30645 sentences = 4322 flesch = 46 summary = Auch dass nichtinfektiöse Noxen (Trauma, Pankreatitis, herzchirurgische Operationen mit der Herz-Lungen-Maschine) zu einem ganz ähnlichen klinischen Bild wie bei bakteri-ell ausgelöster Sepsis und septischem Schock führen können, spricht für eine mehr oder weniger gemeinsame Zytokin-/Mediatorendstrecke als verantwortliche Schädigungskaskade sowohl bei infektiösen als auch bei nichtinfektiösen (SIRS, . Eine Ausnahme von dieser Regel stellt die Hirndurchblutung dar, die in der Sepsis weiterhin die Fähigkeit zur Autoregulation beibehält: Bei Patienten mit Sepsis ist die Hirndurchblutung bereits vor der Ausbildung des Schockzustandes um ein Drittel reduziert, wobei diese Durchblutungseinschränkung jedoch nicht als Ursache der septischen Enzephalopathie angesehen wird. Im Koronargefäßsystem fällt dagegen der Widerstand noch stärker ab als in den anderen Organen und demzufolge ist die Koronarperfusion bei Patienten mit septischem Schock sogar häufi g erhöht (Dhainaut et al. Die Messung des zentralen Venendrucks ist bei kritisch Kranken, insbesondere Schockpatienten, für das hämodynamische Monitoring normalerweise nicht genügend, eine Abschätzung der linksventrikulären Vorlast kann damit nicht ausreichend sicher durchgeführt werden, ebenso wenig wie mit der klinischen Einschätzung allein. cache = ./cache/cord-020643-0yzkqykg.txt txt = ./txt/cord-020643-0yzkqykg.txt === reduce.pl bib === id = cord-015147-h0o0yqv8 author = nan title = Oral Communications and Posters date = 2014-09-12 pages = extension = .txt mime = text/plain words = 73711 sentences = 3862 flesch = 43 summary = Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis. cache = ./cache/cord-015147-h0o0yqv8.txt txt = ./txt/cord-015147-h0o0yqv8.txt === reduce.pl bib === id = cord-017639-wtc8bml5 author = El-Radhi, A. Sahib title = Pathogenesis of Fever date = 2019-01-02 pages = extension = .txt mime = text/plain words = 5141 sentences = 346 flesch = 44 summary = The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. • Cytokines are proteins produced throughout the body, mainly by activated macrophages, monocytes and T cells to regulate the immune responses within the body, control inflammatory and haematopoietic processes and may induce fever. Pro-inflammatory cytokines (e.g. IL-1, IL-6, TNF-α, INF-γ, granulocytes-macrophages colony stimulating factor, GM-CSF) are responsible for initiating an effective defence against exogenous organisms (e.g. activating neutrophils). • Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. • Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. cache = ./cache/cord-017639-wtc8bml5.txt txt = ./txt/cord-017639-wtc8bml5.txt === reduce.pl bib === id = cord-023375-x4p187u7 author = Alitalo, A. title = Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi date = 2008-06-28 pages = extension = .txt mime = text/plain words = 17059 sentences = 877 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023375-x4p187u7.txt txt = ./txt/cord-023375-x4p187u7.txt === reduce.pl bib === id = cord-004879-pgyzluwp author = nan title = Programmed cell death date = 1994 pages = extension = .txt mime = text/plain words = 81677 sentences = 4465 flesch = 51 summary = Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. cache = ./cache/cord-004879-pgyzluwp.txt txt = ./txt/cord-004879-pgyzluwp.txt === reduce.pl bib === id = cord-018764-02l423mk author = Clark, Ian A. title = The molecular basis of paediatric malarial disease date = 2007 pages = extension = .txt mime = text/plain words = 10008 sentences = 485 flesch = 35 summary = The influence of inflammatory cytokines on cellular function offers a molecular framework to explain the multiple clinical syndromes that are observed during acute malarial illness, and provides a fresh avenue of investigation for adjunct therapies to ameliorate the malarial disease process. The presence of hyperlactataemia, hypoglycaemia, and metabolic acidosis, all three consistent with a patient being forced to rely on anaerobic glycolysis for energy production, have provided a consensus that hypoxia is central to disease pathogenesis in falciparum malaria. Another inflammatory cytokine, macrophage inhibitory factor (MIF) that is increased in malaria, and induced by TNF, has been shown to cause dyserythropoiesis in in vitro studies on bone marrow cells [95, 96] . Although the sepsis world now discusses several origins for the lactate increase, including inflammation-induced mitochondrial dysfunction [97] , in falciparum malaria it is still generally attributed to a reduced oxygen supply, mostly through microvascular occlusion by sequestered parasitised erythrocytes [121] . cache = ./cache/cord-018764-02l423mk.txt txt = ./txt/cord-018764-02l423mk.txt === reduce.pl bib === id = cord-021266-afs9eb40 author = El Gendy, Fady M. title = The role of Tumor necrosis factor alpha −308 G>A promoter polymorphism in pediatric community acquired pneumonia date = 2020-02-10 pages = extension = .txt mime = text/plain words = 3756 sentences = 222 flesch = 50 summary = Our objective was to evaluate the association of TNF-α gene −308 G>A polymorphism with susceptibility to, and severity of, community-acquired pneumonia (CAP). We found no significant association of alleles or genotypes with any indicators of CAP severity, including clinical severity scores, but we were not able to assess the influence of TNF-α polymorphism on mortality since none of our patients died. Consistent with our findings, genotyping of 77 children with respiratory syncytial virus infection revealed no association of TNF-α −308 G>A polymorphism with any of the clinical outcomes, including severity scores of lower respiratory illness, oxygen saturation, lengths of oxygen supplementation, intensive care unit (ICU) and hospital stays, and the presence or absence of pneumonia and otitis media [25] . However, another study of 277 Chinese adult patients with severe pneumonia-induced sepsis found that TNF-α "A" allele increased the risk of septic shock (OR = 4.28). cache = ./cache/cord-021266-afs9eb40.txt txt = ./txt/cord-021266-afs9eb40.txt === reduce.pl bib === id = cord-103625-p55ew8w7 author = Ramana, Chilakamarti V. title = Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date = 2020-08-14 pages = extension = .txt mime = text/plain words = 3320 sentences = 217 flesch = 47 summary = Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Furthermore, Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients. In this study, transcription factor profiling in interferon-mediated gene expression data sets and RT-PCR revealed that Egr-1 was rapidly induced by IFN-α/β and TLR ligands in multiple cell types. Respiratory pathogens including coronaviruses (SARS-CoV-1 and 2) and influenza viruses regulated the expression of Egr-1 in human lung cell lines and in lung biopsies and peripheral blood cells of COVID-19 patients, These studies suggest that the regulation of Egr-1 may play an important role in the antiviral response and inflammatory disease. cache = ./cache/cord-103625-p55ew8w7.txt txt = ./txt/cord-103625-p55ew8w7.txt === reduce.pl bib === id = cord-023441-q83y12sk author = Draborg, H. title = Recominant Expression and Immunological Characterization of House Dust Mite Allergen Der P 1 date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16905 sentences = 868 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023441-q83y12sk.txt txt = ./txt/cord-023441-q83y12sk.txt === reduce.pl bib === id = cord-023392-axd0901z author = Hansen, T. K. title = Association between Mannose‐Binding Lectin and Vascular Complications in Type 1 Diabetes date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16944 sentences = 875 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023392-axd0901z.txt txt = ./txt/cord-023392-axd0901z.txt === reduce.pl bib === id = cord-016168-3hyb9stq author = nan title = Pathogenesis of Fever date = 2009 pages = extension = .txt mime = text/plain words = 4067 sentences = 272 flesch = 45 summary = • Fever (pyrexia) is a regulated body temperature above the normal range occurring as a result of IL-1-mediated elevation of the hypothalamic set point. • Cytokines are proteins produced throughout the body, mainly by monocytes, macrophages, and T cells to regulate the immune responses within the body and control inflammatory and haematopoietic processes and may induce fever. • Pro-inflammatory cytokines (IL-1, IL-6, TNF-α, INF-γ, granulocyte-macrophage colony-stimulating factor, GM-CSF) are responsible for initiating an effective defense against exogenous organisms. Other mechanisms to initiate fever include the following: Some endotoxins, produced by bacteria, act directly on the hypothalamus to alter the set point. Mechanisms by which viruses may produce fever include direct invasion of macrophages, immunological reaction to viral components involving antibody formation, induction by INF, and necrosis of cells by viruses. Increased TNF production in Kawasaki disease may play a role in the immune activation and damage to vascular endothelial cells occurring in the disease. cache = ./cache/cord-016168-3hyb9stq.txt txt = ./txt/cord-016168-3hyb9stq.txt === reduce.pl bib === id = cord-023372-ft8cp9op author = Rahman, Q. K. title = The Immunomodulatory Effect of Heat Shock Protein 70: Immunization with a DNA Construct Based on the Malarial Antigen Fused with a Fragment of HSP 70 Primes for a Th‐1 Type of Response date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16863 sentences = 874 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023372-ft8cp9op.txt txt = ./txt/cord-023372-ft8cp9op.txt === reduce.pl bib === id = cord-022631-s4n24xij author = Jonsson, M. V. title = Germinal Centres in Primary Sjögren's Syndrome Indicate a Certain Clinical Immunological Phenotype date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16905 sentences = 873 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-022631-s4n24xij.txt txt = ./txt/cord-022631-s4n24xij.txt === reduce.pl bib === id = cord-017640-i8h48ny6 author = Fouqué, Amélie title = The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date = 2020-01-03 pages = extension = .txt mime = text/plain words = 8811 sentences = 419 flesch = 39 summary = The intrinsic pathway stems from accumulation of DNA damage, deregulation of mitochondrial function, or virus infection and induces the release of proapoptotic factors from the mitochondria, whereas extrinsic signals are transmitted by the binding of apoptotic ligands to death receptors present at the cell surface. During interactions with respective ligands, members of the death receptor superfamily recruit adaptor proteins such as Fas-associated protein with a death domain (FADD) [7, 8] or tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) [9] , resulting in the aggregation and activation of the initiators caspase-8 and caspase-10 to form the death-inducing signaling complex (DISC) [10] . These type I transmembrane proteins share common features, such as extracellular amino-terminal cysteine-rich domains (CRDs) [19, 20] , which contribute to ligand specificity [21] , and pre-association of the receptor at the plasma membrane [22] [23] [24] and a conserved 80-amino acid sequence located in their cytoplasmic tail called death domain (DD), which is necessary for DISC formation and initiation of the apoptotic signal [25, 26] . cache = ./cache/cord-017640-i8h48ny6.txt txt = ./txt/cord-017640-i8h48ny6.txt === reduce.pl bib === id = cord-023374-87ob1exq author = Sukhija, S. title = Levels, Complement Activity and Polymorphisms of Mannan‐Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16891 sentences = 869 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023374-87ob1exq.txt txt = ./txt/cord-023374-87ob1exq.txt === reduce.pl bib === id = cord-023394-ptfjxpo6 author = Isa, A. title = Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16904 sentences = 872 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023394-ptfjxpo6.txt txt = ./txt/cord-023394-ptfjxpo6.txt === reduce.pl bib === id = cord-023950-nv0pbbu2 author = Schnyder, Bruno title = Dual Role of Th17 Cytokines, IL-17A,F, and IL-22 in Allergic Asthma date = 2012-07-19 pages = extension = .txt mime = text/plain words = 4439 sentences = 245 flesch = 41 summary = Unchecked activation of Th17 cells by IL-23 is linked to chronic inflammation in experimental autoimmune encephalomyelitis (EAE) and type II collagen-induced arthritis, two heretofore prototypical "Th1" disease models [6, 7] . Furthermore, Murdoch and Lloyd provide evidence in the model of acute allergen-induced response that the gdT cell-dependent normalization of lung function and resolution of inflammation was dependent on the production of IL-17 [16] . These data provide evidence that IL-17A,F and IL-22 besides their inflammatory role have a negative regulatory function in allergic lung inflammation. On a mechanistic level, IL-17A elicits dual effects and reportedly promotes expression of proinflammatory (hemopoietic, CXC-chemokines, acute phase) factors [54, 55] , whereas it inhibits the production of mononuclear cell recruiting molecules like TNF-induced VCAM-1 and CC-chemokine RANTES [35] . IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation cache = ./cache/cord-023950-nv0pbbu2.txt txt = ./txt/cord-023950-nv0pbbu2.txt === reduce.pl bib === id = cord-023389-ilrp8vb7 author = Wefer, J. title = Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16845 sentences = 866 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023389-ilrp8vb7.txt txt = ./txt/cord-023389-ilrp8vb7.txt === reduce.pl bib === id = cord-022353-q2k2krnm author = W. Quimby, Fred title = Clinical Chemistry of the Laboratory Mouse date = 2007-09-02 pages = extension = .txt mime = text/plain words = 30195 sentences = 1702 flesch = 48 summary = Assessment of long-term average blood glucose levels in mice is also available by RIAs measuring glycosylated hemoglobin and glycosylated serum proteins (collectively known as fructosamines) (Gould et al. Leptin resistance, a common feature of obesity in mice and humans, has also been shown to result, in part, from the shedding of membrane-bound hepatic leptin receptors into the plasma, where soluble receptors modulate circulating leptin levels and possibly its biologic activity (Cohen et al. d. OTHER ANALYTES ASSOCIATED WITH LIPID METABOLISM AND ATHEROSCLEROSIS IN MICE ELISA kits are commercially available for the quantitation of many mouse coagulation proteins including: fibrinogen, factor VII, d-dimer, tissue factor, and von Willebrand's factor antigen. The ability of the first component of complement, C1, to bind specific sites on the heavy chain of mouse IgG2b and activate a sequence of reactions leading to production of a molecular unit capable of lysing a target cell membrane has established the complement system as the primary mediator of antibody-antigen reactions. cache = ./cache/cord-022353-q2k2krnm.txt txt = ./txt/cord-022353-q2k2krnm.txt === reduce.pl bib === id = cord-016960-xhzvp35g author = Berencsi, György title = Fetal and Neonatal Illnesses Caused or Influenced by Maternal Transplacental IgG and/or Therapeutic Antibodies Applied During Pregnancy date = 2012-03-08 pages = extension = .txt mime = text/plain words = 17693 sentences = 1045 flesch = 42 summary = The importance of maternal anti-idiotypic antibodies are believed to prime the fetal immune system with epitopes of etiologic agents infected the mother during her whole life before pregnancy and delivery. Neonatal lupus is a model of passively acquired autoimmunity in which a mother-, who may have systemic lupus erythematosus (SLE) or Sj€ ogren's syndrome (SS) or may be entirely asymptomatic-synthesizes antibodies to SSA/Ro and/or SSB/ La ribonucleoproteins that enter the fetal circulation via trophoblast FcRn receptors and presumably cause tissue injury (Lee 1990 ) as mentioned above. Teplizumab (CD3-specific, hOKT3g1-Ala-Ala), a humanized Fc mutated anti-CD3 monoclonal antibody induced tolerance, on the progression of type 1 diabetes in patients with recent-onset disease even 2 years after the first diagnosis (Herold et al. Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells cache = ./cache/cord-016960-xhzvp35g.txt txt = ./txt/cord-016960-xhzvp35g.txt === reduce.pl bib === === reduce.pl bib === id = cord-016523-pznw2ciu author = Fouqué, Amélie title = The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date = 2014-08-29 pages = extension = .txt mime = text/plain words = 8777 sentences = 427 flesch = 41 summary = During interactions with respective ligands, members of the death receptor superfamily recruit adaptor proteins such as Fas-associating protein with a death domain (FADD) [ 7 , 8 ] or tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) [ 9 ] , resulting in the aggregation and activation of the initiator caspase-8 and caspase-10 to form the death-inducing signaling complex (DISC) [ 10 ] . These type I transmembrane proteins share common features, such as extracellular amino-terminal cysteine-rich domains (CRDs) [ 19 , 20 ] , which contribute to ligand specifi city [ 21 ] , and preassociation of the receptor at the plasma membrane [ 22 -24 ] and a conserved 80 amino acid sequence located in their cytoplasmic tail called death domain (DD), which is necessary for DISC formation and initiation of the apoptotic signal [ 25 , 26 ] . cache = ./cache/cord-016523-pznw2ciu.txt txt = ./txt/cord-016523-pznw2ciu.txt === reduce.pl bib === id = cord-013803-d1sbfibq author = Abu El-Asrar, Ahmed M. title = Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis date = 2019-12-05 pages = extension = .txt mime = text/plain words = 4665 sentences = 262 flesch = 42 summary = title: Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis Previous studies demonstrated upregulation of proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, IL-15 and IL-17 in the aqueous humour (AH) samples from autoimmune uveitis patients [1] [2] [3] [4] [5] . For these reasons, we analyzed the AH from patients with active uveitis associated with four systemic inflammatory diseases (sarcoidosis, VKH disease, BD and HLA-B27-related inflammation) for the presence of sCD30, sCD163, sgp130, sIL-6R, sTNFRI and sTNFRII. Compared with controls, TNF-α, sCD163, sgp130, sIL-6R, sTNFRI and sTNFRII levels were significantly higher in BD and HLA-B-27-associated uveitis. Among the cytokine and soluble cytokine receptors analyzed, TNF-α and sCD30 differed significantly between patients with BD, sarcoidosis, HLA-B27-associated uveitis and VKH disease (p = 0.029; p = 0.001, respectively) (Fig. 1a) . cache = ./cache/cord-013803-d1sbfibq.txt txt = ./txt/cord-013803-d1sbfibq.txt === reduce.pl bib === id = cord-023433-d1b7qvhs author = Siassi, M. title = Expression of Human Collectins in Colorectal Carcinoma date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16906 sentences = 879 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023433-d1b7qvhs.txt txt = ./txt/cord-023433-d1b7qvhs.txt === reduce.pl bib === id = cord-023410-eblcf902 author = Kollgaard, T. M. title = Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16915 sentences = 872 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023410-eblcf902.txt txt = ./txt/cord-023410-eblcf902.txt === reduce.pl bib === id = cord-017309-pt27efu1 author = Gupta, G. S. title = Selectins and Associated Adhesion Proteins in Inflammatory disorders date = 2012-03-20 pages = extension = .txt mime = text/plain words = 25423 sentences = 1303 flesch = 40 summary = Activation of endothelial cells (EC) with different stimuli induces the expression of E-and P-selectins, and other adhesion molecules (ICAM-1, VCAM-1), involved in their interaction with circulating cells. Accordingly, population studies have explored the association of ischaemic heart disease with gene polymorphisms of the inflammatory molecules: tumor necrosis factors (TNF) a and b, transforming growth factors (TGF) b1 and 2, P and E selectins, and platelet endothelial cell adhesion molecule (PECAM) 1. Endothelial dysfunction in type 2 diabetic patients is associated with inflammation, increased levels of circulating soluble adhesion molecules (VCAM-1 and E-selectin), and inducing production of ROS, and urinary albumin excretion (Potenza et al. The A 561 C polymorphism of E-selectin gene may be associated with disease progression in patients with chronic HBV infection and control the expression of plasma soluble levels, while the G 98 T polymorphism may be related to fibrotic severity in Chinese population (Wu et al. cache = ./cache/cord-017309-pt27efu1.txt txt = ./txt/cord-017309-pt27efu1.txt === reduce.pl bib === id = cord-262511-96xp1v0r author = Khabar, Khalid S. A. title = Rapid transit in the immune cells: the role of mRNA turnover regulation date = 2007-03-30 pages = extension = .txt mime = text/plain words = 6542 sentences = 342 flesch = 43 summary = Post-transcriptional regulation contributes significantly to this rapid transit by several mechanisms, including mRNA stability modulation and translational control; collectively, they aim to control the expression of key gene products involved in the immune response. The stabilization of cytokine mRNA and other immune response gene products can occur by the activity of mRNA stabilization-promoting proteins such as human antigen (HuR) protein or by inactivation of RNA decay-promoting proteins such as the zinc finger protein, tristetraprolin (TTP). Traditionally, post-transcriptional regulation in innate immunity has been studied in response to the bacterial endotoxin, LPS, which binds CD14 in a complex with TLR4 on the surface of neutrophils and macrophages and initiates a cascade of signals that causes cell activation, the inflammatory response, and phagocytosis [35] . With the coordinated kinetics model, stabilizing RNA-binding proteins such as HuR can occur initially following immune cell activation, allowing rapid and early response of cytokine production. cache = ./cache/cord-262511-96xp1v0r.txt txt = ./txt/cord-262511-96xp1v0r.txt === reduce.pl bib === id = cord-023407-s85g7g0x author = Huang, Y.‐M. title = Anti‐Inflammatory Liver X Receptors and Related Molecules in Multiple Sclerosis Patients from Sardinia and Sweden date = 2008-06-28 pages = extension = .txt mime = text/plain words = 17075 sentences = 876 flesch = 47 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023407-s85g7g0x.txt txt = ./txt/cord-023407-s85g7g0x.txt === reduce.pl bib === id = cord-272237-gnno6elo author = Wang, Ziran title = A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids date = 2020-07-31 pages = extension = .txt mime = text/plain words = 4472 sentences = 241 flesch = 53 summary = A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). cache = ./cache/cord-272237-gnno6elo.txt txt = ./txt/cord-272237-gnno6elo.txt === reduce.pl bib === id = cord-023414-xxw5kptr author = Chistensen, H. R. title = Characterization of a Large Panel of Lactic Acid Bacteria Derived from the Human Gut for their Capacity to Polarize Dendritic Cell date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16914 sentences = 872 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023414-xxw5kptr.txt txt = ./txt/cord-023414-xxw5kptr.txt === reduce.pl bib === id = cord-023387-tyeh14wz author = Hvas, C. L. title = Probiotic Bacteria Induce Regulatory Cytokine Production via Dendritic Cells date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16893 sentences = 881 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023387-tyeh14wz.txt txt = ./txt/cord-023387-tyeh14wz.txt === reduce.pl bib === id = cord-276564-o21ncldx author = Miller, R. title = COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity date = 2020-06-29 pages = extension = .txt mime = text/plain words = 3229 sentences = 205 flesch = 44 summary = This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. Vulnerable patient groups would potentially be less likely or unable to ensure sufficient activation of SIRT1 due to low NAD + levels or associated nutritional deficiencies including Zn ++ , and as such contribute to an inability to control viral replication and reduce the uncontrolled expression of pro-inflammatory cytokines. cache = ./cache/cord-276564-o21ncldx.txt txt = ./txt/cord-276564-o21ncldx.txt === reduce.pl bib === id = cord-023935-o2ffxgnn author = Lorts, Angela title = Sepsis date = 2011-12-16 pages = extension = .txt mime = text/plain words = 11110 sentences = 510 flesch = 38 summary = SIRS i s a state of infl ammatory/ immune activation and is based on the presence of at least two of the four following clinical criteria: Temperature >38°C or <36°C, heart rate >90th percentile for age, respiratory rate >90th percentile for age, or hyperventilation to PaCO 2 < 32 mm Hg. The defi nition attempts to "capture" all patients at risk for the subsequent development of severe sepsis or septic shock. Among these, the nuclear factor-k B (NF-k b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. Nuclear factork B (NFk b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. cache = ./cache/cord-023935-o2ffxgnn.txt txt = ./txt/cord-023935-o2ffxgnn.txt === reduce.pl bib === id = cord-023430-5zuewjv2 author = Nilkaeo, A. title = Interleukin‐18 Inhibition of Oral Carcinoma Cell Proliferation date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16908 sentences = 866 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023430-5zuewjv2.txt txt = ./txt/cord-023430-5zuewjv2.txt === reduce.pl bib === === reduce.pl bib === id = cord-020757-q4ivezyq author = Saikumar, Pothana title = Apoptosis and Cell Death: Relevance to Lung date = 2010-05-21 pages = extension = .txt mime = text/plain words = 7402 sentences = 420 flesch = 39 summary = The extrinsic pathway involves binding of death ligands such as tumor necrosis factor-α (TNF-α), CD95 ligand (Fas ligand), and TNF-related apoptosis-inducing ligand (TRAIL) to their cognate cell surface receptors TNFR1, CD95/Fas, TRAIL-R1, TRAIL-R2, and the DR series of receptors, 29 resulting in the activation of initiator caspase-8 (also known as FADD-homologous ICE/CED-3-like protease or FLICE) and subsequent activation of effector caspase-3 ( Figure 4 .2). In cytotoxic T lymphocyte-induced death, granzyme B, which enters the cell through membrane channels formed by the protein perforin, activates caspases by cleaving them directly or indirectly. Intracellular Pathways: Lack of survival stimuli (withdrawal of growth factor, hypoxia, genotoxic substances, etc.) is thought to generate apoptotic signals through ill-defi ned mechanisms, which lead to translocation of proapoptotic proteins such as Bax to the outer mitochondrial membrane. For example, agents that damage DNA, such as ionizing radiation and certain xenobiotics, lead to activation of p53-mediated mechanisms that commit cells to apoptosis, at least in part through transcriptional upregulation of proapoptotic proteins. cache = ./cache/cord-020757-q4ivezyq.txt txt = ./txt/cord-020757-q4ivezyq.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-023388-btbf6wkg author = Hoffmann, H. J. title = Decrease in Fine T‐cell Subset ratio MT2/MT1 During Steroid Reduction of Asthmatic Patients date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16918 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023388-btbf6wkg.txt txt = ./txt/cord-023388-btbf6wkg.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-269986-jdcw59r2 author = Regan, Andrew D. title = Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells date = 2009-02-05 pages = extension = .txt mime = text/plain words = 5516 sentences = 260 flesch = 50 summary = Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors. To determine whether viral replication was required for FIPV-induced p38 MAPK activation, UV-inactivated virus was added to PFBM cells and analyzed by western blot as described above (Fig. 1B) . Overall these data indicate that production of the pro-inflammatory cytokine TNF-alpha in FIPVinfected PFBM cells is regulated by activation of the p38 MAPK pathway. In this study we show that infection by FIPV causes a rapid activation the p38 MAPK pathway in PFBM cells, and that this process directly regulates production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta. cache = ./cache/cord-269986-jdcw59r2.txt txt = ./txt/cord-269986-jdcw59r2.txt === reduce.pl bib === id = cord-023391-bq5w3jk9 author = Utermöhlen, O. title = Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16856 sentences = 870 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023391-bq5w3jk9.txt txt = ./txt/cord-023391-bq5w3jk9.txt === reduce.pl bib === === reduce.pl bib === id = cord-023429-x52gbklw author = Ruseva, M. title = Mannan‐Binding Lectin Inhibits Humoural Responses date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16880 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023429-x52gbklw.txt txt = ./txt/cord-023429-x52gbklw.txt === reduce.pl bib === id = cord-256837-100ir651 author = Smith, Steven B. title = Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date = 2012-03-14 pages = extension = .txt mime = text/plain words = 8447 sentences = 415 flesch = 38 summary = Several recent studies have generated multiple mRNA microarray gene expression datasets derived from experiments involving the infection of human cell-lines or animal models with one or more of the major respiratory viruses [21] [22] [23] . Through a systematic analysis of these respiratory virus-human host gene expression datasets, we determined common sets of genes and pathways involved in host responses to viral infections. A total of seven different respiratory viruses were analyzed, represented by fifteen unique Gene Expression Omnibus (GEO) datasets (indicated by GEO Series or GSE accession numbers), nine different human cell types, and seven different array platforms for a total of 28 unique comparisons. This assumption is based on the occurrence of genes that are differentially expressed in infection models for at least five of the seven respiratory viruses, have involvement in a number of relevant pathways related to host immune response, and encode for known drug targets. cache = ./cache/cord-256837-100ir651.txt txt = ./txt/cord-256837-100ir651.txt === reduce.pl bib === id = cord-023415-hhvmsn5b author = Karlsson, H. title = Pattern of Cytokine Responses to Gram‐Positive and Gram‐Negative Commensal Bacteria is Profoundly Changed when Monocytes Differentiate into Dendritic Cells date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16909 sentences = 868 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023415-hhvmsn5b.txt txt = ./txt/cord-023415-hhvmsn5b.txt === reduce.pl bib === id = cord-023438-g0k0vvdc author = Krog, J. title = The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells, with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16880 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023438-g0k0vvdc.txt txt = ./txt/cord-023438-g0k0vvdc.txt === reduce.pl bib === id = cord-267270-r17z4d8x author = Kipar, A. title = Age-related dynamics of constitutive cytokine transcription levels of feline monocytes date = 2005-01-18 pages = extension = .txt mime = text/plain words = 2695 sentences = 141 flesch = 53 summary = However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15 mo to 10 yr) were examined for transcription of IL-1β, IL-6, IL-10, IL-12 p40 and TNF-α by real-time PCR. One previous study actually showed significantly increased constitutive production of IL-1b and IL-6 in circulating monocytes of older female compared to young adult female human individuals, whereas no changes in the constitutive TNF-a production were observed (Sadeghi et al., 1999) . It seems plausible that despite increased or similar constitutive cytokine transcription, monocytes of older cats might exhibit an impaired reactive activation after virus infection (Kipar et al., 2005) . cache = ./cache/cord-267270-r17z4d8x.txt txt = ./txt/cord-267270-r17z4d8x.txt === reduce.pl bib === id = cord-275730-650sjwyy author = Gogoi, Himanshu title = The Age of Cyclic Dinucleotide Vaccine Adjuvants date = 2020-08-13 pages = extension = .txt mime = text/plain words = 8347 sentences = 519 flesch = 50 summary = As therapeutic cancer vaccine adjuvants, CDNs induce potent anti-tumor immunity, including cytotoxic T cells and NK cells activation that achieve durable regression in multiple mouse models of tumors. (STINGel) Synthetic ML-RpRp-SS-CDA in multidomain peptide hydrogel (s.c.) [60] Slow-release of CDN and highly effective in maintaining tumor clearance and rejecting tumor growth and provide durable anti-tumor immunity CDG in YSK05 liposome (s.c.) [61] Activation of antigen-specific CTL activity and restrict murine tumor growth completely ADU-S100 (Synthetic ML-RpRp-SS-CDA) in combination with anti-PD1 or anti-CTLA4 antibody (intratumoral) [62] Low-dosage promotes local STING activation primarily in monocytic cell lineages whereas a high-dose resulted in cellular activation at distal sites A combination of ADU-S100 and α-CPI provide durable immunity even against cold tumors Synthetic RpRp-SS-CDG and ML-RpRp-CDA in PBAE nanoparticles and anti-PD1 antibody (intratumoral) [56] Enhanced shelf-life stability for up to nine months. cache = ./cache/cord-275730-650sjwyy.txt txt = ./txt/cord-275730-650sjwyy.txt === reduce.pl bib === id = cord-275413-e2rhioty author = Rowland, Raymond R.R. title = The interaction between PRRSV and the late gestation pig fetus date = 2010-09-09 pages = extension = .txt mime = text/plain words = 6183 sentences = 344 flesch = 50 summary = The purpose of this study was to characterize the interaction between PRRSV and the pig fetus by (1) identifying sites of virus replication, (2) measuring immune and inflammatory cytokines in different compartments, and (3) evaluating the response of lymph nodes. Maternal, accessory and fetal tissues were collected and stored in formalin for histological staining and immunohistochemistry (IHC), or storage in RNAlater (Ambion) for RT-PCR of cytokine mRNAs. PRRSV-specific antibody was measured in sera using the HerdCheck ® PRRS ELISA (IDEXX) and performed by personnel at Kansas State University Veterinary Diagnostic Laboratory. As shown in Fig. 4A , IFN-␥ and TNF-␣ PCR products were not detected in lung, lymph node or placenta from the non-infected fetuses. To determine if cytokine gene expression was the direct result of PRRSV infection, RT-PCR for IFN-␥ and TNF-␣ was performed on the same tissues from fetuses of infected dam no. cache = ./cache/cord-275413-e2rhioty.txt txt = ./txt/cord-275413-e2rhioty.txt === reduce.pl bib === id = cord-272695-wmzq4lkh author = Ahmed, Ahmed A. title = TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis date = 2020-05-13 pages = extension = .txt mime = text/plain words = 3813 sentences = 210 flesch = 55 summary = This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. The amplified PCR product for TNF-α-308 was detected at 184 base pair as shown in Fig. 1 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls (supplementary file (Table 3 ). The amplified PCR product for IFN-γ + 874 were detected at 263 base pair as shown in Fig. 2 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls. cache = ./cache/cord-272695-wmzq4lkh.txt txt = ./txt/cord-272695-wmzq4lkh.txt === reduce.pl bib === id = cord-023443-pvz7dll9 author = nan title = Abstracts for the Scandinavian Society for Immunology 35th Annual Meeting and 20th Summer School date = 2004-06-02 pages = extension = .txt mime = text/plain words = 16643 sentences = 857 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023443-pvz7dll9.txt txt = ./txt/cord-023443-pvz7dll9.txt === reduce.pl bib === id = cord-256838-8rzibpbl author = Eng, Yi Shin title = Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples date = 2019-09-27 pages = extension = .txt mime = text/plain words = 9233 sentences = 505 flesch = 39 summary = There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Several factors may affect the molecular mechanisms and subsequent clinical effects of TCM formulas, including individual gene-based response, composition and amount of active molecules in TCM formulas, complex interactions, and appropriateness of use of TCM formulas. From the viewpoint of pathophysiology, TCM formulas used to manage airway viral infections need to have antiviral activity against such viruses listed above, and/or to induce antiviral cytokines, and/or anti-inflammatory effect, and/or to relieve symptoms commonly presented in airway infections ( Figure 1 ). To simplify the molecular mechanisms and to correlate the pharmacologic activities with their clinical effects, five formulas of A-physicians will be used as examples against airway infections: Several health benefits of herbal medicine and TCM are claimed; for example, herbs and TCM formulas, including those discussed above, are believed to have anti-oxidative activities helpful against several diseases. cache = ./cache/cord-256838-8rzibpbl.txt txt = ./txt/cord-256838-8rzibpbl.txt === reduce.pl bib === id = cord-023445-c4tqioz1 author = Lauridsen, C. title = Supplementation of Vitamin C to Weaner Diets Increases IgM Concentration and Improves the Biological Activity of Vitamin E in Alveolar Macrophages date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16947 sentences = 870 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023445-c4tqioz1.txt txt = ./txt/cord-023445-c4tqioz1.txt === reduce.pl bib === id = cord-270414-gh9agf4x author = Fischer, Y. title = Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis date = 2011-10-12 pages = extension = .txt mime = text/plain words = 4579 sentences = 278 flesch = 54 summary = title: Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis Several case reports can be found in the online Veterinary Information Network (http://www.VIN.com) that describe a positive effect of the methylxanthine derivative pentoxifylline (PTX) (Trental a ) on the survival time in cats with FIP. ALT alanine aminotransferase AP alkaline phosphatase CI confidence interval FCoV feline coronavirus FeLV feline leukemia virus FIP feline infectious peritonitis FIPV feline infectious peritonitis virus FIV feline immundeficiency virus IFAT immunofluorescent antibody technique PPF propentofylline PTX pentoxifylline RBC red blood cells SPSS statistical package for the social sciences TNF-a tumor necrosis factor-alpha TP total protein WBC white blood cells which cause endothelial cell damage. The aim of this study was to evaluate the efficacy of PPF on the survival time and quality of life in cats with a confirmed diagnosis of FIP in a placebocontrolled double-blind trial. cache = ./cache/cord-270414-gh9agf4x.txt txt = ./txt/cord-270414-gh9agf4x.txt === reduce.pl bib === id = cord-023439-r04y1j22 author = Hedegaard, C. J. title = The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4(+) T‐cell Responses to MBP in Health and Multiple Sclerosis date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16932 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. cache = ./cache/cord-023439-r04y1j22.txt txt = ./txt/cord-023439-r04y1j22.txt === reduce.pl bib === id = cord-252725-e3pazjdi author = Khalil, Ayman title = The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal date = 2020-10-15 pages = extension = .txt mime = text/plain words = 8759 sentences = 338 flesch = 30 summary = In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID-19 through the enhancement of host immune response against viral infections by different biological mechanisms. Actually, data indicated that activation of the nuclear factor (NF)-κB transcription factor (NF-κB) signaling pathway represents a major contribution to the inflammation induced post SARS-CoV infection and that NF-κB inhibitors are promising antiviral drugs against infections caused by the virus and potentially other pathogenic human coronaviruses [8] . Moreover, it was found to reduce the reactive oxygenated species (ROS) produced during viral infection and subsequently decrease pro-inflammatory markers such as IL-8, TNF-α, IL-1β and IL-6 [25] and increases anti-inflammatory cytokines such as IL-10 [35] , indicating that it has clear antiviral effects on several respiratory and common cold viruses through its ability to reduce virus imputation, replication and viral load in vitro, as well as lung inflammation and airways hyper-responsiveness in vivo [29] . cache = ./cache/cord-252725-e3pazjdi.txt txt = ./txt/cord-252725-e3pazjdi.txt === reduce.pl bib === id = cord-295683-eoxxal8v author = Gong, R. title = Hepatocyte growth factor suppresses acute renal inflammation by inhibition of endothelial E-selectin date = 2006-04-01 pages = extension = .txt mime = text/plain words = 4481 sentences = 266 flesch = 42 summary = This study examined the effect of HGF on endothelial E-selectin expression in acute inflammation induced by tumor necrosis factor (TNF)-α. In vitro, HGF suppressed TNF-α-induced cell surface expression of E-selectin in human umbilical vein endothelial cells (HUVEC) and inhibited E-selectin mediated monocytic adhesion to endothelial monolayers. In addition, selective inhibition of GSK3 activity by lithium suppressed TNF-α-induced E-selectin expression and monocytic adhesion, reminiscent of the action of HGF. [6] [7] [8] [9] [10] In the present study, we found that HGF suppresses monocyte to endothelial adhesion and attenuates acute renal inflammation via inhibition of endothelial E-selectin expression. In our study, HGF was found to suppress endothelial E-selectin expression in cultured HUVEC cells and in vivo in rats injected with TNF-a. In summary, HGF suppresses E-selectin expression in the activated endothelium and thereby attenuates monocyte to endothelial adhesion and alleviates acute inflammation in the kidney. cache = ./cache/cord-295683-eoxxal8v.txt txt = ./txt/cord-295683-eoxxal8v.txt === reduce.pl bib === id = cord-271114-hv3gwvdi author = Allam, Gamal title = Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms date = 2015-04-22 pages = extension = .txt mime = text/plain words = 5564 sentences = 313 flesch = 52 summary = The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. Therefore, the primary aim of the current study was to investigate SNPs in the IL-1β -31 T/C (rs1143643), IL-6 -174 G/C (rs1800795), TNF-α -308 G/A (rs1800629), and IFN-γ +874 A/T (rs2430561) genes for their possible association with susceptibility to EOS in Saudi newborn infants. Newborns with sepsis had significantly higher serum levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) compared to both suspected and sepsis-free control groups (overall p value < 0.001, Table 1 ). cache = ./cache/cord-271114-hv3gwvdi.txt txt = ./txt/cord-271114-hv3gwvdi.txt === reduce.pl bib === id = cord-023928-9a1w174h author = Thomas, Neal J. title = Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date = 2011-12-16 pages = extension = .txt mime = text/plain words = 12255 sentences = 510 flesch = 46 summary = authors: Thomas, Neal J.; Dahmer, Mary K.; Quasney, Michael W. Examples of the infl uence of genetic variations in proteins involved in recognition of pathogens on the severity of infections include polymorphisms in the genes coding for mannose binding Individual variability in the susceptibility to and outcome from critical care diseases has long been observed, and advances in genomic medicine now gives an opportunity to understand these differences. cache = ./cache/cord-023928-9a1w174h.txt txt = ./txt/cord-023928-9a1w174h.txt === reduce.pl bib === id = cord-295523-5pv7kw6i author = Picchianti Diamanti, Andrea title = Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity date = 2020-05-08 pages = extension = .txt mime = text/plain words = 7905 sentences = 390 flesch = 39 summary = However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). We critically review the rationale for the adoption of immunosuppressive agents, commonly used in autoimmune diseases, in the treatment of SARS-CoV-2 infection and report current knowledge of ongoing studies. The exacerbated reaction to infections or to biological therapy is caused by the rapid recruitment of macrophages and neutrophils, which produce pro-inflammatory cytokines and alter the fragile balance between a controlled immune response and a host-damaging reaction. As of now, four clinical trials are recruiting patients with COVID-19, severe acute respiratory failure, and CRS, aiming at evaluating the safety and effectiveness of anakinra alone or in combination with anti-IL-6 agents (NCT04330638, NCT0432402, NCT04357366, NCT04339712). High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis cache = ./cache/cord-295523-5pv7kw6i.txt txt = ./txt/cord-295523-5pv7kw6i.txt === reduce.pl bib === id = cord-271812-ldwb05xn author = Prasad, Ananda S. title = Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease(1)(2)(3) date = 2013-03-01 pages = extension = .txt mime = text/plain words = 12220 sentences = 617 flesch = 49 summary = Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson's disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. AE is a lethal, autosomal, recessive trait that usually occurs in infants of Italian, Armenian, or Iranian lineage 4 Abbreviations used: AB, b amyloid protein; AD, Alzheimer's disease; AE, acrodermatitis enteropathica; APP, amyloid precursor protein; CRP, C-reactive protein; DC, dendritic cells; HAE, 4-hydroxyalkenal; HAEC, human vascular endothelial cell; HL-60, human promyelocytic leukemia cell line; ICAM-1, intercellular adhesion molecule 1; IFN, interferon; IGF-1, insulin-like growth factor 1; MDA, malondialdehyde; MNC, mononuclear cell; NF-kB, nuclear factor kB; oxLDL, oxidized LDL; PHA-P, phytohemagglutinin P; PMA, phorbol-12 myristate 13 acetate; ra, receptor antagonist; RDA, recommended daily allowance; ROS, reactive oxygen species; SCD, sickle cell disease; sIL-1 ra, soluble interleukin-1 receptor antagonist; THP-1, human monocytic leukemia cell line; TK, deoxythymidine kinase; VCAM-1, vascular cell adhesion molecule 1. cache = ./cache/cord-271812-ldwb05xn.txt txt = ./txt/cord-271812-ldwb05xn.txt === reduce.pl bib === id = cord-278339-6ddsj014 author = Gianfrancesco, Milena title = Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry date = 2020-05-29 pages = extension = .txt mime = text/plain words = 5376 sentences = 298 flesch = 41 summary = The independent associations between demographic and disease-specific features with the odds of COVID-19 hospitalisation were estimated using multivariable-adjusted logistic regression and reported as OR and 95% CIs; covariates included in the model were age group (<65 years vs >65 years), sex, rheumatic disease (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) or other spondyloarthritis, vasculitis and other), key comorbidities (hypertension, lung disease, diabetes, cardiovascular disease and chronic renal insufficiency/end-stage renal disease), smoking status (ever vs never), physician-reported disease activity (remission, minimal/low disease activity, moderate disease activity or severe/high disease activity; or as a binary variable: remission and minimal/low disease activity vs moderate and severe/high disease activity), DMARD type (no DMARD, csDMARD only, b/tsDMARD only, csDMARD and b/tsDMARD combination therapy), non-steroidal anti-inflammatory drugs (NSAID) use (yes vs no) and prednisone-equivalent glucocorticoid use (0 mg/ day, 1-9 mg/day, ≥10 mg/day). cache = ./cache/cord-278339-6ddsj014.txt txt = ./txt/cord-278339-6ddsj014.txt === reduce.pl bib === id = cord-259586-kep2dgaw author = Van Reeth, Kristien title = In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding date = 2002-09-10 pages = extension = .txt mime = text/plain words = 4193 sentences = 231 flesch = 49 summary = This review concentrates on in vivo studies of cytokine involvement in infectious respiratory diseases of swine, with an emphasis on viral infections. In the authors' laboratory, studies were undertaken to investigate the relationship between viral respiratory disease and bioactive lung lavage levels of IFN-α, TNF-α, IL-1 and IL-6. We have previously demonstrated different cytokine pro-®les in BAL¯uids of gnotobiotic pigs infected with porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) or swine in¯uenza virus (SIV) (Van Reeth et al., 1999) . In an attempt to study interactions between respiratory viruses and secondary agents in a reproducible way, we have performed subsequent inoculations of pigs with either PRCV or PRRSV followed by bacterial lipopolysaccharide (LPS). Prior infection with PRCV truly potentiated the cytokine response to LPS, with 10±100 times higher titres of TNF-a, IL-1 and IL-6 than after the respective single inoculations. Differential production of proin¯ammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity cache = ./cache/cord-259586-kep2dgaw.txt txt = ./txt/cord-259586-kep2dgaw.txt === reduce.pl bib === id = cord-280599-7ixpqd5n author = OPENSHAW, P J M title = What does the peripheral blood tell you in SARS? date = 2004-04-01 pages = extension = .txt mime = text/plain words = 1227 sentences = 64 flesch = 51 summary = However, cytokine release is often very local, as illustrated by studies of TNF production in patients with bacterial pneumonia that show TNF levels to be high in bronchial lavage fluid from the affected lung, but not in fluid from the contralateral lung or in serum [4] . More importantly, anti-TNF therapy works well in many patients with rheumatoid arthritis or juvenile RA, but measurement of cytokines in serum and synovial fluid does not show raised levels of TNF [9] . So, what can we expect to learn by profiling cytokine production or levels in blood samples from patients with inflammatory diseases? Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls cache = ./cache/cord-280599-7ixpqd5n.txt txt = ./txt/cord-280599-7ixpqd5n.txt === reduce.pl bib === id = cord-259367-2e998to9 author = Jacques, Alexandre title = Macrophage interleukin-6 and tumour necrosis factor-α are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a date = 2009-09-01 pages = extension = .txt mime = text/plain words = 6412 sentences = 370 flesch = 51 summary = In this study, we demonstrate that the pro-inflammatory cytokines IL-6 and TNF-a, produced by MHV3-infected peritoneal macrophages, were induced by the fixation of protein S of MHV3 on TLR2 associated with regions enriched in heparan sulphate instead of CEA-CAM1a. 23, 44 To determine whether that the pro-inflammatory cytokines induced by L2-MHV3 in macrophages depend on viral fixation to regions enriched in heparan sulphate, resident peritoneal macrophages from C57BL/6 and Ceacam1a )/) mice were treated in vitro with heparin and infected further with L2-MHV3. To identify the intracellular signalling pathways involved in the TLR2/heparan sulphate region-dependent production of IL-6 and TNF-a, peritoneal macrophages from C57BL/6 and Ceacam1a )/) mice were treated with p38 (SB203580) and ERK-1/2 (U0126) MAPK inhibitors and infected in vitro with L2-MHV3. 21, 48, 49 However, we have demonstrated that viral fixation to the CEACAM1a receptor is not directly involved in the secretion of IL-6 and TNF-a by MHV3-infected peritoneal macrophages as these cytokines were also induced in cells from Ceacam1a )/) mice and regulated by the MAPK pathways. cache = ./cache/cord-259367-2e998to9.txt txt = ./txt/cord-259367-2e998to9.txt === reduce.pl bib === id = cord-308008-s2t11l3h author = Limonta, Daniel title = Apoptotic mediators in patients with severe and non‐severe dengue from Brazil date = 2013-10-29 pages = extension = .txt mime = text/plain words = 6077 sentences = 320 flesch = 49 summary = Therefore, plasma levels of the three proapoptotic mediators Fas ligand (FasL), tumor necrosis factor-a (TNF-a), and TNF-related apoptosis-inducing ligand (TRAIL) were measured in dengue patients. Previous studies of dengue infection have shown apoptosis in lymphocytes [Mongkolsapaya et al., 2003; Myint et al., 2006] , monocytes [Torrentes-Carvalho et al., 2009; Levy et al., 2010] , and peripheral blood mononuclear cells (PBMCs) [Jaiyen et al., 2009] . The other proteins studied, plasma Survivin and PBMCs lysate proteins, are IAPs. Our data suggest that TRAIL could be involved with apoptosis induction of blood lymphocytes and could also contribute to the antiviral response. In the present study, elevated TRAIL levels were observed in patients with dengue without warning signs compared to those with severe dengue and control subjects. The findings in the present work, which used the revised WHO dengue classification, suggest that the antiviral action of TRAIL that was shown previously in cell culture [Warke et al., 2008b] , may also occur in vivo and hence the likely increased severity of dengue in patients lacking an elevated TRAIL production. cache = ./cache/cord-308008-s2t11l3h.txt txt = ./txt/cord-308008-s2t11l3h.txt === reduce.pl bib === id = cord-301946-erzh30mt author = Kwak-Kim, Joanne title = COVID-19 and immunomodulation treatment for women with reproductive failures date = 2020-06-12 pages = extension = .txt mime = text/plain words = 5604 sentences = 335 flesch = 42 summary = With the Coronavirus Disease 2019 (COVID-19) pandemic, patient care has been significantly challenged not only for the COVID-19 cases but for the others, including pregnant women with a history of reproductive failures (RF), such as recurrent pregnancy losses (RPL), repeated implantation failures (RIF), with immune etiologies including autoimmune diseases, cellular immune dysfunction, and rheumatic conditions. SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus), which caused the SARS outbreak in 2003, infects macrophages and T cells (Perlman and Dandekar 2005) and induces various cytokines, such as type I IFN, TNF-α, IL-1, etc., and B cell-related antibodies (Prompetchara et al. With the currently available data, it is unlikely that the use of IVIg in patients with RFI will impact the chances of contracting the disease or negatively affect the clinical course in women with COVID-19 infection during pregnancy. cache = ./cache/cord-301946-erzh30mt.txt txt = ./txt/cord-301946-erzh30mt.txt === reduce.pl bib === id = cord-300991-ipy24zxp author = Khan, Amira Sayed title = Obesity and COVID-19: Oro-Naso-Sensory Perception date = 2020-07-08 pages = extension = .txt mime = text/plain words = 5971 sentences = 314 flesch = 47 summary = Through a recent upsurge of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, the clinical assessment of most of the coronavirus disease 19 (COVID-19) patients clearly presents a health condition with the loss of oro-naso-sensory (ONS) perception, responsible for the detection of flavor and savor. Hence, obesity represents a great risk factor for SARS-CoV-2 infection, as it may hide the viral-associated altered ONS symptoms, thus leading to a high mortality rate in these subjects. Moreover, the number of immunosuppressive T-regulatory, Treg (CD4 + CD25 + Foxp3 + ) cells and concentrations of IL-6, IL-10, and C-reactive protein (CRP) were upregulated in patients with severe COVID-19 [18] , suggesting that SARS-CoV-2 infection may lead to "over-immunosuppression" in the case of obesity ( Figure 1 ). SARS-CoV-2 infection may further aggravate the ONS functions; mask the obesity-induced inflammation, including loss of taste and smell; and render the obese subjects more vulnerable and prone to severe pathophysiological consequences such as RTI, leading to death. cache = ./cache/cord-300991-ipy24zxp.txt txt = ./txt/cord-300991-ipy24zxp.txt === reduce.pl bib === id = cord-291076-p350i54m author = Wang, Renxi title = The role of C5a in acute lung injury induced by highly pathogenic viral infections date = 2015-05-06 pages = extension = .txt mime = text/plain words = 5790 sentences = 373 flesch = 42 summary = Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. [1] [2] [3] In addition, the complement system has been implicated in the development of acute lung diseases induced by highly pathogenic viruses including influenza A virus H1N1, 4 H5N1, 5 H7N9, 6 severe acute respiratory syndrome coronavirus (SARS-Cov), 7 Middle East respiratory syndrome coronavirus (MERS-Cov). C5a-mediated release of reactive oxygen species C5a is a strong chemoattractant for neutrophils and monocytes; it then activates these cells to generate oxidative burst with release of 10 A study demonstrated that ROS are primary pathogenic molecules in pneumonia from mice infected with influenza virus. Inhibition of Complement Activation Alleviates Acute Lung Injury Induced by Highly Pathogenic Avian Influenza H5N1 Virus Infection cache = ./cache/cord-291076-p350i54m.txt txt = ./txt/cord-291076-p350i54m.txt === reduce.pl bib === id = cord-279498-ez3yq7xi author = Suzumura, Akio title = Immune Response in the Brain: Glial Response and Cytokine Production date = 2008-12-31 pages = extension = .txt mime = text/plain words = 5319 sentences = 308 flesch = 45 summary = Cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-3 induce class I major histocompatibility complex (MHC) antigen expression on neural cells. In the brains of experimental allergic encephalomyelitis (EAE), microglia near the infiltrating T cells are reported to be class II MHC antigen-positive [6] [7] [8] , suggesting that a T cell-derived cytokine, most probably IFN-g, can induce class II MHC antigen expression in vivo as well. Since the BBB is not damaged in this experimental condition and since there is no definitive evidence that neural cells produce INF-g in the CNS, it is unlikely that IFN-g is responsible for the induction of class II MHC antigen expression in this model. In contrast to IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) downregulates IFN-g-induced class II MHC antigen expression in microglia. IL-10 suppresses cytokine production and IFN-g-induced class II MHC antigen expression in microglia, but does not suppress the proliferation or the activation of lysosomal enzymes in microglia [18] . cache = ./cache/cord-279498-ez3yq7xi.txt txt = ./txt/cord-279498-ez3yq7xi.txt === reduce.pl bib === id = cord-297128-s5c9h4lm author = Hong, Joung-Woo title = Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models date = 2012-11-28 pages = extension = .txt mime = text/plain words = 3856 sentences = 210 flesch = 52 summary = title: Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. Inhibitory effect of the CWE fraction containing highmolecular-weight compounds on signaling molecules in LPS-stimulated macrophages In addition, LPS-induced IκBα degradation and MAP kinase phosphorylation in macrophages was strongly inhibited by the polyphenol-rich CWE fraction. Oral administration of CWE decreased serum levels of LPS-induced TNF-α and IL-6, but such anti-inflammatory activity was attenuated in the high dose group. The inhibitory effect of CWE on the signaling pathways mediated by NF-κB and MAP kinases occurred in its polyphenol-rich high MW fraction. CWE inhibited IκBα degradation and MAP kinase activation in LPS-stimulated macrophages in vitro. Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models cache = ./cache/cord-297128-s5c9h4lm.txt txt = ./txt/cord-297128-s5c9h4lm.txt === reduce.pl bib === id = cord-297857-ybqj8z1r author = Petagna, L. title = Pathophysiology of Crohn’s disease inflammation and recurrence date = 2020-11-07 pages = extension = .txt mime = text/plain words = 6669 sentences = 307 flesch = 37 summary = Crohn's disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. The pathogenesis is also sustained by the interaction of these cells with integrins, adhesion molecules and multiple chemokines, responsible for the production of elevated levels of inflammatory cytokines, representing the target of immune and non-immune cells and the promotion of mucosal inflammation. A new Antimesenteric functional end-to-end Handsewn anastomosis: surgical prevention of anastomotic recurrence in Crohn's disease Surgical recurrence at anastomotic site after bowel resection in Crohn's disease: comparison of Kono-S and end-to-end anastomosis Surgical prevention of anastomotic recurrence by excluding mesentery in Crohn's disease: the SuPREMe-CD study -a randomized clinical trial Inclusion of the mesentery in Ileocolic resection for Crohn's disease is associated with reduced surgical recurrence cache = ./cache/cord-297857-ybqj8z1r.txt txt = ./txt/cord-297857-ybqj8z1r.txt === reduce.pl bib === id = cord-306577-gq6fss5l author = Hsueh, Wei title = Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts date = 2002-11-11 pages = extension = .txt mime = text/plain words = 8414 sentences = 453 flesch = 40 summary = Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. We developed a model of bowel necrosis in adult rats and mice by injecting endotoxin (lipopolysaccharide, LPS) [32] , PAF (platelet-activating factor, paf-acether) [33, 34] , tumor necrosis factor-␣ (TNF) [35] , or a combination of these agents. Experimental evidence strongly supports the role of PAF, LPS, and TNF in acute ischemic bowel necrosis and in the neonatal rat model of NEC. Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (PAF-acether) cache = ./cache/cord-306577-gq6fss5l.txt txt = ./txt/cord-306577-gq6fss5l.txt === reduce.pl bib === id = cord-283246-dj7teo89 author = Otsuka, Ryo title = Macrophage activation syndrome and COVID-19 date = 2020-08-06 pages = extension = .txt mime = text/plain words = 3224 sentences = 177 flesch = 37 summary = Still, it is possible that the causative virus for COVID-19, SARS-CoV-2, infect with particular types of cells such as endothelial vessels in the lung, or alveolar wall or macrophages. MAS is typified by markedly upregulated expression of pro-inflammatory cytokines, which is called "cytokine storm." Without any therapeutic intervention, this strong inflammation results in severe tissue injury and, ultimately, patient death. Thus, the commencement of local inflammation induced by SARS-CoV-2 infection activates macrophages at that site, spreading rapidly to the entire lung, possibly due to the abundant expression of virus entry receptors, ACE2 and TMPRSS2 [36] . Severe cases of COVID-19 are often observed with ARDS, representing the MAS-like clinical and laboratory features. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in cache = ./cache/cord-283246-dj7teo89.txt txt = ./txt/cord-283246-dj7teo89.txt === reduce.pl bib === id = cord-282242-5tkhjiwl author = Gómez-Laguna, J. title = Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus date = 2009-08-19 pages = extension = .txt mime = text/plain words = 3816 sentences = 206 flesch = 49 summary = title: Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Several studies have examined the role of cytokines in the pathogenesis of PRRS (Van Reeth and Nauwynck, 2000) ; however, it is not clear how cytokines participate in macrophage activation during PRRSV infection or how they regulate development of the immune response to the virus. The expression of IFN-g by macrophages and lymphocytes has been previously reported in the lung of PRRSV-infected pigs (Thanawongnuwech et al., 2003) . Therefore, the expression of IL-10 observed in the present study might be responsible for reduced expression of cytokines such as IFN-a, IFN-g, IL-12p40 and TNF-a, that in turn may impair prolonged viral replication in the lung of infected animals. cache = ./cache/cord-282242-5tkhjiwl.txt txt = ./txt/cord-282242-5tkhjiwl.txt === reduce.pl bib === id = cord-309619-glb2y82u author = Domingo, Pere title = The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19) date = 2020-07-29 pages = extension = .txt mime = text/plain words = 9353 sentences = 508 flesch = 40 summary = Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1–7)/Mas1R axis. SARS-CoV induces the signal transducer and activator of transcription 1 TACE TNF-a converting enzyme TBK1 TANK-binding kinase 1 TLR toll-like receptor TMPRSS2 type II transmembrane serine protease TNF-a tumor necrosis alpha TRAF3 TNF receptor-associated factor 3 XCR1 XCL1 (Chemokine [C motif] ligand 1) and XCL3 (Chemokine [C motif] ligand 3) receptor production of double-membrane vesicles that lack PRRs and can then replicate in these vesicles [18] . COVID-19 patients have high serum levels of inflammatory cytokines, including interleukin (IL)-2, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage SARS-CoV-2 infects primarily type II pneumocytes through binding to the ACE2 receptor. ACE2 = Angiotensin-converting enzyme 2; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2; Ang II = Angiotensin II; ROS = Reactive oxygen species; AT1R = Angiotensin 1 receptor; ADAM17 = A disintegrin and metalloproteinase domain 17; TNF-a = Tumor necrosis factor alpha; TMPRSS2 = transmembrane protease serine 2. cache = ./cache/cord-309619-glb2y82u.txt txt = ./txt/cord-309619-glb2y82u.txt === reduce.pl bib === id = cord-307813-elom30nx author = Yip, Tsz-Fung title = Advancements in Host-Based Interventions for Influenza Treatment date = 2018-07-10 pages = extension = .txt mime = text/plain words = 15075 sentences = 735 flesch = 38 summary = Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses. cache = ./cache/cord-307813-elom30nx.txt txt = ./txt/cord-307813-elom30nx.txt === reduce.pl bib === id = cord-302258-derq9b27 author = Zhang, Hui title = Effects of ubiquitin-proteasome inhibitor on the expression levels of TNF-α and TGF-β1 in mice with viral myocarditis date = 2019-08-14 pages = extension = .txt mime = text/plain words = 3444 sentences = 201 flesch = 56 summary = Effects of ubiquitin-proteasome system (UPS) inhibitor MG-132 on the expression levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in mice with viral myocarditis were investigated to analyze the correlation of myocardial tissue score of mice between TNF-α and TGF-β1. Mortality rates of each group were recorded and compared on day 8 of modeling, and heart specimens from the remaining mice were histopathologically examined and the expression of mRNA and protein of TNF-α and TGF-β1 in myocardial tissues were detected by western blot analysis. The expression levels of myocardial histopathological scores, mRNA and protein of TNF-α and TGF-β1 in the blank and control group were significantly lower than those in the VMC and the MG-132 group. At present, few studies have reported the role of UPS in the inflammatory reaction of VMC, so we explored the effect of ubiquitin-proteasome inhibitor MG-23 on the expression levels of serum TNF-α and TGF-β1 in CVB mice, in order to understand the inflammatory mechanism of VMC. cache = ./cache/cord-302258-derq9b27.txt txt = ./txt/cord-302258-derq9b27.txt === reduce.pl bib === id = cord-034340-3ksfpaf7 author = nan title = Proceedings of the 26th European Paediatric Rheumatology Congress: part 2: Virtual. 23 - 26 September 2020 date = 2020-10-28 pages = extension = .txt mime = text/plain words = 35088 sentences = 2148 flesch = 49 summary = Objectives: The current study was undertaken to evaluate sociodemographic and sociocultural features, parent behavior, the gestation and breastfeeding period, nutritional status of early childhood in our patients with JIA, and to determine their relationship with disease activity, damage index, remission time, and relapse rate. Methods: In the present study were included data 170 JIA(55 boys and 115 girls)aged from 2 to 17 years,who received scheduled vaccination before the age of 2 years and before JIA onset against measles,parotitis,diphtheria and rubella.Incomplete vaccination means the reduced number of vaccine to age.In all patients the Ig G anti-vaccine antibodies levels were detected with ELISA.JIA categories were:oligoarthritis -73,polyarthritis -61,systemic-16 and enthesitisrelated arthritis-20.Data presented with median and 25%>75% Results: Incomplete vaccination against MMR was in 50 (42%)diphtheria in 85 (50%) of the JIA patients. cache = ./cache/cord-034340-3ksfpaf7.txt txt = ./txt/cord-034340-3ksfpaf7.txt === reduce.pl bib === id = cord-313227-6zwkfzab author = Scala, Stefania title = Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs date = 2020-05-27 pages = extension = .txt mime = text/plain words = 3872 sentences = 202 flesch = 36 summary = Interestingly, in patients infected by SARS-COv-2, there is an increase in IL1β, IFNγ, IP10, and MCP1, probably leading to activated T-helper-1 (TH1) cell responses, and increased production of T-helper-2 (TH2) immunosuppressive cytokines, such as IL4 and IL10 (18) . Peripheral blood examinations on admission in the majority of patients with COVID-19 displayed lymphopenia, elevated infection-related biomarkers (i.e., procalcitonin, erythrocyte sedimentation rate, serum ferritin, and C-reactive protein) (20) and several elevated inflammatory cytokines (i.e., tumor necrosis factor (TNF)-α, interleukin (IL)-2R and IL-6). Despite markedly reducing virus titers, anti-S-IgG caused lung injury during the early stages of infection, impairing the wound-healing macrophage response and TGF-β production, while promoting pro inflammatory cytokine IL-8, MCP1 production, and inflammatory macrophage accumulation (22) . Another proteasome inhibitor, VR23, possess powerful antiinflammatory activity reducing IL-6 in synovial cells from RA patients, and improving LPS-induced acute lung injury by decreasing neutrophil migration, TNF-α secretion, and tissue inflammation in a mice model (52) . cache = ./cache/cord-313227-6zwkfzab.txt txt = ./txt/cord-313227-6zwkfzab.txt === reduce.pl bib === id = cord-306983-6w2fvtfy author = Wang, Siye title = Influenza Virus—Cytokine-Protease Cycle in the Pathogenesis of Vascular Hyperpermeability in Severe Influenza date = 2010-10-01 pages = extension = .txt mime = text/plain words = 3808 sentences = 223 flesch = 39 summary = Influenza A virus infection resulted in significant increases in TNF-α, IL-6, IL-1β, viral hemagglutininprocessing protease trypsin levels, and viral replication with vascular hyperpermeability in lung and brain in the first 6 days of infection. The present study reports several new observations: (1) proinflammatory cytokines, TNF-a, IL-1b, and IL-6, when upregulated by influenza A virus infection, induce trypsin expression in various organs and human endothelial cells; (2) the upregulated trypsin induces [Ca 2+ ] i mobilization via activation of the PAR-2, followed by loss of zonula occludens-1 and vascular hyperpermeability; (3) inhibitors of NF-kB and activator protein 1 effectively suppress the upregulation of proinflammatory cytokines and trypsin and improve the survival rates of infected mice. The present results allow us to propose a new mechanism of junctional permeability regulation: upregulated trypsin by influenza A virus and/or proinflammatory cytokines induces increase in [Ca 2+ ] i and loss of zonula occludens-1 in endothelial cells via PAR-2 signaling. cache = ./cache/cord-306983-6w2fvtfy.txt txt = ./txt/cord-306983-6w2fvtfy.txt === reduce.pl bib === id = cord-310942-191m0e65 author = Boga, Jose Antonio title = Beneficial actions of melatonin in the management of viral infections: a new use for this “molecular handyman”? date = 2012-04-18 pages = extension = .txt mime = text/plain words = 7208 sentences = 362 flesch = 32 summary = The potential protective mechanisms include melatonin acting as a free radical scavenger, an antioxidant enzyme inducer, a positive regulator of immune functions and an inhibitor of inflammation, as well as a regulator of programmed cell death (PCD) [ Table 2 ]. Melatonin treatment also caused a rise in protein expression of the nuclear factor erythroid 2 (Nrf2), a transcription factor that plays a critical role by binding to the antioxidant response element in the promoter region of a number of genes encoding for antioxidant and detoxifying enzymes in several types of cells and tissues [109] . Respiratory syncytial virus infection of human respiratory epithelial cells enhances inducible nitric oxide synthase gene expression Melatonin decreases nitric oxide production and lipid peroxidation and increases interleukin-1 beta in the brain of mice infected by the Venezuelan equine encephalomyelitis virus cache = ./cache/cord-310942-191m0e65.txt txt = ./txt/cord-310942-191m0e65.txt === reduce.pl bib === id = cord-022526-j9kg00qf author = Jones, Samuel L. title = Disorders of the Gastrointestinal System date = 2009-05-18 pages = extension = .txt mime = text/plain words = 108803 sentences = 5988 flesch = 38 summary = Examination of the cardiovascular system (heart, peripheral pulse, and mucous membranes), lungs, and abdomen is essential to detect clinical signs of systemic inflammation from endotoxemia, coagulation disorders, dehydration, ileus, shock, and other abnormalities resulting from injury to the small or large intestine. Several reports suggest the efficacy of cisapride in managing intestinal disease in horses, including the resolution of persistent large colon impaction, treatment of equine grass sickness, and as a preventative for POI in horses after small intestinal surgery (0.1 mg/kg body mass intramuscularly during the postoperative period). 9 Primary role-players in DPJ-associated ileus include peritoneal inflammation, inflammatory cell migration/activation within the muscularis, small intestinal mechanical distention, and effects of endotoxin absorption. Diarrhea probably results from the severe ulceration and inflammation of the large intestine, causing increased secretion of water, electrolytes, and protein and decreased absorption of fluid. cache = ./cache/cord-022526-j9kg00qf.txt txt = ./txt/cord-022526-j9kg00qf.txt === reduce.pl bib === id = cord-336432-tu00gffr author = Wang, Zhiyu title = Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide date = 2020-07-07 pages = extension = .txt mime = text/plain words = 6582 sentences = 358 flesch = 47 summary = In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Accordingly, we set out to identify a small molecule with the following properties: broad-spectrum anti-inflammatory mechanism of action targeting cytokines of innate immunity; low toxicity and excellent safety profile; chemically stable; easily stored and administered; able to be rapidly adopted in clinical settings worldwide; and, widespread availability with inexpensive and efficient means of production. A library of 1,136 small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. cache = ./cache/cord-336432-tu00gffr.txt txt = ./txt/cord-336432-tu00gffr.txt === reduce.pl bib === id = cord-301102-jbjysyqm author = Priestnall, Simon L. title = Quantification of mRNA encoding cytokines and chemokines and assessment of ciliary function in canine tracheal epithelium during infection with canine respiratory coronavirus (CRCoV) date = 2009-01-15 pages = extension = .txt mime = text/plain words = 6022 sentences = 296 flesch = 48 summary = title: Quantification of mRNA encoding cytokines and chemokines and assessment of ciliary function in canine tracheal epithelium during infection with canine respiratory coronavirus (CRCoV) This study aimed to quantify pro-inflammatory cytokine mRNAs following infection of canine air-interface tracheal cultures with CRCoV. This study aimed to quantify pro-inflammatory cytokine mRNAs following infection of canine air-interface tracheal cultures with CRCoV. The quantification of canine IL-6, IL-8 and TNF-a mRNA copies in CRCoV-inoculated cultures was presented as the logarithm of the fold change relative to control-inoculated cultures in the same dog at the same time point. In response to LPS, mRNA levels of TNF-a, IL-6 and IL-8 in cultures, were significantly increased from 24 h post-inoculation, relative to controls, indicating that the assay was sensitive enough to detect changes in cytokine mRNAs within this system. IHC revealed coronavirus antigen positive intra-cytoplasmic staining of ciliated epithelial and goblet cells within canine tracheas of both CRCoV-inoculated cultures and from naturally infected cases of CIRD. cache = ./cache/cord-301102-jbjysyqm.txt txt = ./txt/cord-301102-jbjysyqm.txt === reduce.pl bib === id = cord-316904-g7dli0a8 author = Chang, Hernan R. title = Role of cytokines in AIDS wasting date = 1998-12-31 pages = extension = .txt mime = text/plain words = 8300 sentences = 433 flesch = 40 summary = Indeed, although wasting is not universally observed in AIDS patients, the wasting syndrome in a human immunodeficiency virus (HIV)-seropositive individual is generally utilized to establish the diagnosis of AIDS 1 and is defined by a decrease in body mass greater than 10% in the absence of concomitant opportunistic infections, malignancies, and other identifiable causes of weight loss. 33 It is against this background presentation of the interacting factors contributing to malnutrition and functional impairment in HIVinfected patients-namely anorexia, malabsorption, hypermetabolism, lethargy, and impaired fat and protein metabolism-that the role of cytokines in the AIDS wasting syndrome is discussed in the following sections. In addition to their pleiotropic actions on many body systems, they could potentially contribute to the wasting and cachexia of AIDS by their ability to induce anorexia, alter energy expenditure, increase muscle proteolysis and net protein breakdown, and initiate various abnormalities of lipid metabolism. cache = ./cache/cord-316904-g7dli0a8.txt txt = ./txt/cord-316904-g7dli0a8.txt === reduce.pl bib === id = cord-309171-kgc7lgjp author = Dolinger, Michael T. title = Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab date = 2020-05-21 pages = extension = .txt mime = text/plain words = 1276 sentences = 80 flesch = 47 summary = We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn's disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-α) blockade. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn's disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. 2 We describe a pediatric patient recently diagnosed with Crohn's disease who developed severe COVID-19 infection successfully treated with infliximab. This is the first reported case of a patient with recently diagnosed Crohn's disease with suspected MIS-C temporally related to COVID-19 treated with infliximab to co-manage both entities. cache = ./cache/cord-309171-kgc7lgjp.txt txt = ./txt/cord-309171-kgc7lgjp.txt === reduce.pl bib === id = cord-324949-sqy03dks author = Poe, Francis L. title = N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2 date = 2020-05-30 pages = extension = .txt mime = text/plain words = 3485 sentences = 208 flesch = 47 summary = In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. Mediation of the viral load could occur through NAC's ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death. The pathogenic factors of SARS-CoV-2 that could possibly be mediated by NAC are (1) T cell exhaustion, which manifests as lower counts and decreased functional capacity of CD4+ and CD8+ cells; (2) pro-inflammatory state via increase in TNF-ɑ, IL1β, IL18; and (3) modulation of viral activity through increased glutathione. Mediation of the viral load could occur through the ability of NAC to increase cellular redox status by maximizing the rate limiting step of glutathione synthesis, and thereby decreasing the effects of virally induced oxidative stress and cell death. cache = ./cache/cord-324949-sqy03dks.txt txt = ./txt/cord-324949-sqy03dks.txt === reduce.pl bib === id = cord-322250-7kjakuyw author = He, Jia title = Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice date = 2020-07-02 pages = extension = .txt mime = text/plain words = 4895 sentences = 285 flesch = 46 summary = title: Anemoside B4 protects against Klebsiella pneumoniaeand influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)and influenza virus FM1 (FM1)-induced pneumonia mice model. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, significant increase was observed in the TNF-α (Fig. 3d, g) , IL-6 ( Fig. 3e, h) , IL-1β (Fig. 3f ) , and MPO (Fig. 3i) in the BALF and lung tissue samples collected from the KP-infected pneumonia mice, which were reversed by anemoside B4. Influenza virus FM1-infected pneumonia leads to an inflammatory storm, suggesting that many pro-inflammatory cytokines like TNF-α and IL-6 released into blood and lung tissue [28] [29] [30] . cache = ./cache/cord-322250-7kjakuyw.txt txt = ./txt/cord-322250-7kjakuyw.txt === reduce.pl bib === id = cord-308433-vrkdtrfz author = Roberts, Ceri A. title = TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells date = 2017-02-15 pages = extension = .txt mime = text/plain words = 7283 sentences = 409 flesch = 56 summary = Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. To investigate whether TNF blockade regulates IL-10 expression in different pro-inflammatory cytokine-producing CD4 + T cells, we isolated CD4 + T cells from PB of healthy donors and cocultured the cells with CD14 + monocytes and anti-CD3 mAb (100 ng/ml) in the absence or presence of the anti-TNF mAb adalimumab (1 µg/ml), as previously described (20) . cache = ./cache/cord-308433-vrkdtrfz.txt txt = ./txt/cord-308433-vrkdtrfz.txt === reduce.pl bib === id = cord-319121-et957lfl author = Mifflin, Lauren title = Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target date = 2020-07-15 pages = extension = .txt mime = text/plain words = 12596 sentences = 633 flesch = 34 summary = However, as researchers continued to delve into the mechanisms governed by RIPK1, it has become apparent that RIPK1 inhibitors may offer key therapeutic options that anti-TNF therapies do not: first, RIPK1 inhibitors are safe in the central nervous system (CNS) as RIPK1 kinase does not signal through TNFR2 which has a protective role in the CNS 7 ; second, RIPK1 participates in a broader set of pro-inflammatory activities than those restricted to TNF 8 ; third, RIPK1 is regulated by a distinct set of signalling molecules that are genetically implicated in human autoimmune and autoinflammatory diseases, as discussed below, and thus patient stratification may be important in conducting clinical trials of RIPK1 inhibitors. Mouse models with cell lineage-specific A20 deficiency phenocopy different human inflammatory diseases, suggesting an important role for A20 in restricting RIPK1 activation in multiple tissues ( showed increased levels of pro-inflammatory cytokines, such as TNF, IL-1β and IL-6, and demonstrated clinical improvement after treatment with anti-TNF or anti-IL-1β therapy. cache = ./cache/cord-319121-et957lfl.txt txt = ./txt/cord-319121-et957lfl.txt === reduce.pl bib === id = cord-317628-1inxq7t5 author = Cuccarese, Michael F. title = Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date = 2020-08-14 pages = extension = .txt mime = text/plain words = 9573 sentences = 487 flesch = 43 summary = We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. We used these capabilities to rapidly develop high-throughput-ready disease models for both SARS-CoV-2 viral infection and the resulting cytokine storm, and immediately launched large-scale drug screens that recapitulated known effective and ineffective therapies and, more importantly, identified several new potential treatments for both SARS-CoV-2 infection and COVID-19-associated cytokine storm. To define the model, we evaluated the effect of SARS-CoV-2 infection in multiple cell types, of which three resulted in robust phenoprints as compared to either mock infected or inactivated virus control populations: Calu3 (a lung adenocarcinoma line), Vero (an immortalized interferondeficient African green monkey kidney line 55 ), and primary Human Renal Cortical Epithelium (HRCE) (Fig. 5C, Fig. S6D ). cache = ./cache/cord-317628-1inxq7t5.txt txt = ./txt/cord-317628-1inxq7t5.txt === reduce.pl bib === id = cord-339272-trd6rkxw author = Chen, Na title = Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice date = 2013-04-24 pages = extension = .txt mime = text/plain words = 4313 sentences = 225 flesch = 47 summary = The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. LPS-induced ALI is considered a neutrophil-dependent ALI that contributes to local recruitment and activation of neutrophils [8] ; the release of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6; and the formation of reactive oxygen and nitrogen species [9] [10] [11] . Therefore, with a mouse model of acute lung inflammation, the present study was undertaken to examine the effect of Prime-O-glucosylcimifugin on acute lung injury induced by intranasal instillation of LPS in BALB/c mice and investigate its possible mechanisms. Acute lung injury is characterized by systemic airway inflammatory response including cytokines (e.g., TNF-α, IL-6, IL-8), chemokines, pro-inflammatory mediators and a variety of cells, which regulate the migration and pulmonary infiltration of neutrophils into the interstitial tissue [34] . cache = ./cache/cord-339272-trd6rkxw.txt txt = ./txt/cord-339272-trd6rkxw.txt === reduce.pl bib === id = cord-006230-xta38e7j author = nan title = Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date = 2012-02-22 pages = extension = .txt mime = text/plain words = 135419 sentences = 7042 flesch = 43 summary = Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. cache = ./cache/cord-006230-xta38e7j.txt txt = ./txt/cord-006230-xta38e7j.txt === reduce.pl bib === id = cord-330549-ppuqvafd author = Christophi, George P. title = Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype date = 2009-04-27 pages = extension = .txt mime = text/plain words = 9832 sentences = 494 flesch = 43 summary = Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in normal subject macrophages resulted in an increased STAT/NF-κB activation and increased inflammatory gene expression to levels seen in macrophages of MS patients. Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in macrophages of normal human subjects using siRNA resulted in an increased activation of the above transcription factors and increased inflammatory gene expression to levels seen in macrophages of MS patients. In order to determine whether increased activation of STAT6, STAT1, and NF-κB in macrophages of MS patients relative to normal subjects corresponded to heightened expression of STAT6-, STAT1-, and NF-κB responsive genes, the mRNA levels of several genes were quantified following 18-hour treatment with several cytokines (Figure 6 ). cache = ./cache/cord-330549-ppuqvafd.txt txt = ./txt/cord-330549-ppuqvafd.txt === reduce.pl bib === id = cord-295745-iw3ftw3h author = Gershoni, Jonathan M title = Molecular decoys: antidotes, therapeutics and immunomodulators date = 2008-11-18 pages = extension = .txt mime = text/plain words = 5546 sentences = 276 flesch = 42 summary = Decoys not only provide the means to fine tune the regulation of these phenomena; they also serve as potential leads for the development of recombinant anti-toxins, anti-viral agents and novel therapeutics for combating cancer and inflammatory disease. For almost every membrane receptor of cytokines, growth factors and cell adhesins, soluble versions were found to be naturally produced by cells; hence 'natural decoys' that function as modifiers of the potent stimulants and regulators of inflammation and immune response. Telovamer, a soluble, high molecular weight anionic polymer represents a 'functional decoy' able to bind and neutralize both Toxin A and Toxin B of Clostridium difficile yet is not derived from the natural receptor for these toxins. Nature produces such soluble receptors in order to crucially regulate immune responses towards cancer and infection as well as inflammation in general (Figure 1 ). This is particularly relevant for chemokine receptors whose decoys persist as membrane proteins that are effective in ligand binding but 'handicapped' in signal transduction. cache = ./cache/cord-295745-iw3ftw3h.txt txt = ./txt/cord-295745-iw3ftw3h.txt === reduce.pl bib === id = cord-333650-4towah1t author = Malmo, Jostein title = Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date = 2016-05-12 pages = extension = .txt mime = text/plain words = 4659 sentences = 250 flesch = 50 summary = Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. To determine the presence of antiviral cytokines in children infected with hMPV and controls, we initially investigated the expression of type I, II and III IFNs. Fig 1A shows that only A2 infected children had slightly elevated mRNA levels of the type I IFN-β compared to the controls. Fig 2 shows the mRNA expression of A) IκBα, a repressor gene induced by NF-κB activation [19] , B) IL-1β, C) IL-18 and D) NLRP3 in hMPV infected children and controls. A previous study comparing the expression of several inflammatory cytokines in hMPV, RSV and influenza virus, detected elevated levels of TNF-α, IL-6 and IL-1β protein in nasal washes from infants with RTI [9] . cache = ./cache/cord-333650-4towah1t.txt txt = ./txt/cord-333650-4towah1t.txt === reduce.pl bib === id = cord-332071-bqvn3ceq author = Lee, Jeong Seok title = Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 date = 2020-07-10 pages = extension = .txt mime = text/plain words = 7099 sentences = 412 flesch = 53 summary = In a murine model of SARS-CoV infection, a delayed, but considerable type I IFN (IFN-I) response CORONAVIRUS Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 (Page numbers not final at time of first release) 2 promotes the accumulation of monocytes-macrophages and the production of pro-inflammatory cytokines, resulting in lethal pneumonia with vascular leakage and impaired virusspecific T-cell responses (10) . To examine the host immune responses in a cell type-specific manner, we subjected 59,572 cells to t-distributed stochastic neighbor embedding (tSNE) based on highly variable genes using the Seurat package (17) and identified 22 different clusters unbiased by patients or experimental batches of scRNA-seq (Fig. 1A, Fig. S1D ). First, we combined both mild and severe COVID-19 as a COVID-19 group and identified disease-specific changes in genes for each cell type compared to the healthy donor group using model-based analysis of single cell transcriptomics (MAST) (18) . cache = ./cache/cord-332071-bqvn3ceq.txt txt = ./txt/cord-332071-bqvn3ceq.txt === reduce.pl bib === id = cord-351310-6p42b144 author = Bohr, Adam title = Treatment of acute lung inflammation by pulmonary delivery of anti-TNF-α siRNA with PAMAM dendrimers in a murine model date = 2020-08-13 pages = extension = .txt mime = text/plain words = 4342 sentences = 263 flesch = 56 summary = In this study, commercially available generation 3 poly(amidoamine) (PAMAM) dendrimer was investigated for pulmonary delivery of siRNA directed against tumor necrosis factor (TNF) α for the treatment of acute lung inflammation. Delivery efficiency was assessed in vitro in the RAW264.7 macrophage cell line activated with lipopolysaccharide (LPS), and efficacy was evaluated in vivo in a murine model of LPS-induced lung inflammation upon pre-treatment with TNF-α siRNA. Also in vivo, the PAMAM dendriplexes induced efficacious TNF-α siRNA inhibition, as compared to non-complexed siRNA, upon pulmonary administration to mice with LPS-induced lung inflammation. In this study, we investigated generation 3 PAMAM dendrimers as transfection agents for pulmonary delivery of siRNA targeting TNF-α and examined their efficacy and safety in a murine acute lung inflammation model. Generation 3 PAMAM dendrimers were selected because they display very good efficiency for dendriplex formation They were prepared at different dendrimer-siRNA ratios and were characterized in vitro and in vivo concerning complexation, cellular uptake, cytotoxicity, in vitro transfection efficiency and in vivo therapeutic efficacy at the RNA and protein levels, respectively. cache = ./cache/cord-351310-6p42b144.txt txt = ./txt/cord-351310-6p42b144.txt === reduce.pl bib === id = cord-323553-bukm9m9q author = Song, Woo-Jin title = Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice date = 2019-08-31 pages = extension = .txt mime = text/plain words = 4238 sentences = 256 flesch = 52 summary = title: Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice Mesenchymal stem cells (MSCs), which release immunomodulatory factors such as tumor necrosis factor-α (TNF-α)-induced gene/protein 6 (TSG-6) and prostaglandin E2 (PGE2), have been suggested as an alternative therapeutic option for IBD treatment in veterinary medicine. (C) Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α released higher concentrations of immunomodulatory factors such as TSG-6 and PGE2 compared to levels released by naive cAT-MSCs. Results are shown as the mean ± standard deviation of three independent experiments. Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α showed enhanced therapeutic effects on mice with dextran sodium sulfate (DSS)-induced colitis. Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α showed enhanced therapeutic effects on mice with dinitrobenzene sulfonic acid (DNBS)-induced colitis. cache = ./cache/cord-323553-bukm9m9q.txt txt = ./txt/cord-323553-bukm9m9q.txt === reduce.pl bib === id = cord-346669-7n75m669 author = Wang, Shixin title = Roles of TNF-α gene polymorphisms in the occurrence and progress of SARS-Cov infection: A case-control study date = 2008-02-29 pages = extension = .txt mime = text/plain words = 3814 sentences = 200 flesch = 53 summary = This study was to investigate the relationship between tumor necrosis factor (TNF)-α gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. METHODS: The association between genetic polymorphisms of TNF-α gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-α gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. In this paper, we aimed to study whether polymorphisms in TNF-α promoter region were associated with SARS-CoV infection, development, and progression of interstitial lung fibrosis and femoral head necrosis in cure SARS patients. Considered that the progression of interstitial lung fibrosis or femoral head necrosis may be affected by hormone therapy, hormone using dosage, method and lasting period were considered in this study when analyzing the associations between gene polymorphisms with disease. cache = ./cache/cord-346669-7n75m669.txt txt = ./txt/cord-346669-7n75m669.txt === reduce.pl bib === id = cord-348391-xytmq2f2 author = Wyganowska-Swiatkowska, Marzena title = Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review date = 2020-06-30 pages = extension = .txt mime = text/plain words = 8077 sentences = 461 flesch = 41 summary = While long term proteinase and ACE-2 inhibition could be detrimental to cellular function and bodily homeostasis, targeted treatment partially reducing the effectiveness of coronavirus S protein attachment to the ACE2 or to the priming proteinase could have the potential to drop the SARS-CoV-2 viral load before a state of septic shock is reached at the peak of infection. Aspalathin and nothofagin extracted from Rooibos have been shown to effectively inhibit LPS-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules [124] . The effect and mechanism of salidroside on sepsis-induced acute lung injury is mediated by the inhibition of inflammatory responses and HMGB1 production in bacterial LPS-treated macrophages and mice. Study has shown that pelargonidin (PEL) had effectively inhibited LPS-induced release of HMGB1 and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. cache = ./cache/cord-348391-xytmq2f2.txt txt = ./txt/cord-348391-xytmq2f2.txt === reduce.pl bib === id = cord-354492-6r6qs4pp author = Messina, Giovanni title = Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work date = 2020-04-28 pages = extension = .txt mime = text/plain words = 6880 sentences = 355 flesch = 38 summary = Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes. In human infections with highly virulent respiratory viruses-such as avian influenza H5N1, H7N9, Severe Acute Respiratory Syndrome (SARS) coronavirus, and Coronavirus Disease-19 (COVID-19)-immunopathogenesis caused by the overproduction of pro-inflammatory cytokines may play an essential role in disease progression and mortality [3] . Finally, considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a modification of the dietary regimen in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of the patients, improving their outcomes. cache = ./cache/cord-354492-6r6qs4pp.txt txt = ./txt/cord-354492-6r6qs4pp.txt === reduce.pl bib === id = cord-353887-f4yd7guj author = Tang, Yujun title = Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies date = 2020-07-10 pages = extension = .txt mime = text/plain words = 8532 sentences = 461 flesch = 44 summary = Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients. In this review, we referred COVID-19 associated cytokine storm as the patients who are severely ill along with a high concentration of pro-inflammatory cytokines. The innate and adaptive immune responses activated by SARS-CoV-2 infection lead to uncontrolled inflammatory responses and ultimately cause the cytokine storm (14) . MERS-CoV infects the cells mentioned above to induce delayed (but increased) levels of pro-inflammatory cytokines (e.g., IL-2) and chemokines (e.g., CCL2, CCL3) (27, 30) . Although SARS-CoV is abortive in macrophages and DCs, the virus induces an increase in levels of pro-inflammatory cytokines and chemokines (31, 32) . A comment and a meta-analysis, which mainly bases on the evidence of SARS and MERS (64, 65) , stated that corticosteroid would increase mortality and delayed clearance of viral in coronavirus infection diseases. cache = ./cache/cord-353887-f4yd7guj.txt txt = ./txt/cord-353887-f4yd7guj.txt === reduce.pl bib === id = cord-336510-qzm9wgde author = Ellermann-Eriksen, Svend title = Macrophages and cytokines in the early defence against herpes simplex virus date = 2005-08-03 pages = extension = .txt mime = text/plain words = 20036 sentences = 986 flesch = 46 summary = In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. Generally the type I IFNs exhibit a huge range of biological effects, such as antiviral and antiproliferative effects, stimulation of immune cells such as T cells, natural killer (NK) cells, monocytes, macrophages, and dendritic cells, increased expression of MHC-I, activation of pro-apoptotic genes and inhibition of anti-apoptotic mechanisms, modulation of cellular differentiation, and inhibition of angiogenesis [171] . Effect of IL-4 and IL-13 on IFN-gamma-induced production of nitric oxide in mouse macrophages infected with herpes simplex virus type 2 Herpes Simplex virus type 1-induced interferon production and activation of natural killer cells in mice NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages cache = ./cache/cord-336510-qzm9wgde.txt txt = ./txt/cord-336510-qzm9wgde.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-351387-i0zamkpd author = Witte, Katrin title = The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date = 2015-09-25 pages = extension = .txt mime = text/plain words = 4360 sentences = 220 flesch = 49 summary = In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. In the first setting, PBMCs were stimulated with EPs 7630 (3 and 30 μg/ml), Escherichia coli 0127:B8 lipopolysaccharide (TLR4 ligand; 100 ng/ml; Sigma-Aldrich), polyinosinic-polycytidylic acid [poly (I:C); 10 μg/ml; Sigma-Aldrich], a cytokine mixture of IL-1β, IL-2 and IL-12 (10 ng/ml each; R&D systems), anti-CD3 (Orthoclone; Cilag) and anti-CD28 (R&D systems) monoclonal antibodies (1 μg/ml each), or were left without specific treatment (0.1% ethanol as solvent control) for 4 and 24 h, before cell culture supernatant was recovered for ELISA cytokine production analysis. Our data show that EPs 7630 strongly and dose-dependently induced the production of the pro-inflammatory cytokines TNF-α and IL-6 in human blood immune cells. cache = ./cache/cord-351387-i0zamkpd.txt txt = ./txt/cord-351387-i0zamkpd.txt === reduce.pl bib === id = cord-340741-bhxm4zua author = Nayak, Tapas Kumar title = P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date = 2019-04-12 pages = extension = .txt mime = text/plain words = 8025 sentences = 394 flesch = 48 summary = title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. In summary, for the first time it has been shown that CHIKV triggers robust TNF production (a key mediator of CHIKV induced inflammation) in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and viral protein nsP2 interacts with both the MAPKs during infection. cache = ./cache/cord-340741-bhxm4zua.txt txt = ./txt/cord-340741-bhxm4zua.txt === reduce.pl bib === id = cord-347298-7kqrl3rv author = Hedger, M.P. title = Immunology of the Testis and Male Reproductive Tract date = 2010-07-12 pages = extension = .txt mime = text/plain words = 21168 sentences = 1000 flesch = 46 summary = Thus, it appears unlikely that a lack of APCs is a contributing factor in testicular immune privilege, although differences in the number and distribution of MHC class II-expressing cells in the interstitial tissue of different species or strains may help to explain differences in susceptibility to autoimmune orchitis (Flickinger et al. Moreover, while inhibition of Leydig cell steroidogenesis during inflammation may involve indirect effects at the level of the pituitary, or the actions of inflammatory mediators produced by the testicular macrophages and Sertoli cells, there is evidence that these cells can also respond directly to TLR ligands (Bhushan et al. Activation of p38/Jnk is implicated in the stimulation of proliferation by immature Sertoli cells and the regulation of blood-testis barrier dynamics, steroidogenesis, and multiple inflammatory responses, including the production of IL6, iNOS, monocyte chemoattractant protein 1, and leukocyte adhesion molecules, in the mature Sertoli cell (De Cesaris et al. cache = ./cache/cord-347298-7kqrl3rv.txt txt = ./txt/cord-347298-7kqrl3rv.txt === reduce.pl bib === id = cord-344204-qq2vqzc2 author = Hariharan, Apurva title = The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients date = 2020-11-07 pages = extension = .txt mime = text/plain words = 5647 sentences = 307 flesch = 47 summary = Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a "cytokine storm" causing inflammatory response and destruction, mainly affecting the lungs. Immunomodulation at the level of NF-κB activation and inhibitors of NF-κB (IκB) degradation along with TNF-α inhibition will potentially result in a reduction in the cytokine storm and alleviate the severity of COVID-19. During previous coronavirus outbreaks, such as SARS-CoV and the Middle East Respiratory syndrome coronavirus (MERS-CoV) , it was reported that viral proteins such as nsp1, nsp3a, nsp7a, spike, and nucleocapsid protein all caused excessive NF-κB activation, possibly contributing to severe disease and high case-fatality rate (DeDiego et al. Herein, we review current literature on the effect of SARS-nCoV-2 infection on NF-κB activation and discuss the potential therapeutic role of inhibitors of this pathway in the treatment of COVID-19. cache = ./cache/cord-344204-qq2vqzc2.txt txt = ./txt/cord-344204-qq2vqzc2.txt === reduce.pl bib === id = cord-341667-ayl71jpc author = Van Reeth, Kristien title = Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans? date = 1998-04-17 pages = extension = .txt mime = text/plain words = 1959 sentences = 121 flesch = 48 summary = Biologically active interferon-a, tumor necrosis factor-a (TNF-a), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Biologically active interferon-a, tumor necrosis factor-a (TNF-a), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Levels of the three cytokines were significantly higher 18 -24 h after inoculation than at 48 -72 h after inoculation (P õ Clinical responses, influenza virus titers, BAL cell numbers, percentage of neutrophils, and cytokine titers of individual pigs .016 for all three cytokines). On histopathology, bronchi/bronchioli and, to a lesser degree, alveoli showed epithelial necrosis and To our knowledge, this is the first demonstration of influenza virus -induced TNF-a and IL-1 in BAL fluids of a natural virus massive neutrophil infiltration at 18 -24 h after inoculation. cache = ./cache/cord-341667-ayl71jpc.txt txt = ./txt/cord-341667-ayl71jpc.txt === reduce.pl bib === === reduce.pl bib === id = cord-354765-abayh871 author = Graham, R. S. title = Calming the Cytokine Storm - Splenic Ultrasound for Treating Inflammatory Disorders and Potentially COVID-19 date = 2020-07-17 pages = extension = .txt mime = text/plain words = 8835 sentences = 400 flesch = 42 summary = Here, we show results from the first in-human trials using non-invasive ultrasound stimulation of the spleen to reduce cytokine release in the context of both an acute response in healthy subjects and a chronic inflammatory condition in rheumatoid arthritis patients. In RA patients, we observed that daily splenic ultrasound stimulation results in reduction of blood-borne transcripts encoding for pro-inflammatory markers IL-1β, IL-8, and NFκB, as well as suppresses pathways involved in IL-6 and TNF production. Our additional pre-clinical animal data further demonstrates that in addition to dampening cytokine output and circulating monocyte invasiveness, prophylactic ultrasound activation of the splenic neuroimmune pathway results in enhanced antibody response upon exposure to an inflammatory antigen. By presenting the first in-human data from two independent studies using different devices and protocols, we have consistently demonstrated that non-invasive ultrasound stimulation of the spleen drives anti-inflammatory effects in the context of both an acute response in healthy subjects and a chronic inflammatory condition. cache = ./cache/cord-354765-abayh871.txt txt = ./txt/cord-354765-abayh871.txt === reduce.pl bib === id = cord-355847-1ru15s5a author = Convertino, Irma title = Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in COVID-19 patients date = 2020-06-11 pages = extension = .txt mime = text/plain words = 2936 sentences = 177 flesch = 45 summary = Several drugs, endowed with modulating activity on cytokine pathways, including anti-IL-6, anti-TNF, and Janus kinase (JAK) inhibitors, currently approved for the treatment of immune-mediated inflammatory diseases, have been suggested or could be yet taken into account for experimental use in COVID-19 patients with ARDS and/or pneumonia ( Fig. 1 ). In addition, a multicenter open-label randomized clinical trial is studying the benefit risk profile of siltuximab, as a single therapeutic option or in combination with anakinra, at a single dose of 11 mg/kg, in comparison with tocilizumab or anakinra, alone or in combination, in ARDS patients with COVID-19 [20] . Based on the results expected with tocilizumab and siltuximab, other anti-IL-6 drugs, currently approved for rheumatoid arthritis, namely sarilumab and sirukumab, could be studied in ARDS and pneumonia patients with COVID-19. Anti-JAK drugs (such as ruxolitinib, tofacitinib, baricitinib, oclacitinib, fedratinib, upadacitinib, and peficitinib) [39] should be considered also among the options for clinical investigations in COVID-19-related ARDS and pneumonia patients. cache = ./cache/cord-355847-1ru15s5a.txt txt = ./txt/cord-355847-1ru15s5a.txt === reduce.pl bib === id = cord-022888-dnsdg04n author = nan title = Poster Sessions date = 2009-08-19 pages = extension = .txt mime = text/plain words = 188640 sentences = 9313 flesch = 45 summary = Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. cache = ./cache/cord-022888-dnsdg04n.txt txt = ./txt/cord-022888-dnsdg04n.txt === reduce.pl bib === id = cord-015021-pol2qm74 author = nan title = Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date = 1994 pages = extension = .txt mime = text/plain words = 162327 sentences = 9379 flesch = 50 summary = It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events. cache = ./cache/cord-015021-pol2qm74.txt txt = ./txt/cord-015021-pol2qm74.txt === reduce.pl bib === id = cord-005814-ak5pq312 author = nan title = 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date = 1995 pages = extension = .txt mime = text/plain words = 179164 sentences = 12028 flesch = 56 summary = Results: In 5 patients with treated SS, 16 tests were performed (VL n=8; Dobu n=4; NA n=4 Method: Septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; MAP<70 mmHg) or the requirement for a noradrenaline (NA) infusion ~> 0.1 ~g/kg/min with a MAP _< 90mmHg. Cardiovascular support was limited to NA + dobutamine (DB), 546C88 was administered for up to 8 h at a fixed dose-rate of either i, 2.5, 5, 10 or 20 mg/kg/h iv. Methods: Fourteen cases were s~udied,their gestational age ranged from(27-32)ws.Continnous positive air way pressure was applied to six cases at Peep level from (3-6)cm H2o through nasal pronge,(group I),the other 8 cases were managed as routine,(group II).Blood gases, TcPO2,TcCo2,resp.rate,depth and pattern were monitored for assessment of tissue Oxygenation and ventilation, Results: Our rasults showed that early application of CPAP improve ventilation among (83.3%)of cases,while (16.7%)of cases need IMV.The cases of group II need IMV among (75%)of the studied cases during the second or the third day of life. cache = ./cache/cord-005814-ak5pq312.txt txt = ./txt/cord-005814-ak5pq312.txt === reduce.pl bib === id = cord-022940-atbjwpo5 author = nan title = Poster Sessions date = 2016-09-07 pages = extension = .txt mime = text/plain words = 241182 sentences = 12746 flesch = 47 summary = We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. cache = ./cache/cord-022940-atbjwpo5.txt txt = ./txt/cord-022940-atbjwpo5.txt === reduce.pl bib === id = cord-015394-uj7fe5y6 author = nan title = Scientific Abstracts date = 2008-12-23 pages = extension = .txt mime = text/plain words = 242330 sentences = 15267 flesch = 52 summary = Studies involving immunohistochemical analysis of normal ovaries have shown that granulosa cells express significantly higher levels of the activator protein-1 (AP-1) transcription factor, cFos compared to theca cells, where cFos expression is virtually absent. Following acute hypoxia (0.5% O2) for one to six hours, RhoA mRNA, total protein and activation (RhoA-GTP) levels were analysed, using semi-quantitative PCRs and western blot, and compared to normoxic non-pregnant human uterine smooth muscle control cells. Since there is an urgent need for non-invasive methods for determination of fetal (F) and placental (P) function, this study was designed to evaluate the genes differently and commonly expressed in P tissue and leukocytes in maternal (M) and F circulation.Material and Methods. The current study: 1) localized IL-6 mRNA levels in preeclamptic versus normal decidual sections; 2) evaluated mechanisms regulating IL-6 synthesis by targeting intracellular signaling pathways with specific inhibitors; 3) identified potential IL-6 targets by immunolocalizing the IL-6 receptor (IL-6R) to specific cell types in placental bed biopsies. cache = ./cache/cord-015394-uj7fe5y6.txt txt = ./txt/cord-015394-uj7fe5y6.txt ===== Reducing email addresses cord-023402-8qfmo6rq cord-023393-8nye3nc8 cord-023373-6wh1kb3p cord-023421-1d1gf7az cord-023431-zjyrhlxn cord-015147-h0o0yqv8 cord-023375-x4p187u7 cord-023441-q83y12sk cord-023392-axd0901z cord-023372-ft8cp9op cord-022631-s4n24xij cord-023374-87ob1exq cord-023394-ptfjxpo6 cord-023389-ilrp8vb7 cord-023433-d1b7qvhs cord-023410-eblcf902 cord-023407-s85g7g0x cord-023414-xxw5kptr cord-023387-tyeh14wz cord-023430-5zuewjv2 cord-023419-lnmc6vv5 cord-023411-iszb5qlk cord-023417-by18aczt cord-023388-btbf6wkg cord-023403-jzdrvfvr 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cord-267270-r17z4d8x cord-275730-650sjwyy cord-275413-e2rhioty cord-023445-c4tqioz1 cord-270414-gh9agf4x cord-256838-8rzibpbl cord-272695-wmzq4lkh cord-023415-hhvmsn5b cord-023443-pvz7dll9 cord-295683-eoxxal8v cord-023439-r04y1j22 cord-252725-e3pazjdi cord-271114-hv3gwvdi cord-023928-9a1w174h cord-271812-ldwb05xn cord-295523-5pv7kw6i cord-278339-6ddsj014 cord-259586-kep2dgaw cord-280599-7ixpqd5n cord-259367-2e998to9 cord-308008-s2t11l3h cord-301946-erzh30mt cord-300991-ipy24zxp cord-291076-p350i54m cord-279498-ez3yq7xi cord-297128-s5c9h4lm cord-297857-ybqj8z1r cord-306577-gq6fss5l cord-283246-dj7teo89 cord-282242-5tkhjiwl cord-309619-glb2y82u cord-307813-elom30nx cord-302258-derq9b27 cord-313227-6zwkfzab cord-306983-6w2fvtfy cord-310942-191m0e65 cord-336432-tu00gffr cord-301102-jbjysyqm cord-324949-sqy03dks cord-034340-3ksfpaf7 cord-309171-kgc7lgjp cord-316904-g7dli0a8 cord-322250-7kjakuyw cord-308433-vrkdtrfz cord-319121-et957lfl cord-317628-1inxq7t5 cord-339272-trd6rkxw cord-330549-ppuqvafd cord-295745-iw3ftw3h cord-332071-bqvn3ceq cord-333650-4towah1t cord-351310-6p42b144 cord-323553-bukm9m9q cord-346669-7n75m669 cord-348391-xytmq2f2 cord-354492-6r6qs4pp cord-353887-f4yd7guj cord-336510-qzm9wgde cord-335185-3qi29i6n cord-348855-lnltoj1n cord-351387-i0zamkpd cord-340741-bhxm4zua cord-341667-ayl71jpc cord-344204-qq2vqzc2 cord-337414-8ndkjs1i cord-354765-abayh871 cord-355847-1ru15s5a cord-347298-7kqrl3rv cord-022526-j9kg00qf cord-006230-xta38e7j cord-015021-pol2qm74 cord-005814-ak5pq312 cord-022888-dnsdg04n cord-022940-atbjwpo5 cord-015394-uj7fe5y6 Creating transaction Updating pos table Building ./etc/reader.txt cord-022940-atbjwpo5 cord-022888-dnsdg04n cord-005814-ak5pq312 cord-022888-dnsdg04n cord-015021-pol2qm74 cord-006770-m5wqk6rh number of items: 153 sum of words: 2,744,198 average size in words: 19,190 average readability score: 44 nouns: cells; patients; cell; expression; levels; results; protein; response; study; mice; activity; blood; role; activation; disease; treatment; production; factor; effects; group; infection; cytokines; effect; receptor; data; gene; cytokine; control; macrophages; analysis; type; proteins; responses; studies; system; virus; inflammation; time; methods; serum; cancer; tissue; lung; genes; development; function; stimulation; presence; molecules; acid verbs: using; induce; increased; shown; compared; found; associated; suggests; bound; including; activated; demonstrated; involves; reduced; investigated; observed; following; expressed; mediated; decreased; determined; indicates; inhibits; performed; resulting; produce; lead; cause; treat; measured; identified; develop; plays; studied; stimulated; detected; regulating; based; evaluate; reported; related; occurs; required; signalling; affect; revealed; obtained; known; contains; provide adjectives: inflammatory; human; immune; specific; high; anti; different; clinical; higher; significant; important; acute; normal; severe; low; dependent; endothelial; first; healthy; cellular; several; lower; non; present; viral; major; negative; positive; similar; early; multiple; new; many; molecular; vascular; respiratory; various; peripheral; pro; chronic; systemic; bacterial; large; total; intestinal; small; fetal; potential; functional; therapeutic adverbs: also; significantly; however; well; respectively; therefore; recently; furthermore; previously; moreover; directly; even; highly; often; especially; together; mainly; currently; still; less; alone; particularly; prior; now; interestingly; thereby; specifically; statistically; finally; potentially; approximately; strongly; later; frequently; differentially; usually; first; almost; additionally; rather; alternatively; subsequently; critically; yet; rapidly; far; probably; commonly; largely; clinically pronouns: we; it; their; our; its; i; they; them; one; us; itself; he; iga1; his; she; her; themselves; eph-4; you; me; him; il-1β; my; your; mrnas; interleukin-10; s; em; interleukin-15; igfbp2; himself; rhil-10; mrs; itsn2; il1-α; il-12; igmcic; ifnyr-/-mice; esat-6; e2f2-/-mice; crx-527; c183; ␣; ω-3; λr1; y€; ykl-40; y401; wi~; w@ proper nouns: TNF; IFN; T; MBL; IL-6; þ; mg; LPS; C; AE; CD4; IL-10; CD8; α; MS; II; der; University; HLA; IL-12; A; NK; SARS; PCR; IL-1; mRNA; RNA; B; S.; kg; DC; MHC; ELISA; E.; COVID-19; CSF; M; G; ¼; Fig; NF; IL-2; ICU; M.; I; GC; IL-18; IL-4; L; von keywords: tnf; cell; ifn; cd8; mbl; il-12; il-6; lps; covid-19; sars; patient; il-1; result; study; level; increase; effect; disease; pcr; dna; university; inflammatory; expression; elisa; virus; sepsis; rna; mouse; treatment; tnf-; response; protein; high; gene; sle; receptor; mhc; method; infection; il-4; il-10; human; cytokine; control; cd4; western; tgf; paf; mas; institute one topic; one dimension: cells file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733918/ titles(s): TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection three topics; one dimension: patients; cells; der file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104449/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169490/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143837/ titles(s): Scientific Abstracts | Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi | Schock five topics; three dimensions: patients cells results; cells cell il; il cells tnf; may cells endothelial; der und die file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104449/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169490/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551897/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158198/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143837/ titles(s): Scientific Abstracts | Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi | The role of interleukin-1 in general pathology | Disorders of the Gastrointestinal System | Schock Type: cord title: keyword-tnf-cord date: 2021-05-25 time: 17:03 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:tnf ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-013803-d1sbfibq author: Abu El-Asrar, Ahmed M. title: Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis date: 2019-12-05 words: 4665.0 sentences: 262.0 pages: flesch: 42.0 cache: ./cache/cord-013803-d1sbfibq.txt txt: ./txt/cord-013803-d1sbfibq.txt summary: title: Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis Previous studies demonstrated upregulation of proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, IL-15 and IL-17 in the aqueous humour (AH) samples from autoimmune uveitis patients [1] [2] [3] [4] [5] . For these reasons, we analyzed the AH from patients with active uveitis associated with four systemic inflammatory diseases (sarcoidosis, VKH disease, BD and HLA-B27-related inflammation) for the presence of sCD30, sCD163, sgp130, sIL-6R, sTNFRI and sTNFRII. Compared with controls, TNF-α, sCD163, sgp130, sIL-6R, sTNFRI and sTNFRII levels were significantly higher in BD and HLA-B-27-associated uveitis. Among the cytokine and soluble cytokine receptors analyzed, TNF-α and sCD30 differed significantly between patients with BD, sarcoidosis, HLA-B27-associated uveitis and VKH disease (p = 0.029; p = 0.001, respectively) (Fig. 1a) . abstract: PURPOSE: Soluble cytokine receptors are potential biomarkers for immune activation and have a promising potential as immunotherapeutic agents. We investigated the levels of soluble cytokine receptors in aqueous humour (AH) samples from patients with specific autoimmune uveitic entities. METHODS: Patients with active uveitis associated with Behçet’s disease (BD) (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt–Koyanagi–Harada (VKH) disease (n = 12) and control subjects (n = 9) were included. AH samples were analyzed with the use of multiplex assays for the proinflammatory cytokine tumour necrosis factor (TNF)-α and the soluble cytokine receptors sCD30, sCD163, sgp130, sIL-6 receptor-α (sIL-6R), sTNFRI and sTNFRII. RESULTS: TNF-α and soluble cytokine receptor AH levels were significantly higher in uveitis patients (n = 45) compared with controls (n = 9). When nongranulomatous uveitis (BD and HLA-B27-associated uveitis) was compared with granulomatous uveitis (sarcoidosis and VKH disease), the levels of sCD30 and sTNFRI/TNF-α and sTNFRII/TNF-α ratios were significantly enhanced in granulomatous uveitis. Finally, when comparing the profile in the specific uveitis entities, sCD30 levels were highest in patients with VKH disease. sgp130, sCD163, sIL-6R, sTNFRI and sTNFRII did not differ significantly between the four different clinical uveitic subgroups. CONCLUSIONS: Soluble cytokine receptors are significantly upregulated in autoimmune uveitis. CD30(+) T cells might contribute to the inflammatory process in granulomatous uveitis, particularly in VKH disease. Granulomatous uveitis is also characterized by significantly higher sTNFRs/TNF-α ratios than nongranulomatous uveitis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608430/ doi: 10.1038/s41433-019-0693-7 id: cord-023403-jzdrvfvr author: Ahlfors, E. title: Proliferation of Cells in the Oral Mucosa, the Ear Skin and the Regional Lymph Nodes in Mice Sensitized and Elicited with a Hapten date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: During contact sensitivity reaction, immune cells proliferate. In order to study the histological picture of these proliferation phases, we used a mouse model of contact sensitivity in the oral mucosa and on skin. We also used bromodeoxyuridin (BrdU, an analogue to thymidin) that is incorporated into the nucleus during cell replication. The hapten oxazolone (OXA) was used to sensitize and elicit the oral mucosa and/or the ear skin. Mice were killed at various times after elicitation, and unsensitized animals were also exposed to the hapten as controls. BrdU (25 mg/kg animal) was injected i.p. 2 h before the kill. Specimens from the oral mucosa, ear skin and submandibular and auricular lymph nodes were cut and fixed in 4% paraformaldehyde. They were then treated with acid and biotinylated anti‐BrdU antibody and developed using ABC‐kit and DAB. The analyses were performed using a Leica light microscope and the computer program analysis. In the oral mucosa, the frequency of proliferating cells were increasing during the observation period, 4–24 h after elicitation, regardless of site of sensitization. The proliferating cells were found mainly in the basal cell layer of the epithelium. Similar patterns were found in ear skin. The regional lymph nodes demonstrated a few scattered proliferating cells 4 h after elicitation. After 24 h, these cells were found frequently in the whole lymph node. Control animals exhibited considerable less proliferating cells at all times. We conclude that most proliferating cells were found 24 h after elicitation locally at the hapten‐exposed sites (the oral mucosa or the ear skin) as well as in the regional lymph nodes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169538/ doi: 10.1111/j.0300-9475.2004.01423ac.x id: cord-272695-wmzq4lkh author: Ahmed, Ahmed A. title: TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis date: 2020-05-13 words: 3813.0 sentences: 210.0 pages: flesch: 55.0 cache: ./cache/cord-272695-wmzq4lkh.txt txt: ./txt/cord-272695-wmzq4lkh.txt summary: This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. The amplified PCR product for TNF-α-308 was detected at 184 base pair as shown in Fig. 1 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls (supplementary file (Table 3 ). The amplified PCR product for IFN-γ + 874 were detected at 263 base pair as shown in Fig. 2 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls. abstract: BACKGROUND: Cutaneous leishmaniasis (CL) is well linked with immunogenetic factors. This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. METHODS: This is a case-control study involved 169 Saudi subjects with different L. species and 199 healthy controls from central region of Saudi Arabia. All subjects were characterized by TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms using PCR. RESULTS: Evaluation of genotyping and allelic frequency of TNF-α − 308 G/A in different L. species showed no significant association compared to controls (p > 0.05). Except, in cases of L. tropica that showed significantly higher TNF-α − 308 A versus G allele frequency (p = 0.0004). Evaluation of genotyping of IFN-γ + 874 (TT versus AA+AT recessive) and allelic frequency of IFN-γ + 874 (T versus A) showed significant higher in L. major and also in total CL cases as compared to healthy controls (p < 0.05). Furthermore, a strong association was observed between the susceptibility of L. major, L. tropica or total CL cases with synergistically combined high TNF-α 308/INF-γ 874 alleles. CONCLUSIONS: This is the first report that shows the gene polymorphisms of TNF-α − 308 G/A and IFN-γ + 874 A/T in Saudi patients with different L. species infections. Data showed that the TNF-α-308 G/A gene polymorphism is not associated with the susceptibility of CL in Saudi subjects. The only correlation was found in between A versus G allelic frequency in L. tropica. Importantly, IFN-γ + 874 A/T polymorphism was found to be associated with the susceptibility of L. major and also with total CL subjects. Moreover, data from synergistically combined high TNF-α 308/INF-γ 874 alleles strongly suggest their potential role in the susceptibility of leishmania infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32404058/ doi: 10.1186/s12881-020-01043-9 id: cord-023375-x4p187u7 author: Alitalo, A. title: Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi date: 2008-06-28 words: 17059.0 sentences: 877.0 pages: flesch: 46.0 cache: ./cache/cord-023375-x4p187u7.txt txt: ./txt/cord-023375-x4p187u7.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Serum resistance of Borrelia burgdorferi strains belonging to the B. afzelii and B. burgdorferi sensu stricto genospecies is dependent on binding of complement inhibitor factor H. We recently reported that factor H binding by B. burgdorferi is due to inducible expression of several approximately 20 kDa plasmid‐encoded, surface‐exposed lipoproteins related to OspE (e.g. ErpA, ErpP and P21). In addition, a second class of factor H‐binding proteins of approximately 27–35 kDa has been described. The OspE‐related lipoproteins are dramatically induced by B. burgdorferi during transmission from its tick vector into the mammalian host. The induction of OspE‐related lipoproteins during mammalian infection may play a key a role in the borrelial evasion of the host's immune system. The goal of the present study was to define the factor H‐binding regions of OspE‐related proteins using mutagenesis, peptide mapping and surface plasmon resonance analysis (Biacore). The combined studies revealed that the C‐terminal regions of both human and mouse factor H (SCRs 18–20) specifically bind to OspE‐related lipoproteins. We also found FHR‐1, whose C‐terminal SCRs 3–5 are homologous to SCRs 18–20 of factor H, to bind to OspE. Peptide mapping revealed five putative regions (designated I‐V) in OspE that could directly interact with factor H. Deleting the C‐terminal 15 amino acid residues from region V of P21 abolished its ability to bind factor H. At the same time, however, synthetic peptides corresponding to the C‐termini of OspE, P21 and ErpP did not inhibit factor H binding to OspE. Thus, the C‐terminal‐binding region V appears to be necessary but not sufficient for factor H binding. When a more specific mutation strategy was employed, where single amino acid residues in peptides spanning over the factor H‐binding regions were mutated to alanines, we observed that lysines in the factor H‐binding regions of OspE were required for factor H binding. The combined data have revealed that key lysine residues in OspE‐related lipoproteins and ionic interactions are crucial for factor H interactions. Furthermore, binding of OspE to the C‐termini of both mouse and human factor H suggests that Borrelia spirochetes utilize analogous complement resistance mechanisms in both rodents and man. In Borrelia garinii strains, which in in vitro analyses have been found to be sensitive to complement killing, differences in the OspE sequences as well as in the expression of factor H‐binding proteins may account for their susceptibility to serum lysis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169490/ doi: 10.1111/j.0300-9475.2004.01423aj.x id: cord-271114-hv3gwvdi author: Allam, Gamal title: Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms date: 2015-04-22 words: 5564.0 sentences: 313.0 pages: flesch: 52.0 cache: ./cache/cord-271114-hv3gwvdi.txt txt: ./txt/cord-271114-hv3gwvdi.txt summary: The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. Therefore, the primary aim of the current study was to investigate SNPs in the IL-1β -31 T/C (rs1143643), IL-6 -174 G/C (rs1800795), TNF-α -308 G/A (rs1800629), and IFN-γ +874 A/T (rs2430561) genes for their possible association with susceptibility to EOS in Saudi newborn infants. Newborns with sepsis had significantly higher serum levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) compared to both suspected and sepsis-free control groups (overall p value < 0.001, Table 1 ). abstract: In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5’ nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns. url: https://doi.org/10.5114/ceji.2015.50836 doi: 10.5114/ceji.2015.50836 id: cord-017470-sjk7a34u author: Arlati, Sergio title: Pathophysiology of Acute Illness and Injury date: 2018-06-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The pathophysiology of acute illness and injury recognizes three main effectors: infection, trauma, and ischemia-reperfusion injury. Each of them can act by itself or in combination with the other two in developing a systemic inflammatory reaction syndrome (SIRS) that is a generalized reaction to the morbid event. The time course of SIRS is variable and influenced by the number and severity of subsequent insults (e.g., reparative surgery, acquired hospital infections). It occurs simultaneously with a complex of counter-regulatory mechanisms (compensatory anti-inflammatory response syndrome, CARS) that limit the aggressive effects of SIRS. In adjunct, a progressive dysfunction of the acquired (lymphocytes) immune system develops with increased risk for immunoparalysis and associated infectious complications. Both humoral and cellular effectors participate to the development of SIRS and CARS. The most important humoral mediators are pro-inflammatory (IL-1β, IL-6, IL-8, IL-12) and anti-inflammatory (IL-4, IL-10) cytokines and chemokines, complement, leukotrienes, and PAF. Effector cells include neutrophils, monocytes, macrophages, lymphocytes, and endothelial cells. The endothelium is a key factor for production of remote organ damage as it exerts potent chemo-attracting effects on inflammatory cells, allows for leukocyte trafficking into tissues and organs, and promotes further inflammation by cytokines release. Moreover, the loss of vasoregulatory properties and the increased permeability contribute to the development of hypotension and tissue edema. Finally, the disseminated activation of the coagulation cascade causes the widespread deposition of microthrombi with resulting maldistribution of capillary blood flow and ultimately hypoxic cellular damage. This mechanism together with increased vascular permeability and vasodilation is responsible for the development of the multiple organ dysfunction syndrome (MODS). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122041/ doi: 10.1007/978-3-319-95114-0_2 id: cord-023411-iszb5qlk author: Astrinidou‐Vakaloudi, A. title: Presence of Helicobacter pylori Antibodies in Haemodialysis Patients date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Aim: Renal dysfunction may influence the colonization of gastric mucosa by urea‐splitting bacteria such as Helicobacter pylori, by increasing urea concentrations in the gastric juice. Our aim was to investigate the prevalence of H. pylori in patients with end‐stage renal disease (ESRD), receiving long‐term haemodialysis treatment. Methods: This study included 40 sera from patients with ESRD (29 male and 11 female) undergoing periodic haemodialysis; mean time of treatment was 42.6 months. Using ELISA technique, we investigated the presence of IgG and IgA antibodies against H. pylori as well as IgG CagA (antibodies specific for CagA(+) strains of H. pylori). Sera from 40 healthy blood donors were used as a control group. Results: H. pylori IgG antibodies were detected in 32 out of 40 (80%) patients in the dialysis group, while 31/40 (77.5%) tested positive for IgA. IgG CagA antibodies were present in 13 out of 40 (32.5%). Prevalence of H. pylori IgG, IgA and CagA IgG antibodies in the control group was 33, 7 and 15%, respectively. Conclusions: Although international data suggest that prevalence of H. pylori infection is the same in ESRD patients as in healthy individuals, in our study that seems not to be the case. The higher blood and gastric juice urea levels may be a risk factor (among many others), but more studies are required in order to understand the relation of H. pylori infection in this group of patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169550/ doi: 10.1111/j.0300-9475.2004.01423p.x id: cord-004919-d7tilk8v author: Baker, Rahaf title: Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab date: 2018-12-07 words: 1869.0 sentences: 105.0 pages: flesch: 42.0 cache: ./cache/cord-004919-d7tilk8v.txt txt: ./txt/cord-004919-d7tilk8v.txt summary: MAS is a potentially fatal syndrome that can present in patients with inflammatory conditions and is considered to be similar to hemophagocytic lymphohistiocytosis (HLH) [1, 2] . The most consistent diagnosis for our patient was MAS, as he had high persistent fevers without an infectious cause, lymphopenia and anemia, marked hyperferritinemia, hypertriglyceridemia, splenomegaly, and the presence of hemophagocytes on bone marrow biopsy. It is plausible that adalimumab triggered MAS in our patient as he presented at 2.5 months after initiation of adalimumab, which is consistent with the timeline from other case reports, and he had no obvious infection. Macrophage activation syndrome associated with etanercept in a child with systemic onset juvenile idiopathic arthritis Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis Visceral leishmaniasis and macrophagic activation syndrome in a patient with rheumatoid arthritis under treatment with adalimumab Possible macrophage activation syndrome following initiation of adalimumab in a patient with adult-onset still''s disease abstract: Macrophage activation syndrome (MAS) is a rare and potentially fatal condition characterized by excessive activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to overwhelming systemic inflammation and cytokine release. MAS has been reported with viral infections, autoimmune disorders, malignancies, and medications. We describe a case of a patient with axial spondyloarthritis (axSpA) treated with adalimumab, who presented with MAS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087649/ doi: 10.1007/s10067-018-4387-5 id: cord-013183-t25gecuw author: Beloumi, Dhekra title: Inflammatory Correlated Response in Two Lines of Rabbit Selected Divergently for Litter Size Environmental Variability date: 2020-09-01 words: 3575.0 sentences: 205.0 pages: flesch: 49.0 cache: ./cache/cord-013183-t25gecuw.txt txt: ./txt/cord-013183-t25gecuw.txt summary: The aim of this study was to evaluate the inflammatory response in the two lines of the experiment, in order to analyse the effect of selection on susceptibility to diseases after challenging to stressful situations, such as 24 h after the first delivery. The line selected for litter size heterogeneity (the high line) showed lower white blood leukocyte count (WBC; −0.87 × 10(3)/µL), lower percentage of basophils (−0.11%), higher concentration of TNF-α (+13.8 pg/mL), and greater concentration of CRP (+38.1 µg/mL) than the line selected for litter size homogeneity (the low line). The objective of this study was to evaluate the inflammatory response in the two lines of the divergent selection experiment for litter size environmental variance, in order to analyse the effect of selection on susceptibility to diseases after stressful situations, such as 24 h after the first delivery. abstract: SIMPLE SUMMARY: Animal welfare is a priority objective for the livestock industry. Litter size environmental variability has been related to environmental sensitivity. A divergent selection experiment for environmental variance of litter size variance was carried out successfully in rabbits over thirteen generations. The low line showed a lower inflammatory response and susceptibility to infectious disorders than the high line. In conclusion, the decrease of environmental sensitivity seems to increase the adaptation of the animal to the environment, and thus, its welfare. ABSTRACT: A divergent selection experiment for environmental variance of litter size variance was carried out in rabbits over thirteen generations. The aim of this study was to evaluate the inflammatory response in the two lines of the experiment, in order to analyse the effect of selection on susceptibility to diseases after challenging to stressful situations, such as 24 h after the first delivery. A total of 78 females were used in this study, 39 from each line. The line selected for litter size heterogeneity (the high line) showed lower white blood leukocyte count (WBC; −0.87 × 10(3)/µL), lower percentage of basophils (−0.11%), higher concentration of TNF-α (+13.8 pg/mL), and greater concentration of CRP (+38.1 µg/mL) than the line selected for litter size homogeneity (the low line). The high line had also higher concentrations of bilirubin, cholesterol, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) compared to the low line (difference between lines were +0.08 µmol/L, +0.14 µmol/L, +0.35 U/L and +2.4 U/L, respectively). The high line showed higher inflammatory response than the low line, in accordance with a larger susceptibility to infectious disorders. In conclusion, the line selected to increase litter size environmental variability seems to have poor capacity coping with environmental stressors. Therefore, selection for litter size environmental variability can be a useful way to improve animal welfare. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552264/ doi: 10.3390/ani10091540 id: cord-016960-xhzvp35g author: Berencsi, György title: Fetal and Neonatal Illnesses Caused or Influenced by Maternal Transplacental IgG and/or Therapeutic Antibodies Applied During Pregnancy date: 2012-03-08 words: 17693.0 sentences: 1045.0 pages: flesch: 42.0 cache: ./cache/cord-016960-xhzvp35g.txt txt: ./txt/cord-016960-xhzvp35g.txt summary: The importance of maternal anti-idiotypic antibodies are believed to prime the fetal immune system with epitopes of etiologic agents infected the mother during her whole life before pregnancy and delivery. Neonatal lupus is a model of passively acquired autoimmunity in which a mother-, who may have systemic lupus erythematosus (SLE) or Sj€ ogren''s syndrome (SS) or may be entirely asymptomatic-synthesizes antibodies to SSA/Ro and/or SSB/ La ribonucleoproteins that enter the fetal circulation via trophoblast FcRn receptors and presumably cause tissue injury (Lee 1990 ) as mentioned above. Teplizumab (CD3-specific, hOKT3g1-Ala-Ala), a humanized Fc mutated anti-CD3 monoclonal antibody induced tolerance, on the progression of type 1 diabetes in patients with recent-onset disease even 2 years after the first diagnosis (Herold et al. Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells abstract: The human fetus is protected by the mother’s antibodies. At the end of the pregnancy, the concentration of maternal antibodies is higher in the cord blood, than in the maternal circulation. Simultaneously, the immune system of the fetus begins to work and from the second trimester, fetal IgM is produced by the fetal immune system specific to microorganisms and antigens passing the maternal-fetal barrier. The same time the fetal immune system has to cope and develop tolerance and T(REG) cells to the maternal microchimeric cells, latent virus-carrier maternal cells and microorganisms transported through the maternal-fetal barrier. The maternal phenotypic inheritance may hide risks for the newborn, too. Antibody mediated enhancement results in dengue shock syndrome in the first 8 month of age of the baby. A series of pathologic maternal antibodies may elicit neonatal illnesses upon birth usually recovering during the first months of the life of the offspring. Certain antibodies, however, may impair the fetal or neonatal tissues or organs resulting prolonged recovery or initiating prolonged pathological processes of the children. The importance of maternal anti-idiotypic antibodies are believed to prime the fetal immune system with epitopes of etiologic agents infected the mother during her whole life before pregnancy and delivery. The chemotherapeutical and biological substances used for the therapy of the mother will be transcytosed into the fetal body during the last two trimesters of pregnancy. The long series of the therapeutic monoclonal antibodies and conjugates has not been tested systematically yet. The available data are summarised in this chapter. The innate immunity plays an important role in fetal defence. The concentration of interferon is relative high in the placenta. This is probably one reason, why the therapeutic interferon treatment of the mother does not impair the fetal development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121401/ doi: 10.1007/978-94-007-4216-1_9 id: cord-023390-5hcgdlmt author: Bhuvanath, S. title: Inflammatory Cytokine Modulation of Cancer Cell Proliferation date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Inflammatory cytokines have a critical role in modulation of both innate and adaptive immunity in response to foreign antigen. They also play an important role in anticancer immunity. For example, they can promote cell‐mediated immunity against cancer cells. With their immunostimulatory effects, these cytokines are being tested for cancer treatment in the form of DNA vaccine or adjuvant or therapeutic cytokines. Direct effect of these cytokines on cancer cell, however, is still unclear. In this project, we investigated whether IL‐1( and IL‐18 can modulate cancer cell proliferation. We employed a simple nonradioactive proliferation (MTT) assay and detection of lactate dehydrogenase (LDH) to test the effect of these recombinant human cytokines on various cancer cell lines, including breast cancer cell line (MCF‐7), oral carcinoma cell line (KB), colon cancer cell line (Caco‐2) and choriocarcinoma cell line (Jar). Cytokines used in this study had both inhibitory and stimulatory effect on cell proliferation. Findings in this project could provide an insight of cancer cell response to these cytokines and this could lead to a consideration on using cytokine as immunotherapy for cancer treatment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169513/ doi: 10.1111/j.0300-9475.2004.01423bi.x id: cord-310942-191m0e65 author: Boga, Jose Antonio title: Beneficial actions of melatonin in the management of viral infections: a new use for this “molecular handyman”? date: 2012-04-18 words: 7208.0 sentences: 362.0 pages: flesch: 32.0 cache: ./cache/cord-310942-191m0e65.txt txt: ./txt/cord-310942-191m0e65.txt summary: The potential protective mechanisms include melatonin acting as a free radical scavenger, an antioxidant enzyme inducer, a positive regulator of immune functions and an inhibitor of inflammation, as well as a regulator of programmed cell death (PCD) [ Table 2 ]. Melatonin treatment also caused a rise in protein expression of the nuclear factor erythroid 2 (Nrf2), a transcription factor that plays a critical role by binding to the antioxidant response element in the promoter region of a number of genes encoding for antioxidant and detoxifying enzymes in several types of cells and tissues [109] . Respiratory syncytial virus infection of human respiratory epithelial cells enhances inducible nitric oxide synthase gene expression Melatonin decreases nitric oxide production and lipid peroxidation and increases interleukin-1 beta in the brain of mice infected by the Venezuelan equine encephalomyelitis virus abstract: Melatonin (N‐acetyl‐5‐methoxytryptamine) is a multifunctional signaling molecule that has a variety of important functions. Numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. Clinical trials have shown that melatonin is efficient in preventing cell damage under acute (sepsis, asphyxia in newborns) and chronic states (metabolic and neurodegenerative diseases, cancer, inflammation, aging). The beneficial effects of melatonin can be explained by its properties as a potent antioxidant and antioxidant enzyme inducer, a regulator of apoptosis and a stimulator of immune functions. These effects support the use of melatonin in viral infections, which are often associated with inflammatory injury and increases in oxidative stress. In fact, melatonin has been used recently to treat several viral infections, which are summarized in this review. The role of melatonin in infections is also discussed herein. Copyright © 2012 John Wiley & Sons, Ltd. url: https://www.ncbi.nlm.nih.gov/pubmed/22511571/ doi: 10.1002/rmv.1714 id: cord-351310-6p42b144 author: Bohr, Adam title: Treatment of acute lung inflammation by pulmonary delivery of anti-TNF-α siRNA with PAMAM dendrimers in a murine model date: 2020-08-13 words: 4342.0 sentences: 263.0 pages: flesch: 56.0 cache: ./cache/cord-351310-6p42b144.txt txt: ./txt/cord-351310-6p42b144.txt summary: In this study, commercially available generation 3 poly(amidoamine) (PAMAM) dendrimer was investigated for pulmonary delivery of siRNA directed against tumor necrosis factor (TNF) α for the treatment of acute lung inflammation. Delivery efficiency was assessed in vitro in the RAW264.7 macrophage cell line activated with lipopolysaccharide (LPS), and efficacy was evaluated in vivo in a murine model of LPS-induced lung inflammation upon pre-treatment with TNF-α siRNA. Also in vivo, the PAMAM dendriplexes induced efficacious TNF-α siRNA inhibition, as compared to non-complexed siRNA, upon pulmonary administration to mice with LPS-induced lung inflammation. In this study, we investigated generation 3 PAMAM dendrimers as transfection agents for pulmonary delivery of siRNA targeting TNF-α and examined their efficacy and safety in a murine acute lung inflammation model. Generation 3 PAMAM dendrimers were selected because they display very good efficiency for dendriplex formation They were prepared at different dendrimer-siRNA ratios and were characterized in vitro and in vivo concerning complexation, cellular uptake, cytotoxicity, in vitro transfection efficiency and in vivo therapeutic efficacy at the RNA and protein levels, respectively. abstract: Abstract To improve the efficacy of nucleic acid-based therapeutics, e.g., small interfering RNA (siRNA), transfection agents are needed for efficient delivery into cells. Several classes of dendrimers have been found useful as transfection agents for the delivery of siRNA because their surface can readily be functionalized, and the size of the dendriplexes they form with siRNA is within the range of conventional nanomedicine. In this study, commercially available generation 3 poly(amidoamine) (PAMAM) dendrimer was investigated for pulmonary delivery of siRNA directed against tumor necrosis factor (TNF) α for the treatment of acute lung inflammation. Delivery efficiency was assessed in vitro in the RAW264.7 macrophage cell line activated with lipopolysaccharide (LPS), and efficacy was evaluated in vivo in a murine model of LPS-induced lung inflammation upon pre-treatment with TNF-α siRNA. The PAMAM dendrimer-siRNA complexes (dendriplexes) displayed strong siRNA condensation and high cellular uptake in macrophages compared with non-complexed siRNA. Q-PCR analyses showed that the dendriplexes mediated efficient and specific TNF-α silencing in vitro, as compared to non-complexed siRNA and dendriplexes with negative control siRNA. Also in vivo, the PAMAM dendriplexes induced efficacious TNF-α siRNA inhibition, as compared to non-complexed siRNA, upon pulmonary administration to mice with LPS-induced lung inflammation. Hence, these data suggest that PAMAM dendrimers are promising for the local delivery of TNF-α siRNA in the treatment of lung inflammation via pulmonary administration. url: https://www.ncbi.nlm.nih.gov/pubmed/32798665/ doi: 10.1016/j.ejpb.2020.08.009 id: cord-337414-8ndkjs1i author: Burgmaier, Gruscha title: Association of Increased Bcl‐2 Expression with Rescue from Tumor Necrosis Factor‐α‐Induced Cell Death in the Oligodendrocyte Cell Line OLN‐93 date: 2008-07-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract: The present study investigated the effects of flupirtine(Katadolon) on tumor necrosis factor (TNF)‐α‐mediated cell death andBcl‐2 expression in the permanent rat oligodendrocyte cell line OLN‐93 (OLNcells). TNF‐α (500 U/ml) induced apoptosis of OLN cells, which wasconfirmed by DNA fragmentation using an in situ end‐labeling technique andultrastructural analysis. Flupirtine significantly reduced the rate ofspontaneous cell death of OLN cells already at low concentrations;TNF‐α‐mediated apoptosis was suppressed only with higher concentrationsof flupirtine (100 μM). Expression of Bcl‐2 protein and mRNA inOLN cells was detected by immunocytochemistry, western blot, and RT‐PCR.Quantitative analysis of western blots revealed an ∼2.5‐fold up‐regulationof Bcl‐2 protein during TNF‐α treatment. Furthermore, addition of 10 or100 μM flupirtine before incubation with TNF‐α led to anapproximately threefold increase of Bcl‐2 expression. Exposure of OLN cells toflupirtine alone moderately augmented the expression of Bcl‐2 protein. Ourdata demonstrate that flupirtine up‐regulates the expression of Bcl‐2 proteinin OLN cells; this Bcl‐2 induction is associated with a reduced rate ofTNF‐α‐induced cell death. url: https://www.ncbi.nlm.nih.gov/pubmed/11080178/ doi: 10.1046/j.1471-4159.2000.0752270.x id: cord-006518-al94gxjw author: Calder, Philip C. title: n−3 Fatty acids, inflammation, and immunity— Relevance to postsurgical and critically III patients date: 2004 words: 10029.0 sentences: 518.0 pages: flesch: 43.0 cache: ./cache/cord-006518-al94gxjw.txt txt: ./txt/cord-006518-al94gxjw.txt summary: More recent studies showed that EPA did not induce TNF-α, IL-1β, or IL-1α (68) or IL-6 (69) in osteoblasts, and even countered the upregulating effect of arachidonic acid (68) ; that EPA and DHA could totally abolish cytokine-induced up-regulation of TNF-α, IL-1α, and IL-1β in cultured bovine chondrocytes and in human osteoarthritic cartilage explants (93, 94) ; and that EPA or fish oil inhibited endotoxin-induced TNF-α production by monocytes (111) (112) (113) (114) . Animal feeding studies with fish oil support the observations made in cell culture with respect to the effects of long-chain n-3 FA on NFκB activation and inflammatory cytokine production. Several studies in humans involving supplementation of the diet with fish oil have demonstrated decreased production of TNF-α, IL-1β, and IL-6 by endotoxin-stimulated monocytes or mononuclear cells (a mixture of lymphocytes and monocytes) (80) (81) (82) 119) . abstract: Excessive or inappropriate inflammation and immunosuppression are components of the response to surgery, trauma, injury, and infection in some individuals and these can lead, progressively, to sepsis and septic shock. The hyperinflammation is characterized by the production of inflammatory cytokines, arachidonic acid-derived eicosanoids, and other inflammatory mediators, while the immunosuppression is characterized by impairment of antigen presentation and of T helper cell type-1 responses. Long-chain n−3 FA from fish oil decrease the production of inflammatory cytokines and eicosanoids. They act both directly (by replacing arachidonic acid as an eicosanoid substrate and by inhibiting arachidonic acid metabolism) and indirectly (by altering the expression of inflammatory genes through effects on transcription factor activation). Thus, long-chain n−3 FA are potentially useful anti-inflammatory agents and may be of benefit in patients at risk of developing sepsis. As such, an emerging application of n−3 FA is in surgical or critically ill patients where they may be added to parenteral or enteral formulas. Parenteral or enteral nutrition including n−3 FA appears to preserve immune function better than standard formulas and appears to partly prevent some aspects of the inflammatory response. Studies to date are suggestive of clinical benefits from these approaches, especially in postsurgical patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101959/ doi: 10.1007/s11745-004-1342-z id: cord-001293-dfaxj3bv author: Cavaillon, Jean-Marc title: Is boosting the immune system in sepsis appropriate? date: 2014-03-24 words: 6238.0 sentences: 315.0 pages: flesch: 33.0 cache: ./cache/cord-001293-dfaxj3bv.txt txt: ./txt/cord-001293-dfaxj3bv.txt summary: In response to the failure of therapies aiming to target either the up-stream microbial activators or the effector molecules of the inflammatory cascade, a new concept has emerged of boosting the immune system to counter immunosuppression that develops in patients who survive the initial, hyperinflammatory period of sepsis [1] . One can conjecture that systemic treatment with IL-7 may act in undesired places, as illustrated by the following: IL-7 worsens graft-versus-host-induced tissue inflammation [81] ; favors inflammation in colitis [82] , contributes to arthritis severity [83] ; upregulates chemokines, IFNγ, macrophage recruitment, and lung inflammation [84] ; and, finally, increases production of inflammatory cytokines by monocytes and T cells [85] . Not only are PD-1-deficient mice markedly protected from the lethality of sepsis, accompanied by a decreased bacterial burden and suppressed inflammatory cytokine response [98] , but also blockade of PD-1 or PD-L1 improves survival in a murine model of sepsis, reverses immune dysfunction, inhibits lymphocyte apoptosis, and attenuates organ dysfunction [99] [100] [101] . abstract: A relative immunosuppression is observed in patients after sepsis, trauma, burns, or any severe insults. It is currently proposed that selected patients will benefit from treatment aimed at boosting their immune systems. However, the host immune response needs to be considered in context with pathogen-type, timing, and mainly tissue specificity. Indeed, the immune status of leukocytes is not universally decreased and their activated status in tissues contributes to organ failure. Accordingly, any new immune-stimulatory therapeutic intervention should take into consideration potentially deleterious effects in some situations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035855/ doi: 10.1186/cc13787 id: cord-316904-g7dli0a8 author: Chang, Hernan R. title: Role of cytokines in AIDS wasting date: 1998-12-31 words: 8300.0 sentences: 433.0 pages: flesch: 40.0 cache: ./cache/cord-316904-g7dli0a8.txt txt: ./txt/cord-316904-g7dli0a8.txt summary: Indeed, although wasting is not universally observed in AIDS patients, the wasting syndrome in a human immunodeficiency virus (HIV)-seropositive individual is generally utilized to establish the diagnosis of AIDS 1 and is defined by a decrease in body mass greater than 10% in the absence of concomitant opportunistic infections, malignancies, and other identifiable causes of weight loss. 33 It is against this background presentation of the interacting factors contributing to malnutrition and functional impairment in HIVinfected patients-namely anorexia, malabsorption, hypermetabolism, lethargy, and impaired fat and protein metabolism-that the role of cytokines in the AIDS wasting syndrome is discussed in the following sections. In addition to their pleiotropic actions on many body systems, they could potentially contribute to the wasting and cachexia of AIDS by their ability to induce anorexia, alter energy expenditure, increase muscle proteolysis and net protein breakdown, and initiate various abnormalities of lipid metabolism. abstract: Abstract There is now a large literature implicating cytokines in the development of wasting and cachexia commonly observed in a variety of pathophysiologic conditions. In the acquired immunodeficiency syndrome (AIDS), cytokines elicited by primary and secondary infections seem to exert subtle and sustained effects on behavioral, hormonal, and metabolic axes, and their combined effects on appetite and metabolism have been postulated to drive wasting. However, correlations of increased blood levels of a particular cytokine with wasting in AIDS have not been consistent observations, perhaps because cytokines act principally as paracrine and autocrine hormones, as well as indirectly by activating other systems. A better understanding of the mechanisms underlying the catabolic effects of cytokines is clearly needed if more efficacious strategies are to be developed for the prevention and treatment of wasting in AIDS. In this review we first examine the interacting factors contributing to the AIDS wasting syndrome. We then analyze the complex and overlapping role of cytokines in the pathophysiology of this condition, and put forward a number of hypotheses to explain some of the most important features of this syndrome. url: https://www.sciencedirect.com/science/article/pii/S0899900798001087 doi: 10.1016/s0899-9007(98)00108-7 id: cord-339272-trd6rkxw author: Chen, Na title: Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice date: 2013-04-24 words: 4313.0 sentences: 225.0 pages: flesch: 47.0 cache: ./cache/cord-339272-trd6rkxw.txt txt: ./txt/cord-339272-trd6rkxw.txt summary: The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. LPS-induced ALI is considered a neutrophil-dependent ALI that contributes to local recruitment and activation of neutrophils [8] ; the release of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6; and the formation of reactive oxygen and nitrogen species [9] [10] [11] . Therefore, with a mouse model of acute lung inflammation, the present study was undertaken to examine the effect of Prime-O-glucosylcimifugin on acute lung injury induced by intranasal instillation of LPS in BALB/c mice and investigate its possible mechanisms. Acute lung injury is characterized by systemic airway inflammatory response including cytokines (e.g., TNF-α, IL-6, IL-8), chemokines, pro-inflammatory mediators and a variety of cells, which regulate the migration and pulmonary infiltration of neutrophils into the interstitial tissue [34] . abstract: Prime-O-glucosylcimifugin is an active chromone isolated from Saposhnikovia root which has been reported to have various activities, such as anti-convulsant, anticancer, anti-inflammatory properties. The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. BALB/c mice received intraperitoneal injection of Prime-O-glucosylcimifugin 1 h before intranasal instillation (i.n.) of lipopolysaccharide (LPS). Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary histological changes were evaluated by hematoxylin–eosin, myeloperoxidase (MPO) activity in the lung tissue and lung wet/dry weight ratios were observed. Furthermore, the mitogen-activated protein kinases (MAPK) signaling pathway activation and the phosphorylation of IκBα protein were determined by Western blot analysis. Prime-O-glucosylcimifugin showed promising anti-inflammatory effect by inhibiting the activation of MAPK and NF-κB signaling pathway. url: https://doi.org/10.1016/j.intimp.2013.04.014 doi: 10.1016/j.intimp.2013.04.014 id: cord-023414-xxw5kptr author: Chistensen, H. R. title: Characterization of a Large Panel of Lactic Acid Bacteria Derived from the Human Gut for their Capacity to Polarize Dendritic Cell date: 2008-06-28 words: 16914.0 sentences: 872.0 pages: flesch: 46.0 cache: ./cache/cord-023414-xxw5kptr.txt txt: ./txt/cord-023414-xxw5kptr.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Dendritic cells (DCs) are the principal stimulators of naïve T helper (Th) cells and play a pivotal regulatory role in the Th1, Th2 and Treg cell balance. DCs are present in the gut mucosa and may thus be target for modulation by gut microbes, including ingested probiotics. Here, we tested the hypothesis that species of lactic acid bacteria, important members of the gut flora, differentially activate DC. A large panel of human gut‐derived Lactobacillus and Bifidobacterium spp. was screened for DC‐polarizing capacity by exposing bone marrow‐derived murine DC to lethally irradiated bacteria. Cytokines in culture supernatants and DC‐surface maturation markers were analysed. Substantial differences were found among strains in the capacity to induce interleukin‐12 (IL‐12) and tumour necrosis factor (TNF)‐α, while the differences for IL‐10 and IL‐6 were less pronounced. Bifidobacteria tended to be weak IL‐12 and TNF‐α inducers, while both strong and weak IL‐12 inducers were found among the strains of Lactobacillus. Remarkably, strains weak in IL‐12 induction inhibited IL‐12 and TNF‐α production induced by an otherwise strong cytokine‐inducing strain of Lactobacillus casei, while IL‐10 production remained unaltered. Selected strains were tested for induction of DC maturation markers. Those lactobacilli with greatest capacity to induce IL‐12 were most effective in upregulating surface MHC class II and CD86. Moreover, L. casei‐induced upregulation of CD86 was reduced in the presence of a weak IL‐12‐inducing L. reuteri. In conclusion, human Lactobacillus and Bifidobacterium spp. polarize differentially DC maturation. Thus, the potential exists for Th1/Th2/Treg‐driving capacities of the gut DC to be modulated according to composition of gut flora including ingested probiotics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169554/ doi: 10.1111/j.0300-9475.2004.01423ap.x id: cord-330549-ppuqvafd author: Christophi, George P. title: Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype date: 2009-04-27 words: 9832.0 sentences: 494.0 pages: flesch: 43.0 cache: ./cache/cord-330549-ppuqvafd.txt txt: ./txt/cord-330549-ppuqvafd.txt summary: Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in normal subject macrophages resulted in an increased STAT/NF-κB activation and increased inflammatory gene expression to levels seen in macrophages of MS patients. Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in macrophages of normal human subjects using siRNA resulted in an increased activation of the above transcription factors and increased inflammatory gene expression to levels seen in macrophages of MS patients. In order to determine whether increased activation of STAT6, STAT1, and NF-κB in macrophages of MS patients relative to normal subjects corresponded to heightened expression of STAT6-, STAT1-, and NF-κB responsive genes, the mRNA levels of several genes were quantified following 18-hour treatment with several cytokines (Figure 6 ). abstract: Recent studies in mice have demonstrated that the protein tyrosine phosphatase SHP-1 is a crucial negative regulator of pro-inflammatory cytokine signaling, TLR signaling, and inflammatory gene expression. Furthermore, mice genetically lacking SHP-1 (me/me) display a profound susceptibility to inflammatory CNS demyelination relative to wild type mice. In particular, SHP-1 deficiency may act predominantly in inflammatory macrophages to increase CNS demyelination as SHP-1-deficient macrophages display co-expression of inflammatory effector molecules and increased demyelinating activity in me/me mice. Recently, we reported that PBMCs of multiple sclerosis (MS) patients have a deficiency in SHP-1 expression relative to normal control subjects indicating that SHP-1 deficiency may play a similar role in MS as to that seen in mice. Therefore, it became essential to examine the specific expression and function of SHP-1 in macrophages from MS patients. Herein, we document that macrophages of MS patients have deficient SHP-1 protein and mRNA expression relative to those of normal control subjects. To examine functional consequences of the lower SHP-1, the activation of STAT6, STAT1, and NF-κB was quantified and macrophages of MS patients showed increased activation of these transcription factors. In accordance with this observation, several STAT6-, STAT1-, and NF-κB-responsive genes that mediate inflammatory demyelination were increased in macrophages of MS patients following cytokine and TLR agonist stimulation. Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in normal subject macrophages resulted in an increased STAT/NF-κB activation and increased inflammatory gene expression to levels seen in macrophages of MS patients. In conclusion, macrophages of MS patients display a deficiency of SHP-1 expression, heightened activation of STAT6, STAT1, and NF-κB and a corresponding inflammatory profile that may be important in controlling macrophage-mediated demyelination in MS. url: https://www.ncbi.nlm.nih.gov/pubmed/19398961/ doi: 10.1038/labinvest.2009.32 id: cord-018764-02l423mk author: Clark, Ian A. title: The molecular basis of paediatric malarial disease date: 2007 words: 10008.0 sentences: 485.0 pages: flesch: 35.0 cache: ./cache/cord-018764-02l423mk.txt txt: ./txt/cord-018764-02l423mk.txt summary: The influence of inflammatory cytokines on cellular function offers a molecular framework to explain the multiple clinical syndromes that are observed during acute malarial illness, and provides a fresh avenue of investigation for adjunct therapies to ameliorate the malarial disease process. The presence of hyperlactataemia, hypoglycaemia, and metabolic acidosis, all three consistent with a patient being forced to rely on anaerobic glycolysis for energy production, have provided a consensus that hypoxia is central to disease pathogenesis in falciparum malaria. Another inflammatory cytokine, macrophage inhibitory factor (MIF) that is increased in malaria, and induced by TNF, has been shown to cause dyserythropoiesis in in vitro studies on bone marrow cells [95, 96] . Although the sepsis world now discusses several origins for the lactate increase, including inflammation-induced mitochondrial dysfunction [97] , in falciparum malaria it is still generally attributed to a reduced oxygen supply, mostly through microvascular occlusion by sequestered parasitised erythrocytes [121] . abstract: Severe falciparum malaria is an acute systemic disease that can affect multiple organs, including those in which few parasites are found. The acute disease bears many similarities both clinically and, potentially, mechanistically, to the systemic diseases caused by bacteria, rickettsia, and viruses. Traditionally the morbidity and mortality associated with severe malarial disease has been explained in terms of mechanical obstruction to vascular flow by adherence to endothelium (termed sequestration) of erythrocytes containing mature-stage parasites. However, over the past few decades an alternative ‘cytokine theory of disease’ has also evolved, where malarial pathology is explained in terms of a balance between the pro- and anti-inflammatory cytokines. The final common pathway for this pro-inflammatory imbalance is believed to be a limitation in the supply and mitochondrial utilisation of energy to cells. Different patterns of ensuing energy depletion (both temporal and spatial) throughout the cells in the body present as different clinical syndromes. This chapter draws attention to the over-arching position that inflammatory cytokines are beginning to occupy in the pathogenesis of acute malaria and other acute infections. The influence of inflammatory cytokines on cellular function offers a molecular framework to explain the multiple clinical syndromes that are observed during acute malarial illness, and provides a fresh avenue of investigation for adjunct therapies to ameliorate the malarial disease process. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123729/ doi: 10.1007/978-3-7643-8099-1_9 id: cord-355847-1ru15s5a author: Convertino, Irma title: Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in COVID-19 patients date: 2020-06-11 words: 2936.0 sentences: 177.0 pages: flesch: 45.0 cache: ./cache/cord-355847-1ru15s5a.txt txt: ./txt/cord-355847-1ru15s5a.txt summary: Several drugs, endowed with modulating activity on cytokine pathways, including anti-IL-6, anti-TNF, and Janus kinase (JAK) inhibitors, currently approved for the treatment of immune-mediated inflammatory diseases, have been suggested or could be yet taken into account for experimental use in COVID-19 patients with ARDS and/or pneumonia ( Fig. 1 ). In addition, a multicenter open-label randomized clinical trial is studying the benefit risk profile of siltuximab, as a single therapeutic option or in combination with anakinra, at a single dose of 11 mg/kg, in comparison with tocilizumab or anakinra, alone or in combination, in ARDS patients with COVID-19 [20] . Based on the results expected with tocilizumab and siltuximab, other anti-IL-6 drugs, currently approved for rheumatoid arthritis, namely sarilumab and sirukumab, could be studied in ARDS and pneumonia patients with COVID-19. Anti-JAK drugs (such as ruxolitinib, tofacitinib, baricitinib, oclacitinib, fedratinib, upadacitinib, and peficitinib) [39] should be considered also among the options for clinical investigations in COVID-19-related ARDS and pneumonia patients. abstract: Sars-CoV-2 complications include pneumonia and acute respiratory distress syndrome (ARDS), which require intensive care unit admission. These conditions have rapidly overwhelmed healthcare systems, with detrimental effects on the quality of care and increased mortality. Social isolation strategies have been implemented worldwide with the aim of reducing hospital pressure. Among therapeutic strategies, the use of immunomodulating drugs, to improve prognosis, seems promising. Particularly, since pneumonia and ARDS are associated with a cytokine storm, drugs belonging to therapeutic classes as anti-IL-6, anti-TNF, and JAK inhibitors are currently studied. In this article, we discuss the potential advantages of the most promising pharmacological approaches. url: https://doi.org/10.1186/s13054-020-03020-3 doi: 10.1186/s13054-020-03020-3 id: cord-317628-1inxq7t5 author: Cuccarese, Michael F. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 words: 9573.0 sentences: 487.0 pages: flesch: 43.0 cache: ./cache/cord-317628-1inxq7t5.txt txt: ./txt/cord-317628-1inxq7t5.txt summary: We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. We used these capabilities to rapidly develop high-throughput-ready disease models for both SARS-CoV-2 viral infection and the resulting cytokine storm, and immediately launched large-scale drug screens that recapitulated known effective and ineffective therapies and, more importantly, identified several new potential treatments for both SARS-CoV-2 infection and COVID-19-associated cytokine storm. To define the model, we evaluated the effect of SARS-CoV-2 infection in multiple cell types, of which three resulted in robust phenoprints as compared to either mock infected or inactivated virus control populations: Calu3 (a lung adenocarcinoma line), Vero (an immortalized interferondeficient African green monkey kidney line 55 ), and primary Human Renal Cortical Epithelium (HRCE) (Fig. 5C, Fig. S6D ). abstract: Development of accurate disease models and discovery of immune-modulating drugs is challenged by the immune system’s highly interconnected and context-dependent nature. Here we apply deep-learning-driven analysis of cellular morphology to develop a scalable “phenomics” platform and demonstrate its ability to identify dose-dependent, high-dimensional relationships among and between immunomodulators, toxins, pathogens, genetic perturbations, and small and large molecules at scale. High-throughput screening on this platform demonstrates rapid identification and triage of hits for TGF-β- and TNF-α-driven phenotypes. We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. The presented library of images, deep learning features, and compound screening data from immune profiling and COVID-19 screens serves as a deep resource for immune biology and cellular-model drug discovery with immediate impact on the COVID-19 pandemic. url: https://doi.org/10.1101/2020.08.02.233064 doi: 10.1101/2020.08.02.233064 id: cord-309171-kgc7lgjp author: Dolinger, Michael T. title: Pediatric Crohn''s Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab date: 2020-05-21 words: 1276.0 sentences: 80.0 pages: flesch: 47.0 cache: ./cache/cord-309171-kgc7lgjp.txt txt: ./txt/cord-309171-kgc7lgjp.txt summary: We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn''s disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-α) blockade. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn''s disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. 2 We describe a pediatric patient recently diagnosed with Crohn''s disease who developed severe COVID-19 infection successfully treated with infliximab. This is the first reported case of a patient with recently diagnosed Crohn''s disease with suspected MIS-C temporally related to COVID-19 treated with infliximab to co-manage both entities. abstract: Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn's disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-α) blockade. The patient presented with five days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 PCR was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn's disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with MIS-C temporally related to COVID-19 requires further investigation. url: https://www.ncbi.nlm.nih.gov/pubmed/32452979/ doi: 10.1097/mpg.0000000000002809 id: cord-309619-glb2y82u author: Domingo, Pere title: The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19) date: 2020-07-29 words: 9353.0 sentences: 508.0 pages: flesch: 40.0 cache: ./cache/cord-309619-glb2y82u.txt txt: ./txt/cord-309619-glb2y82u.txt summary: Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1–7)/Mas1R axis. SARS-CoV induces the signal transducer and activator of transcription 1 TACE TNF-a converting enzyme TBK1 TANK-binding kinase 1 TLR toll-like receptor TMPRSS2 type II transmembrane serine protease TNF-a tumor necrosis alpha TRAF3 TNF receptor-associated factor 3 XCR1 XCL1 (Chemokine [C motif] ligand 1) and XCL3 (Chemokine [C motif] ligand 3) receptor production of double-membrane vesicles that lack PRRs and can then replicate in these vesicles [18] . COVID-19 patients have high serum levels of inflammatory cytokines, including interleukin (IL)-2, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage SARS-CoV-2 infects primarily type II pneumocytes through binding to the ACE2 receptor. ACE2 = Angiotensin-converting enzyme 2; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2; Ang II = Angiotensin II; ROS = Reactive oxygen species; AT1R = Angiotensin 1 receptor; ADAM17 = A disintegrin and metalloproteinase domain 17; TNF-a = Tumor necrosis factor alpha; TMPRSS2 = transmembrane protease serine 2. abstract: The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once. These are the viral loop, the hyperinflammatory loop, the non-canonical renin-angiotensin system (RAS) axis loop, and the hypercoagulation loop. Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1–7)/Mas1R axis. The viral feedback loop includes evading the host's innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response. The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(1–7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS. The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome. url: https://doi.org/10.1016/j.ebiom.2020.102887 doi: 10.1016/j.ebiom.2020.102887 id: cord-023441-q83y12sk author: Draborg, H. title: Recominant Expression and Immunological Characterization of House Dust Mite Allergen Der P 1 date: 2008-06-28 words: 16905.0 sentences: 868.0 pages: flesch: 46.0 cache: ./cache/cord-023441-q83y12sk.txt txt: ./txt/cord-023441-q83y12sk.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: The cysteine protease Der p1 from dust mite of the genus Dermatophagoides pteronyssinus is a major type I allergen. About 80% of house dust mite (HDM) allergic individuals are reactive to this protease in standard assays for detection of IgE. A curative treatment for atopic allergy is immunotherapy (IT) with HDM extracts which are complex mixtures occasionally resulting in anaphylactic reactions. Novozymes focuses on developing a recombinant variant of Der p1 which exhibit lowered risk of IgE‐mediated allergic reactions, while maintaining its ability to trigger proper Th‐cell responses. This may provide a safer alternative for specific IT of HDM allergy. A secreted recombinant form of pro‐Der p 1 expressed by Saccharamyces cerevisiae was obtained by fusion of the pro‐enzyme to a fungal signal peptide. The N‐glycosylation site of Der p1 was mutated resulting in a deglycosylated pro‐enzyme with a molecular mass of 35 kDa. Protein purification procedure was developed to obtain nearly pure Der p1 protein followed by determination of concentration by active‐site‐titration with the cysteine protease inhibitor E64. The deglycosylated recombinant pro‐Der p 1 revealed immunologic similarity to the native Der p 1 molecule when compared in basophile histamine release, IgE‐binding assays and T‐cell proliferation assays. By in silico epitope mapping of a modelled 3‐dimensional structure of Der p1, five putative IgG and IgE epitopes were predicted. By protein engineering, the predicted epitopes were removed one by one in Der p1 and screening for hypoallergenic variants was performed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169606/ doi: 10.1111/j.0300-9475.2004.01423ag.x id: cord-005983-2ascbu62 author: Eigler, A. title: Suppression der Synthese des Tumornekrosefaktors date: 2001 words: 2378.0 sentences: 302.0 pages: flesch: 41.0 cache: ./cache/cord-005983-2ascbu62.txt txt: ./txt/cord-005983-2ascbu62.txt summary: Klinische Studien aus den vergangenen 5 Jahren belegen die zentrale Rolle des Tumornekrosefaktors (TNF) im pathophysiologischen Geschehen der rheumatoiden Arthritis und des Morbus Crohn.Die vorliegende Arbeit gibt einen Überblick über die Regulation der Synthese und die vielfältigen Wirkungen dieses Zytokins.So wurden erhöhte TNF-Konzentrationen bei verschiedenen infektiösen und entzündlichen Erkrankungen sowie in Verbindung mit speziellen Therapien nachgewiesen.Darauf aufbauend werden experimentelle therapeutische Strategien zur Hemmung der TNF-Bildung dargestellt. In den folgenden Abschnitten wird näher auf Strategien zur Hemmung der TNF-Synthese eingegangen, die im Tierexperiment oder schon beim Menschen in klinischen Studien untersucht worden sind. Die entzündungshemmende Wirkung von cAMP-erhöhenden Substanzen wird jedoch nicht nur über eine Hemmung der TNF-Synthese vermittelt. Weiterhin konnte durch die Therapie mit Rolipram die Suppression der TNF-Synthese und ein Überlebensvorteil in einem Rattenmodell des ARDS gezeigt werden [40] . The specific type IV phosphodiesterase inhibitor rolipram suppresses tumor necrosis factor-α production by human mononuclear cells abstract: Klinische Studien aus den vergangenen 5 Jahren belegen die zentrale Rolle des Tumornekrosefaktors (TNF) im pathophysiologischen Geschehen der rheumatoiden Arthritis und des Morbus Crohn. Die vorliegende Arbeit gibt einen Überblick über die Regulation der Synthese und die vielfältigen Wirkungen dieses Zytokins. So wurden erhöhte TNF-Konzentrationen bei verschiedenen infektiösen und entzündlichen Erkrankungen sowie in Verbindung mit speziellen Therapien nachgewiesen. Darauf aufbauend werden experimentelle therapeutische Strategien zur Hemmung der TNF-Bildung dargestellt. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096082/ doi: 10.1007/s001080050721 id: cord-021266-afs9eb40 author: El Gendy, Fady M. title: The role of Tumor necrosis factor alpha −308 G>A promoter polymorphism in pediatric community acquired pneumonia date: 2020-02-10 words: 3756.0 sentences: 222.0 pages: flesch: 50.0 cache: ./cache/cord-021266-afs9eb40.txt txt: ./txt/cord-021266-afs9eb40.txt summary: Our objective was to evaluate the association of TNF-α gene −308 G>A polymorphism with susceptibility to, and severity of, community-acquired pneumonia (CAP). We found no significant association of alleles or genotypes with any indicators of CAP severity, including clinical severity scores, but we were not able to assess the influence of TNF-α polymorphism on mortality since none of our patients died. Consistent with our findings, genotyping of 77 children with respiratory syncytial virus infection revealed no association of TNF-α −308 G>A polymorphism with any of the clinical outcomes, including severity scores of lower respiratory illness, oxygen saturation, lengths of oxygen supplementation, intensive care unit (ICU) and hospital stays, and the presence or absence of pneumonia and otitis media [25] . However, another study of 277 Chinese adult patients with severe pneumonia-induced sepsis found that TNF-α "A" allele increased the risk of septic shock (OR = 4.28). abstract: BACKGROUND: Tumor necrosis factor alpha (TNF-α) −308 G>A promoter polymorphism might be associated with excessive production of the proinflammatory cytokine TNF-α, modulating host response to pulmonary infections. Our objective was to evaluate the association of TNF-α gene −308 G>A polymorphism with susceptibility to, and severity of, community-acquired pneumonia (CAP). RESULTS: This was a cross-sectional study including 45 Egyptian children hospitalized for CAP in addition to 45 healthy children who served as a control group. Pneumonia severity was assessed on admission by the World Health Organization (WHO) guidelines; Pediatric Respiratory Severity Score (PRESS) score; Predisposition, Infection, Response and Organ failure (PIROm) score; and Respiratory Index of Severity in Children (RISC) score. Genotyping of TNF-α polymorphism was performed to all individuals by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Patients were monitored till hospital discharge. Frequency of AG genotype was lower among patients compared with control [odds ratio (OR) and 95% confidence interval (CI) = 0.13 (0.03–0.63); p = 0.012]. Prevalence of genotypes AA+AG was lower among patients compared with controls [OR and 95% CI = 0.34 (0.12–0.99); p = 0,048]. The “A” allele prevalence was higher among controls, but no significant association was found with CAP [OR and 95% CI = 0.58 (0.25–1.35); p = 0.21]. When PRESS score was used to classify patients into “severe pneumonia” and “non-severe pneumonia,” no significant association of any of the alleles or genotypes with CAP severity was found. CONCLUSION: TNF-α −308 G>A polymorphism confers protection from pediatric CAP but is not associated with indicators of CAP severity. Larger studies are needed to confirm these findings in pediatric patients from different ethnicities. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149214/ doi: 10.1186/s43054-020-0019-1 id: cord-017639-wtc8bml5 author: El-Radhi, A. Sahib title: Pathogenesis of Fever date: 2019-01-02 words: 5141.0 sentences: 346.0 pages: flesch: 44.0 cache: ./cache/cord-017639-wtc8bml5.txt txt: ./txt/cord-017639-wtc8bml5.txt summary: The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. • Cytokines are proteins produced throughout the body, mainly by activated macrophages, monocytes and T cells to regulate the immune responses within the body, control inflammatory and haematopoietic processes and may induce fever. Pro-inflammatory cytokines (e.g. IL-1, IL-6, TNF-α, INF-γ, granulocytes-macrophages colony stimulating factor, GM-CSF) are responsible for initiating an effective defence against exogenous organisms (e.g. activating neutrophils). • Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. • Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. abstract: The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response. The hypothalamic thermoregulatory centre accomplishes heat production by inducing shivering and heat conservation through vasoconstriction. At an established degree, fever is regulated (even at a temperature of over 41.0 °C) and heat production approximates loss, as in health, though at a higher level of the set point. Therefore fever does not climb up relentlessly. In addition to the function as an endogenous pyrogen, IL-1 activates T-lymphocytes to produce various factors, such as INF and IL-2, which are vital for immune response. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever. The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the host’s survival during infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122269/ doi: 10.1007/978-3-319-92336-9_3 id: cord-336510-qzm9wgde author: Ellermann-Eriksen, Svend title: Macrophages and cytokines in the early defence against herpes simplex virus date: 2005-08-03 words: 20036.0 sentences: 986.0 pages: flesch: 46.0 cache: ./cache/cord-336510-qzm9wgde.txt txt: ./txt/cord-336510-qzm9wgde.txt summary: In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. Generally the type I IFNs exhibit a huge range of biological effects, such as antiviral and antiproliferative effects, stimulation of immune cells such as T cells, natural killer (NK) cells, monocytes, macrophages, and dendritic cells, increased expression of MHC-I, activation of pro-apoptotic genes and inhibition of anti-apoptotic mechanisms, modulation of cellular differentiation, and inhibition of angiogenesis [171] . Effect of IL-4 and IL-13 on IFN-gamma-induced production of nitric oxide in mouse macrophages infected with herpes simplex virus type 2 Herpes Simplex virus type 1-induced interferon production and activation of natural killer cells in mice NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages abstract: Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered. url: https://www.ncbi.nlm.nih.gov/pubmed/16076403/ doi: 10.1186/1743-422x-2-59 id: cord-256838-8rzibpbl author: Eng, Yi Shin title: Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples date: 2019-09-27 words: 9233.0 sentences: 505.0 pages: flesch: 39.0 cache: ./cache/cord-256838-8rzibpbl.txt txt: ./txt/cord-256838-8rzibpbl.txt summary: There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Several factors may affect the molecular mechanisms and subsequent clinical effects of TCM formulas, including individual gene-based response, composition and amount of active molecules in TCM formulas, complex interactions, and appropriateness of use of TCM formulas. From the viewpoint of pathophysiology, TCM formulas used to manage airway viral infections need to have antiviral activity against such viruses listed above, and/or to induce antiviral cytokines, and/or anti-inflammatory effect, and/or to relieve symptoms commonly presented in airway infections ( Figure 1 ). To simplify the molecular mechanisms and to correlate the pharmacologic activities with their clinical effects, five formulas of A-physicians will be used as examples against airway infections: Several health benefits of herbal medicine and TCM are claimed; for example, herbs and TCM formulas, including those discussed above, are believed to have anti-oxidative activities helpful against several diseases. abstract: Herbal medicine, including traditional Chinese medicine (TCM), is widely used worldwide. Herbs and TCM formulas contain numerous active molecules. Basically, they are a kind of cocktail therapy. Herb-drug, herb-food, herb-herb, herb-microbiome, and herb-disease interactions are complex. There is potential for both benefit and harm, so only after understanding more of their mechanisms and clinical effects can herbal medicine and TCM be helpful to users. Many pharmacologic studies have been performed to unravel the molecular mechanisms; however, basic and clinical studies of good validity are still not enough to translate experimental results into clinical understanding and to provide tough evidence for better use of herbal medicines. There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Understanding study validation, pharmacologic effects, drug interactions, indications and clinical effects, adverse effects and limitations, can all help clinicians in providing adequate suggestions to patients. At present, it would be better to use herbs and TCM formulas according to their traditional indications matching the disease pathophysiology and their molecular mechanisms. To unravel the molecular mechanisms and understand the benefits and harms of herbal medicine and TCM, there is still much work to be done. url: https://doi.org/10.3390/molecules24193505 doi: 10.3390/molecules24193505 id: cord-270414-gh9agf4x author: Fischer, Y. title: Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis date: 2011-10-12 words: 4579.0 sentences: 278.0 pages: flesch: 54.0 cache: ./cache/cord-270414-gh9agf4x.txt txt: ./txt/cord-270414-gh9agf4x.txt summary: title: Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis Several case reports can be found in the online Veterinary Information Network (http://www.VIN.com) that describe a positive effect of the methylxanthine derivative pentoxifylline (PTX) (Trental a ) on the survival time in cats with FIP. ALT alanine aminotransferase AP alkaline phosphatase CI confidence interval FCoV feline coronavirus FeLV feline leukemia virus FIP feline infectious peritonitis FIPV feline infectious peritonitis virus FIV feline immundeficiency virus IFAT immunofluorescent antibody technique PPF propentofylline PTX pentoxifylline RBC red blood cells SPSS statistical package for the social sciences TNF-a tumor necrosis factor-alpha TP total protein WBC white blood cells which cause endothelial cell damage. The aim of this study was to evaluate the efficacy of PPF on the survival time and quality of life in cats with a confirmed diagnosis of FIP in a placebocontrolled double-blind trial. abstract: BACKGROUND: Currently there is no drug proven to effectively treat cats with feline infectious peritonitis (FIP). HYPOTHESIS: Propentofylline (PPF) can decrease vasculitis, and therefore prolong survival time in cats with FIP, and increase their quality of life. ANIMALS: Twenty‐three privately owned cats with FIP. METHODS: Placebo‐controlled double‐blind trial. FIP was confirmed by histology or immunostaining of feline coronavirus (FCoV) antigen in effusion or tissue macrophages or both. The cats were randomly selected for treatment with either PPF or placebo. All cats received additional treatment with glucocorticoids, antibiotics, and low molecular weight heparin according to methods. RESULTS: There was no statistically significant difference in the survival time of cats treated with PPF (8 days, 95% CI 5.4–10.6) versus placebo (7.5 days, 95% CI 4.4–9.6). The median survival time of all cats was 8 days (4–36 days). There was neither a difference in quality of life (day 7, P = .892), in the amount of effusion (day 7, P = .710), the tumor necrosis factor‐alpha (TNF‐α) concentration (day 7, P = .355), nor in any other variable investigated in this study, including a complete blood count, and a small animal biochemistry profile. CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not detect an effect of PPF on the survival time, the quality of life, or any clinical or laboratory parameter in cats with FIP. Therefore, PPF does not appear to be an effective treatment option in cats with a late stage of the disease FIP. url: https://doi.org/10.1111/j.1939-1676.2011.00806.x doi: 10.1111/j.1939-1676.2011.00806.x id: cord-016523-pznw2ciu author: Fouqué, Amélie title: The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date: 2014-08-29 words: 8777.0 sentences: 427.0 pages: flesch: 41.0 cache: ./cache/cord-016523-pznw2ciu.txt txt: ./txt/cord-016523-pznw2ciu.txt summary: During interactions with respective ligands, members of the death receptor superfamily recruit adaptor proteins such as Fas-associating protein with a death domain (FADD) [ 7 , 8 ] or tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) [ 9 ] , resulting in the aggregation and activation of the initiator caspase-8 and caspase-10 to form the death-inducing signaling complex (DISC) [ 10 ] . These type I transmembrane proteins share common features, such as extracellular amino-terminal cysteine-rich domains (CRDs) [ 19 , 20 ] , which contribute to ligand specifi city [ 21 ] , and preassociation of the receptor at the plasma membrane [ 22 -24 ] and a conserved 80 amino acid sequence located in their cytoplasmic tail called death domain (DD), which is necessary for DISC formation and initiation of the apoptotic signal [ 25 , 26 ] . abstract: Apoptosis is a fundamental process contributing to tissue homeostasis, immune response, and development. CD95, also called Fas, is a member of the tumor necrosis factor receptor (TNF-R) superfamily. Its ligand, CD95L, was initially detected at the plasma membrane of activated T lymphocytes and natural killer (NK) cells where it contributes to the elimination of transformed and infected cells. Given its implication in immune homeostasis and immune surveillance combined with the fact that various lineages of malignant cells exhibit loss-of-function mutations, CD95 was initially classified as a tumor suppressor gene. Nonetheless, in different pathophysiological contexts, this receptor is able to transmit non-apoptotic signals and promote inflammation and carcinogenesis. Although the different non-apoptotic signaling pathways (NF-κB, MAPK, and PI3K) triggered by CD95 are known, the initial molecular events leading to these signals, the mechanisms by which the receptor switches from an apoptotic function to an inflammatory role, and, more importantly, the biological functions of these signals remain elusive. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120825/ doi: 10.1007/978-3-662-44006-3_9 id: cord-017640-i8h48ny6 author: Fouqué, Amélie title: The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date: 2020-01-03 words: 8811.0 sentences: 419.0 pages: flesch: 39.0 cache: ./cache/cord-017640-i8h48ny6.txt txt: ./txt/cord-017640-i8h48ny6.txt summary: The intrinsic pathway stems from accumulation of DNA damage, deregulation of mitochondrial function, or virus infection and induces the release of proapoptotic factors from the mitochondria, whereas extrinsic signals are transmitted by the binding of apoptotic ligands to death receptors present at the cell surface. During interactions with respective ligands, members of the death receptor superfamily recruit adaptor proteins such as Fas-associated protein with a death domain (FADD) [7, 8] or tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) [9] , resulting in the aggregation and activation of the initiators caspase-8 and caspase-10 to form the death-inducing signaling complex (DISC) [10] . These type I transmembrane proteins share common features, such as extracellular amino-terminal cysteine-rich domains (CRDs) [19, 20] , which contribute to ligand specificity [21] , and pre-association of the receptor at the plasma membrane [22] [23] [24] and a conserved 80-amino acid sequence located in their cytoplasmic tail called death domain (DD), which is necessary for DISC formation and initiation of the apoptotic signal [25, 26] . abstract: Apoptosis is a fundamental process contributing to tissue homeostasis, immune response, and development. CD95, also called Fas, is a member of the tumor necrosis factor receptor (TNFR) superfamily. Its ligand, CD95L, was initially detected at the plasma membrane of activated T-lymphocytes and natural killer (NK) cells where it contributes to the elimination of transformed and infected cells. Given its implication in immune homeostasis and immune surveillance combined with the fact that various lineages of malignant cells exhibit loss-of-function mutations, CD95 was initially classified as a tumor suppressor gene. Nonetheless, in different pathophysiological contexts, this receptor is able to transmit non-apoptotic signals and promote inflammation and carcinogenesis. Although the different non-apoptotic signaling pathways (NF-κB, MAPK, and PI3K) triggered by CD95 are known, the initial molecular events leading to these signals, the mechanisms by which the receptor switches from an apoptotic function to an inflammatory role, and, more importantly, the biological functions of these signals remain elusive. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122270/ doi: 10.1007/978-3-030-30845-2_11 id: cord-002119-kl431ev6 author: Garcia, Elisa title: Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury date: 2016-06-23 words: 13445.0 sentences: 687.0 pages: flesch: 41.0 cache: ./cache/cord-002119-kl431ev6.txt txt: ./txt/cord-002119-kl431ev6.txt summary: Specific inflammatory cytokines such as TNF , IL-1, and IL-6 are synthetized by various cells in the CNS and are known as mediators of the peripheral immune response 8 [118, 192] IL-4 (i) High levels 24 h AI, concentrations remain during 7 days and decrease 3 days AI (i) Neuroinflammatory regulation in various pathological conditions (ii) Confers regenerative properties to macrophages (iii) Controls free radical production in peripheral macrophages and microglia [166, [193] [194] [195] [196] [197] [198] [199] IL-13 (i) Detected 1 day AI (i) Macrophage activation onto M2 phenotype [166, 199] IP-10/CXCL10 (i) Expressed locally 30 [200, [205] [206] [207] Mediators of Inflammation 9 [200, [205] [206] [207] MCP1/CCL2 (i) Detected from 1 h AI with PL at 24 h and remains low up to 24 days AI (i) Macrophage and PMN infiltration mediator [106, 184, 200, 205, 206] min: minutes; AI: after injury; PL: peak levels. abstract: Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935915/ doi: 10.1155/2016/9476020 id: cord-295745-iw3ftw3h author: Gershoni, Jonathan M title: Molecular decoys: antidotes, therapeutics and immunomodulators date: 2008-11-18 words: 5546.0 sentences: 276.0 pages: flesch: 42.0 cache: ./cache/cord-295745-iw3ftw3h.txt txt: ./txt/cord-295745-iw3ftw3h.txt summary: Decoys not only provide the means to fine tune the regulation of these phenomena; they also serve as potential leads for the development of recombinant anti-toxins, anti-viral agents and novel therapeutics for combating cancer and inflammatory disease. For almost every membrane receptor of cytokines, growth factors and cell adhesins, soluble versions were found to be naturally produced by cells; hence ''natural decoys'' that function as modifiers of the potent stimulants and regulators of inflammation and immune response. Telovamer, a soluble, high molecular weight anionic polymer represents a ''functional decoy'' able to bind and neutralize both Toxin A and Toxin B of Clostridium difficile yet is not derived from the natural receptor for these toxins. Nature produces such soluble receptors in order to crucially regulate immune responses towards cancer and infection as well as inflammation in general (Figure 1 ). This is particularly relevant for chemokine receptors whose decoys persist as membrane proteins that are effective in ligand binding but ''handicapped'' in signal transduction. abstract: Receptor–ligand interactions are fundamental to the regulation of cell physiology, enabling the communication between cells and their environment via signal transduction. Receptors are also exploited by toxins and infectious agents to mediate pathogenesis. Over the past 20 years, however, this bi-partite paradigm for cellular regulation, that is, receptors and their ligands, has been revised to include an unforeseen participant namely, soluble receptors or molecular decoys. Decoys function as nature's modifiers of potent responses such as inflammation, stimulation of cell proliferation and triggering apoptosis. Decoys not only provide the means to fine tune the regulation of these phenomena; they also serve as potential leads for the development of recombinant anti-toxins, anti-viral agents and novel therapeutics for combating cancer and inflammatory disease. url: https://www.ncbi.nlm.nih.gov/pubmed/18977299/ doi: 10.1016/j.copbio.2008.10.001 id: cord-278339-6ddsj014 author: Gianfrancesco, Milena title: Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry date: 2020-05-29 words: 5376.0 sentences: 298.0 pages: flesch: 41.0 cache: ./cache/cord-278339-6ddsj014.txt txt: ./txt/cord-278339-6ddsj014.txt summary: The independent associations between demographic and disease-specific features with the odds of COVID-19 hospitalisation were estimated using multivariable-adjusted logistic regression and reported as OR and 95% CIs; covariates included in the model were age group (<65 years vs >65 years), sex, rheumatic disease (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) or other spondyloarthritis, vasculitis and other), key comorbidities (hypertension, lung disease, diabetes, cardiovascular disease and chronic renal insufficiency/end-stage renal disease), smoking status (ever vs never), physician-reported disease activity (remission, minimal/low disease activity, moderate disease activity or severe/high disease activity; or as a binary variable: remission and minimal/low disease activity vs moderate and severe/high disease activity), DMARD type (no DMARD, csDMARD only, b/tsDMARD only, csDMARD and b/tsDMARD combination therapy), non-steroidal anti-inflammatory drugs (NSAID) use (yes vs no) and prednisone-equivalent glucocorticoid use (0 mg/ day, 1-9 mg/day, ≥10 mg/day). abstract: OBJECTIVES: COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. METHODS: Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. RESULTS: A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. CONCLUSIONS: We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation. url: https://doi.org/10.1136/annrheumdis-2020-217871 doi: 10.1136/annrheumdis-2020-217871 id: cord-275730-650sjwyy author: Gogoi, Himanshu title: The Age of Cyclic Dinucleotide Vaccine Adjuvants date: 2020-08-13 words: 8347.0 sentences: 519.0 pages: flesch: 50.0 cache: ./cache/cord-275730-650sjwyy.txt txt: ./txt/cord-275730-650sjwyy.txt summary: As therapeutic cancer vaccine adjuvants, CDNs induce potent anti-tumor immunity, including cytotoxic T cells and NK cells activation that achieve durable regression in multiple mouse models of tumors. (STINGel) Synthetic ML-RpRp-SS-CDA in multidomain peptide hydrogel (s.c.) [60] Slow-release of CDN and highly effective in maintaining tumor clearance and rejecting tumor growth and provide durable anti-tumor immunity CDG in YSK05 liposome (s.c.) [61] Activation of antigen-specific CTL activity and restrict murine tumor growth completely ADU-S100 (Synthetic ML-RpRp-SS-CDA) in combination with anti-PD1 or anti-CTLA4 antibody (intratumoral) [62] Low-dosage promotes local STING activation primarily in monocytic cell lineages whereas a high-dose resulted in cellular activation at distal sites A combination of ADU-S100 and α-CPI provide durable immunity even against cold tumors Synthetic RpRp-SS-CDG and ML-RpRp-CDA in PBAE nanoparticles and anti-PD1 antibody (intratumoral) [56] Enhanced shelf-life stability for up to nine months. abstract: As prophylactic vaccine adjuvants for infectious diseases, cyclic dinucleotides (CDNs) induce safe, potent, long-lasting humoral and cellular memory responses in the systemic and mucosal compartments. As therapeutic cancer vaccine adjuvants, CDNs induce potent anti-tumor immunity, including cytotoxic T cells and NK cells activation that achieve durable regression in multiple mouse models of tumors. Clinical trials are ongoing to fulfill the promise of CDNs (ClinicalTrials.gov: NCT02675439, NCT03010176, NCT03172936, and NCT03937141). However, in October 2018, the first clinical data with Merck’s CDN MK-1454 showed zero activity as a monotherapy in patients with solid tumors or lymphomas (NCT03010176). Lately, the clinical trial from Aduro’s CDN ADU-S100 monotherapy was also disappointing (NCT03172936). The emerging hurdle in CDN vaccine development calls for a timely re-evaluation of our understanding on CDN vaccine adjuvants. Here, we review the status of CDN vaccine adjuvant research, including their superior adjuvant activities, in vivo mode of action, and confounding factors that affect their efficacy in humans. Lastly, we discuss the strategies to overcome the hurdle and advance promising CDN adjuvants in humans. url: https://www.ncbi.nlm.nih.gov/pubmed/32823563/ doi: 10.3390/vaccines8030453 id: cord-295683-eoxxal8v author: Gong, R. title: Hepatocyte growth factor suppresses acute renal inflammation by inhibition of endothelial E-selectin date: 2006-04-01 words: 4481.0 sentences: 266.0 pages: flesch: 42.0 cache: ./cache/cord-295683-eoxxal8v.txt txt: ./txt/cord-295683-eoxxal8v.txt summary: This study examined the effect of HGF on endothelial E-selectin expression in acute inflammation induced by tumor necrosis factor (TNF)-α. In vitro, HGF suppressed TNF-α-induced cell surface expression of E-selectin in human umbilical vein endothelial cells (HUVEC) and inhibited E-selectin mediated monocytic adhesion to endothelial monolayers. In addition, selective inhibition of GSK3 activity by lithium suppressed TNF-α-induced E-selectin expression and monocytic adhesion, reminiscent of the action of HGF. [6] [7] [8] [9] [10] In the present study, we found that HGF suppresses monocyte to endothelial adhesion and attenuates acute renal inflammation via inhibition of endothelial E-selectin expression. In our study, HGF was found to suppress endothelial E-selectin expression in cultured HUVEC cells and in vivo in rats injected with TNF-a. In summary, HGF suppresses E-selectin expression in the activated endothelium and thereby attenuates monocyte to endothelial adhesion and alleviates acute inflammation in the kidney. abstract: Vascular endothelial activation, marked by de novo expression of E-selectin, is an early and essential event in the process of leukocyte extravasation and inflammation. Evidence suggests that hepatocyte growth factor (HGF) ameliorates inflammation in animal models of renal disease, implying that HGF might inhibit specific components of the inflammatory response. This study examined the effect of HGF on endothelial E-selectin expression in acute inflammation induced by tumor necrosis factor (TNF)-α. In vitro, HGF suppressed TNF-α-induced cell surface expression of E-selectin in human umbilical vein endothelial cells (HUVEC) and inhibited E-selectin mediated monocytic adhesion to endothelial monolayers. HGF activated phosphatidylinositol 3-kinase (PI3K)–Akt that in turn inhibited its downstream transducer glycogen synthase kinase (GSK)3. Blockade of the PI3K–Akt pathway with specific inhibitors abrogated HGF induced inhibitory phosphorylation of GSK3 and suppression of E-selectin. In addition, selective inhibition of GSK3 activity by lithium suppressed TNF-α-induced E-selectin expression and monocytic adhesion, reminiscent of the action of HGF. Moreover, ectopic expression of an uninhibitable mutant GSK3β, in which the regulatory serine-9 is replaced by alanine, abolished HGF's suppressive effect on endothelial E-selectin. In vivo, administration of exogenous HGF reduced endothelial expression of E-selectin induced by bolus injection of TNF-α. This was associated with less sequestration of circulating fluorescence-labeled macrophages in the kidney. These findings suggest that HGF ameliorates acute renal inflammation in part by downregulating E-selectin mediated macrophage adhesion to the inflamed endothelium. url: https://www.sciencedirect.com/science/article/pii/S0085253815516505 doi: 10.1038/sj.ki.5000246 id: cord-354765-abayh871 author: Graham, R. S. title: Calming the Cytokine Storm - Splenic Ultrasound for Treating Inflammatory Disorders and Potentially COVID-19 date: 2020-07-17 words: 8835.0 sentences: 400.0 pages: flesch: 42.0 cache: ./cache/cord-354765-abayh871.txt txt: ./txt/cord-354765-abayh871.txt summary: Here, we show results from the first in-human trials using non-invasive ultrasound stimulation of the spleen to reduce cytokine release in the context of both an acute response in healthy subjects and a chronic inflammatory condition in rheumatoid arthritis patients. In RA patients, we observed that daily splenic ultrasound stimulation results in reduction of blood-borne transcripts encoding for pro-inflammatory markers IL-1β, IL-8, and NFκB, as well as suppresses pathways involved in IL-6 and TNF production. Our additional pre-clinical animal data further demonstrates that in addition to dampening cytokine output and circulating monocyte invasiveness, prophylactic ultrasound activation of the splenic neuroimmune pathway results in enhanced antibody response upon exposure to an inflammatory antigen. By presenting the first in-human data from two independent studies using different devices and protocols, we have consistently demonstrated that non-invasive ultrasound stimulation of the spleen drives anti-inflammatory effects in the context of both an acute response in healthy subjects and a chronic inflammatory condition. abstract: Hyperinflammation and uncontrolled cytokine release, which can be seen in severe cases of COVID-19, require therapy to reduce the innate immune response without hindering necessary adaptive immune mechanisms. Here, we show results from the first in-human trials using non-invasive ultrasound stimulation of the spleen to reduce cytokine release in the context of both an acute response in healthy subjects and a chronic inflammatory condition in rheumatoid arthritis patients. Splenic ultrasound results in a reduction in TNF serum levels, as well as IL-1B; and IL-8 transcript levels in monocytes. There is also a down regulation of pathways involved in TNF and IL-6 production, and IFNgamma- and NFKB-regulated genes. Many of these cytokines or pathways are upregulated in COVID-19 patients. There is also a reduction in chemokine transcript levels and other components of the chemotactic response, suggesting that reduction of cellular migration may contribute to the therapeutic effects of ultrasound. There is no inhibition of the adaptive immune response with ultrasound treatment relating to antibody production. This is consistent with a pre-clinical animal model where enhanced antibody production was achieved with splenic ultrasound. Therefore, this new splenic ultrasound approach has the potential to treat acute and chronic hyper-inflammatory diseases, as it lowers cytokine levels without disrupting the normal adaptive immune response. Portable ultrasound technologies are currently being developed and translated to the clinic to treat various inflammatory disorders, with more recent efforts directed towards combatting the hyperinflammation or cytokine storm in COVID-19 patients. url: http://medrxiv.org/cgi/content/short/2020.07.14.20153528v1?rss=1 doi: 10.1101/2020.07.14.20153528 id: cord-015910-d9gxew91 author: Grimble, Robert F. title: The Interaction Between Nutrition and Inflammatory Stress Throughout the Life Cycle date: 2005 words: 15205.0 sentences: 709.0 pages: flesch: 40.0 cache: ./cache/cord-015910-d9gxew91.txt txt: ./txt/cord-015910-d9gxew91.txt summary: Binding of the transcription factors is implicated in activation of a wide range of genes associated with inflammation and the immune response, including those encoding cytokines, cytokine receptors, cell adhesion molecules, acute-phase proteins, and growth factors (Schreck, Rieber, & Baeurerle, 1991) (Fig. 4 ) . While inflammation may be exerting deleterious effects most obviously in patients, people on the borderline of health and disease living in the general population Table 4 Nutrients Commonly Used in Immunonutrient Supplements and Their Potential Mode of Action • n-3 polyunsaturated fatty acids: act as anti-inflammatory agents and reverse immunosuppression • Sulfur amino acids and their precursors: enhance antioxidant status via GSH synthesis • Glutamine: nutrient for immune cells, improves gut barrier function, precursor for GSH • Arginine: stimulates nitric oxide and growth hormone production, improves helper T-cell numbers • Nucleotides: RNA and DNA precursors, improve T-cell function may also require nutritional modulation of ongoing inflammatory processes. abstract: The human race inhabits a world in which it is surrounded by a myriad of different microorganisms—yeasts, bacteria, protozoa, and viruses. Most of these are benign, and some, such as the normal gut flora, play an important part in promoting health via the synthesis of vitamins and stimulation of normal function of gut epithelia. Approximately 0.1% of microbes in our environment have catastrophic effects if they penetrate the epithelial surfaces of the body (Bryson, 2003). History reveals many instances in which armies have been defeated and civilizations have collapsed because of encounters between humans and such microorganisms (Diamond, 1999). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120013/ doi: 10.1385/1-59259-952-4:387 id: cord-017309-pt27efu1 author: Gupta, G. S. title: Selectins and Associated Adhesion Proteins in Inflammatory disorders date: 2012-03-20 words: 25423.0 sentences: 1303.0 pages: flesch: 40.0 cache: ./cache/cord-017309-pt27efu1.txt txt: ./txt/cord-017309-pt27efu1.txt summary: Activation of endothelial cells (EC) with different stimuli induces the expression of E-and P-selectins, and other adhesion molecules (ICAM-1, VCAM-1), involved in their interaction with circulating cells. Accordingly, population studies have explored the association of ischaemic heart disease with gene polymorphisms of the inflammatory molecules: tumor necrosis factors (TNF) a and b, transforming growth factors (TGF) b1 and 2, P and E selectins, and platelet endothelial cell adhesion molecule (PECAM) 1. Endothelial dysfunction in type 2 diabetic patients is associated with inflammation, increased levels of circulating soluble adhesion molecules (VCAM-1 and E-selectin), and inducing production of ROS, and urinary albumin excretion (Potenza et al. The A 561 C polymorphism of E-selectin gene may be associated with disease progression in patients with chronic HBV infection and control the expression of plasma soluble levels, while the G 98 T polymorphism may be related to fibrotic severity in Chinese population (Wu et al. abstract: Inflammation is defined as the normal response of living tissue to injury or infection. It is important to emphasize two components of this definition. First, that inflammation is a normal response and, as such, is expected to occur when tissue is damaged. Infact, if injured tissue does not exhibit signs of inflammation this would be considered abnormal and wounds and infections would never heal without inflammation. Secondly, inflammation occurs in living tissue, hence there is need for an adequate blood supply to the tissues in order to exhibit an inflammatory response. The inflammatory response may be triggered by mechanical injury, chemical toxins, and invasion by microorganisms, and hypersensitivity reactions. Three major events occur during the inflammatory response: the blood supply to the affected area is increased substantially, capillary permeability is increased, and leucocytes migrate from the capillary vessels into the surrounding interstitial spaces to the site of inflammation or injury. The inflammatory response represents a complex biological and biochemical process involving cells of the immune system and a plethora of biological mediators. Cell-to-cell communication molecules such as cytokines play an extremely important role in mediating the process of inflammation. Inflammation and platelet activation are critical phenomena in the setting of acute coronary syndromes. An extensive exposition of this complex phenomenon is beyond the scope of this article (Rankin 2004). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121831/ doi: 10.1007/978-3-7091-1065-2_44 id: cord-282242-5tkhjiwl author: Gómez-Laguna, J. title: Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus date: 2009-08-19 words: 3816.0 sentences: 206.0 pages: flesch: 49.0 cache: ./cache/cord-282242-5tkhjiwl.txt txt: ./txt/cord-282242-5tkhjiwl.txt summary: title: Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Several studies have examined the role of cytokines in the pathogenesis of PRRS (Van Reeth and Nauwynck, 2000) ; however, it is not clear how cytokines participate in macrophage activation during PRRSV infection or how they regulate development of the immune response to the virus. The expression of IFN-g by macrophages and lymphocytes has been previously reported in the lung of PRRSV-infected pigs (Thanawongnuwech et al., 2003) . Therefore, the expression of IL-10 observed in the present study might be responsible for reduced expression of cytokines such as IFN-a, IFN-g, IL-12p40 and TNF-a, that in turn may impair prolonged viral replication in the lung of infected animals. abstract: Porcine reproductive and respiratory syndrome (PRRS) is caused by a virus that predominantly replicates in alveolar macrophages. The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Expression of interleukin (IL) 1α, IL-6 and tumour necrosis factor (TNF)-α correlated with the severity of pulmonary pathology and the numbers of pulmonary macrophages. Significant correlations were observed between PRRSV infection and the expression of IL-10, between the expression of IL-12p40 and interferon (IFN)-γ, and between the expression of TNF-α and IFN-γ. These findings suggest that PRRSV modulates the immune response by the up-regulation of IL-10, which may in turn reduce expression of cytokines involved in viral clearance (e.g. IFN-α, IFN-γ, IL-12p40 and TNF-α). The results also suggest that expression of IFN-γ is stimulated by IL-12p40 and TNF-α, but not by IFN-α. All of these cytokines were expressed mainly by septal macrophages with weaker expression by alveolar macrophages, lymphocytes and neutrophils. There appears to be differential activation of septal and alveolar macrophages in PRRSV infection, with septal macrophages being the major source of cytokines. url: https://doi.org/10.1016/j.jcpa.2009.07.004 doi: 10.1016/j.jcpa.2009.07.004 id: cord-023392-axd0901z author: Hansen, T. K. title: Association between Mannose‐Binding Lectin and Vascular Complications in Type 1 Diabetes date: 2008-06-28 words: 16944.0 sentences: 875.0 pages: flesch: 46.0 cache: ./cache/cord-023392-axd0901z.txt txt: ./txt/cord-023392-axd0901z.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Complement activation and inflammation have been suggested in the pathogenesis of diabetic vascular lesions. We investigated serum mannose‐binding lectin (MBL) levels and polymorphisms in the MBL gene in type 1 diabetic (T1DM) patients with and without diabetic nephropathy and associated macrovascular complications. Polymorphisms in the MBL gene and serum MBL levels were determined in 199 T1DM patients with overt nephropathy and 192 T1DM patients with persistent normoalbuminuria matched for age, sex and duration of diabetes as well as in 100 healthy control subjects. The frequencies of high and low expression MBL genotypes were similar in patients with T1DM and healthy controls. High MBL genotypes were significantly more frequent in diabetic patients with nephropathy than in the normoalbuminuric group, and the risk of having nephropathy, given a high MBL genotype, assessed by odds ratio was 1.52 (1.02–2.27), P = 0.04. Median serum MBL concentrations were significantly higher in patients with nephropathy than in patients with normoalbuminuria [2306 µg/l (IQR 753–4867 µg/l) versus 1491 µg/l (IQR 577–2944), P = 0.0003], and even when comparing patients with identical genotypes, serum MBL levels were higher in the nephropathy group than in the normoalbuminuric group. Patients with a history of cardiovascular disease had significantly elevated MBL levels independently of nephropathy status [3178 µg/l (IQR 636–5231 µg/l) versus 1741 µg/l (IQR 656–3149 µg/l), P = 0.02]. The differences in MBL levels between patients with and without vascular complications were driven primarily by pronounced differences among carriers of high MBL genotypes (P < 0.0001). Our findings suggest that MBL may be involved in the pathogenesis of microvascular and macrovascular complications in type 1 diabetes and that determination of MBL status might be used to identify patients at increased risk of developing these complications. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169517/ doi: 10.1111/j.0300-9475.2004.01423i.x id: cord-344204-qq2vqzc2 author: Hariharan, Apurva title: The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients date: 2020-11-07 words: 5647.0 sentences: 307.0 pages: flesch: 47.0 cache: ./cache/cord-344204-qq2vqzc2.txt txt: ./txt/cord-344204-qq2vqzc2.txt summary: Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a "cytokine storm" causing inflammatory response and destruction, mainly affecting the lungs. Immunomodulation at the level of NF-κB activation and inhibitors of NF-κB (IκB) degradation along with TNF-α inhibition will potentially result in a reduction in the cytokine storm and alleviate the severity of COVID-19. During previous coronavirus outbreaks, such as SARS-CoV and the Middle East Respiratory syndrome coronavirus (MERS-CoV) , it was reported that viral proteins such as nsp1, nsp3a, nsp7a, spike, and nucleocapsid protein all caused excessive NF-κB activation, possibly contributing to severe disease and high case-fatality rate (DeDiego et al. Herein, we review current literature on the effect of SARS-nCoV-2 infection on NF-κB activation and discuss the potential therapeutic role of inhibitors of this pathway in the treatment of COVID-19. abstract: Coronavirus disease 2019 (COVID-19) pandemic has affected health care systems worldwide. Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a “cytokine storm” causing inflammatory response and destruction, mainly affecting the lungs. COVID-19 activation of transcription factor, NF-kappa B (NF-κB) in various cells such as macrophages of lung, liver, kidney, central nervous system, gastrointestinal system and cardiovascular system leads to production of IL-1, IL-2, IL-6, IL-12, TNF-α, LT-α, LT-β, GM-CSF, and various chemokines. The sensitised NF-κB in elderly and in patients with metabolic syndrome makes this set of population susceptible to COVID-19 and their worse complications, including higher mortality. Immunomodulation at the level of NF-κB activation and inhibitors of NF-κB (IκB) degradation along with TNF-α inhibition will potentially result in a reduction in the cytokine storm and alleviate the severity of COVID-19. Inhibition of NF-κB pathway has a potential therapeutic role in alleviating the severe form of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33159646/ doi: 10.1007/s10787-020-00773-9 id: cord-001039-qocuprwb author: Hayasaka, Daisuke title: TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection date: 2013-08-05 words: 8562.0 sentences: 464.0 pages: flesch: 51.0 cache: ./cache/cord-001039-qocuprwb.txt txt: ./txt/cord-001039-qocuprwb.txt summary: We next compared severe or mild cases of mice infected with JEV exhibiting doseindependent mortality and investigated the specific host responses such as TNF-α and IL-10 expression in the CNS. Corresponding to the viral loads, histopathological examination showed that a large number of neurons displayed JEV antigens and severe cuffing was observed in the brain cortex of JaTH160-infected mice at 9 day pi ( Figure 1F ). Following inoculation with JaOArS982 virus, there were no significant differences of infectious viral loads in the brain cortex between WT, IL-10 KO and TNF-α KO at 5, 9 and 11 days pi ( Figure 5B ). TNF-α KO mice exhibited significantly increased levels of IFN-γ and IL-5 in the brains compared with WT and/or IL-10 KO mice at 5 and 7 days pi following JaTH160 inoculation ( Figure 7C and D) . abstract: Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis. However, the mechanism of severe encephalitis has not been fully elucidated. In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection. Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome. Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases. However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection. Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice. However, exaggerated inflammatory responses were observed in the CNS of TNF-α KO mice. Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice. Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease. Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease. In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733918/ doi: 10.1371/journal.pone.0071643 id: cord-322250-7kjakuyw author: He, Jia title: Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice date: 2020-07-02 words: 4895.0 sentences: 285.0 pages: flesch: 46.0 cache: ./cache/cord-322250-7kjakuyw.txt txt: ./txt/cord-322250-7kjakuyw.txt summary: title: Anemoside B4 protects against Klebsiella pneumoniaeand influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)and influenza virus FM1 (FM1)-induced pneumonia mice model. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, significant increase was observed in the TNF-α (Fig. 3d, g) , IL-6 ( Fig. 3e, h) , IL-1β (Fig. 3f ) , and MPO (Fig. 3i) in the BALF and lung tissue samples collected from the KP-infected pneumonia mice, which were reversed by anemoside B4. Influenza virus FM1-infected pneumonia leads to an inflammatory storm, suggesting that many pro-inflammatory cytokines like TNF-α and IL-6 released into blood and lung tissue [28] [29] [30] . abstract: BACKGROUND: Pneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model. METHODS: The network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP-induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (ribavirin or ceftriaxone sodium injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin staining (HE) staining. Proteins expression was quantified by western blotting. RESULTS: The network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway. CONCLUSION: Our findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia. url: https://doi.org/10.1186/s13020-020-00350-w doi: 10.1186/s13020-020-00350-w id: cord-023439-r04y1j22 author: Hedegaard, C. J. title: The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4(+) T‐cell Responses to MBP in Health and Multiple Sclerosis date: 2008-06-28 words: 16932.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023439-r04y1j22.txt txt: ./txt/cord-023439-r04y1j22.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. abstract: Multiple sclerosis (MS) is an autoimmune condition characterized by degeneration of nerve fibre myelin sheets. A candidate autoantigen, myelin basic protein (MBP), has especially attracted attention. The presence of anti‐MBP antibodies is a predictor of definite MS, but their role in the pathogenesis remains obscure. T cells have long been known to play a pivotal role in the pathogenesis of MS. Recently, an important role for B cells as autoantigen‐presenting cells has been demonstrated in other autoimmune diseases, including rheumatoid arthritis and diabetes. The uptake of MBP by B cells and the presentation of MBP‐derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease‐associated anti‐MBP antibodies in MS patients, respectively. We have investigated the formation of MBP‐containing IC, the binding of MBP to B cells, the MBP‐elicited induction of Th‐cell and B‐cell proliferation and the cytokine production in peripheral blood mononuclear cells (PBMCs) from healthy donors grown in the presence of intact or C‐inactivated serum from healthy donors or patients with MS. While MBP did not induce measurable proliferation of B cells nor CD4(+) T cells, we observed the production of TNF‐α, IFN‐γ and IL‐10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. By contrast, no production of IL‐2, IL‐4 and IL‐5 was detected. We are currently investigating the capability of MS sera to promote the formation of MBP‐containing IC and thereby enhance the cytokine responses, by virtue of elevated anti‐MBP contents. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169603/ doi: 10.1111/j.0300-9475.2004.01423k.x id: cord-347298-7kqrl3rv author: Hedger, M.P. title: Immunology of the Testis and Male Reproductive Tract date: 2010-07-12 words: 21168.0 sentences: 1000.0 pages: flesch: 46.0 cache: ./cache/cord-347298-7kqrl3rv.txt txt: ./txt/cord-347298-7kqrl3rv.txt summary: Thus, it appears unlikely that a lack of APCs is a contributing factor in testicular immune privilege, although differences in the number and distribution of MHC class II-expressing cells in the interstitial tissue of different species or strains may help to explain differences in susceptibility to autoimmune orchitis (Flickinger et al. Moreover, while inhibition of Leydig cell steroidogenesis during inflammation may involve indirect effects at the level of the pituitary, or the actions of inflammatory mediators produced by the testicular macrophages and Sertoli cells, there is evidence that these cells can also respond directly to TLR ligands (Bhushan et al. Activation of p38/Jnk is implicated in the stimulation of proliferation by immature Sertoli cells and the regulation of blood-testis barrier dynamics, steroidogenesis, and multiple inflammatory responses, including the production of IL6, iNOS, monocyte chemoattractant protein 1, and leukocyte adhesion molecules, in the mature Sertoli cell (De Cesaris et al. abstract: A large body of evidence points to the existence of a close, dynamic relationship between the immune system and the male reproductive tract, which has important implications for our understanding of both systems. The testis and the male reproductive tract provide an environment that protects the otherwise highly immunogenic spermatogenic cells and sperm from immunological attack. At the same time, secretions of the testis, including androgens, influence the development and mature functions of the immune system. Activation of the immune system has negative effects on both androgen and sperm production, so that systemic or local infection and inflammation compromise male fertility. The mechanisms underlying these interactions have begun to receive the attention from reproductive biologists and immunologists that they deserve, but many crucial details remain to be uncovered. A complete picture of male reproductive tract function and its response to toxic agents is contingent upon continued exploration of these interactions and the mechanisms involved. url: https://api.elsevier.com/content/article/pii/B978008046884601112X doi: 10.1016/b978-0-08-046884-6.01112-x id: cord-335185-3qi29i6n author: Hendry, Bruce M. title: Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID‐19 patients date: 2020-07-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We propose a new hypothesis that the established drug pentoxifylline deserves attention as a potential repurposed therapeutic for COVID‐19. Pentoxifylline is an immunomodulator with anti‐inflammatory properties. It is a nonselective phosphodiesterase inhibitor and through Adenosine A2A Receptor‐mediated pathways reduces tumor necrosis factor alpha, interleukin 1, interleukin 6, and interferon gamma and may act to reduce tissue damage during the cytokine storm host response to SARS‐CoV‐2 infection. This agent has been used clinically for many years and has a favorable profile of safety and tolerability. Pre‐clinical data support pentoxifylline as effective in cytokine‐driven lung damage. Clinical studies of pentoxifylline in radiation and cytokine‐induced lung damage in humans are positive and consistent with anti‐inflammatory efficacy. Pentoxifylline is a readily available, off‐patent and inexpensive drug, suitable for large‐scale use including in resource‐limited countries. Current trials of therapeutics are largely focused on the inhibition of viral processes. We advocate urgent randomized trials of pentoxifylline for COVID‐19 as a complementary approach to target the host responses. url: https://www.ncbi.nlm.nih.gov/pubmed/32715661/ doi: 10.1002/prp2.631 id: cord-023388-btbf6wkg author: Hoffmann, H. J. title: Decrease in Fine T‐cell Subset ratio MT2/MT1 During Steroid Reduction of Asthmatic Patients date: 2008-06-28 words: 16918.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023388-btbf6wkg.txt txt: ./txt/cord-023388-btbf6wkg.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Combining inhaled long‐acting β‐2 agonist (LABA) and inhaled corticosteroid (ICS) seems to offer asthma control at a lower dose of ICS than achieved by ICS alone. Fine mapping of T‐cell surface markers by flow cytometry offers a detailed status of the individual's inflammatory response. The frequency of MT2 (CD4(+)CD45RA(–)CD62L(+)CD11adim) and MT1 (CD4(+)CD45RA(–)CD62L(–)CD11abright) cells in peripheral blood, and their ratio, has been shown to differ predictably in atopics and patients with leprosy, where MT2 correlates with a Th2 phenotype and MT1 with a Th1 phenotype. Stable asthmatics, requiring fluticasone propionate (FP) 750–1000 µg daily or equivalent, were randomized to receive, double‐blinded, either Seretide(®)[salmeterol and fluticasone propionate (SFC, n = 16)] 50 µg/500 µg bd or FP 500 µg bd (n = 17). If asthma was controlled based on lung function and symptoms at clinic visits every 6 weeks, ICS dose was tapered until asthma exacerbated or 0 µg was reached. The frequency and ratio of MT2 and MT1 T cells of the patients was monitored at 6 week intervals. As treatment tapered, the frequency of MT2 cells decreased (P = 0038 from first to final visit), whereas that of MT1 cells increased. The ratio of MT2/MT1 decreased (P = 0049 from first to final visit). In patients receiving LABA + ICS, the fall in MT2/MT1 ratio appeared to be more pronounced than in patients receiving ICS alone. Thus, the MT2 phenotype may be associated with stable asthma, whereas an imminent exacerbation may associate with an increase in the MT1 phenotype. LABA may allow for a greater effect of FP on the MT ratio. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169509/ doi: 10.1111/j.0300-9475.2004.01423ah.x id: cord-297128-s5c9h4lm author: Hong, Joung-Woo title: Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models date: 2012-11-28 words: 3856.0 sentences: 210.0 pages: flesch: 52.0 cache: ./cache/cord-297128-s5c9h4lm.txt txt: ./txt/cord-297128-s5c9h4lm.txt summary: title: Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. Inhibitory effect of the CWE fraction containing highmolecular-weight compounds on signaling molecules in LPS-stimulated macrophages In addition, LPS-induced IκBα degradation and MAP kinase phosphorylation in macrophages was strongly inhibited by the polyphenol-rich CWE fraction. Oral administration of CWE decreased serum levels of LPS-induced TNF-α and IL-6, but such anti-inflammatory activity was attenuated in the high dose group. The inhibitory effect of CWE on the signaling pathways mediated by NF-κB and MAP kinases occurred in its polyphenol-rich high MW fraction. CWE inhibited IκBα degradation and MAP kinase activation in LPS-stimulated macrophages in vitro. Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models abstract: BACKGROUND: Cinnamon bark is one of the most popular herbal ingredients in traditional oriental medicine and possesses diverse pharmacological activities including anti-bacterial, anti-viral, and anti-cancer properties. The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. METHODS: CWE was orally administrated to mice for 6 days prior to intraperitoneal injection of LPS. Serum levels of TNF-α and interleukin (IL)-6 were determined 1 hour after LPS stimulation. Peritoneal macrophages from thioglycollate-injected mice were isolated and assayed for viability, cytokine expression and signaling molecules upon LPS stimulation. CWE was further fractioned according to molecular size, and the levels of total polyphenols and biological activities of each fraction were measured. RESULTS: The oral administration of CWE to mice significantly decreased the serum levels of TNF-α and IL-6. CWE treatment in vitro decreased the mRNA expression of TNF-α. CWE blocked the LPS-induced degradation of IκBα as well as the activation of JNK, p38 and ERK1/2. Furthermore, size-based fractionation of CWE showed that the observed inhibitory effect of CWE in vitro occurred in the fraction containing the highest level of total polyphenols. CONCLUSIONS: Treatment with CWE decreased LPS-induced TNF-α in serum. In vitro inhibition of TNF-α gene by CWE may occur via the modulation of IκBα degradation and JNK, p38, and ERK1/2 activation. Our results also indicate that the observed anti-inflammatory action of CWE may originate from the presence of polyphenols. url: https://doi.org/10.1186/1472-6882-12-237 doi: 10.1186/1472-6882-12-237 id: cord-306577-gq6fss5l author: Hsueh, Wei title: Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts date: 2002-11-11 words: 8414.0 sentences: 453.0 pages: flesch: 40.0 cache: ./cache/cord-306577-gq6fss5l.txt txt: ./txt/cord-306577-gq6fss5l.txt summary: Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. We developed a model of bowel necrosis in adult rats and mice by injecting endotoxin (lipopolysaccharide, LPS) [32] , PAF (platelet-activating factor, paf-acether) [33, 34] , tumor necrosis factor-␣ (TNF) [35] , or a combination of these agents. Experimental evidence strongly supports the role of PAF, LPS, and TNF in acute ischemic bowel necrosis and in the neonatal rat model of NEC. Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (PAF-acether) abstract: Necrotizing enterocolitis (NEC), a disease affecting predominantly premature infants, is a leading cause of morbidity and mortality in neonatal intensive care units. Although several predisposing factors have been identified, such as prematurity, enteral feeding, and infection, its pathogenesis remains elusive. In the past 20 years, we have established several animal models of NEC in rats and found several endogenous mediators, especially platelet-activating factor (PAF), which may play a pivotal role in NEC. Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The same is true for lesions induced by hypoxia and enteral feeding in neonatal animals. Human patients with NEC show high levels of PAF and decreased plasma PAF-acetylhydrolase, the enzyme degrading PAF. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. Subsequent norepinephrine release and mesenteric vasoconstriction result in splanchnic ischemia and reperfusion. Bacterial products (e.g., endotoxin) enter the intestinal tissue during local mucosal barrier breakdown, and endotoxin synergizes with PAF to amplify the inflammation. Reactive oxygen species produced by the activated leukocytes and by intestinal epithelial xanthine oxidase may be the final pathway for tissue injury. Protective mechanisms include nitric oxide produced by the constitutive (mainly neuronal) nitric oxide synthase, and indigenous probiotics such as Bifidobacteria infantis. The former maintains intestinal perfusion and the integrity of the mucosal barrier, and the latter keep virulent bacteria in check. The development of tissue injury depends on the balance between injurious and protective mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/12424605/ doi: 10.1007/s10024-002-0602-z id: cord-023407-s85g7g0x author: Huang, Y.‐M. title: Anti‐Inflammatory Liver X Receptors and Related Molecules in Multiple Sclerosis Patients from Sardinia and Sweden date: 2008-06-28 words: 17075.0 sentences: 876.0 pages: flesch: 47.0 cache: ./cache/cord-023407-s85g7g0x.txt txt: ./txt/cord-023407-s85g7g0x.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: The nuclear receptor heterodimers of liver X receptors (LXRs) are recently identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs and their ligands are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, incidence is lower, with an exception for Sardinia where the incidence is even higher than that in Sweden. Subjects from Sardinia are ethnically more homogeneous and differ from Swedes, also regarding genetic background and environment. We studied LXRs and their related molecules of blood mononuclear cells (MNCs) from female patients with untreated relapsing‐remitting MS from Sassari, Sardinia and Stockholm, Sweden. Sex‐ and age‐matched healthy controls (HCs) were from both areas. mRNA expression was evaluated by real‐time PCR. LXR‐α was lower (P < 0.05) in MS (mean ± SEM: 3.1 ± 0.2; n = 37) compared to HC (3.6 ± 0.1; n = 37). LXR‐α was lower in MS from Stockholm (2.6 ± 0.2; n = 22) compared to corresponding HC (3.4 ± 0.1; n = 22; P < 0.01) and compared to MS (3.8 ± 0.2; n = 15; P < 0.001) and HC (4 ± 0.2; n = 15; P < 0.001) from Sardinia. MS patients from Stockholm, but not from Sassari, also expressed lower (P < 0.05) LXR‐β (−4.1 ± 0.4) compared to corresponding HC (−2.9 ± 0.3). MS from Stockholm was associated with higher ABCA‐1 (6.1 ± 0.4 versus 5.0 ± 0.3; P < 0.05) and higher estrogen receptor‐β‐Cx (2.4 ± 0.4 versus 0.8 ± 0.4; P < 0.01) compared to corresponding HC. The HC from Sassari had higher androgen receptor (2.9 ± 0.2) compared to MS from Sassari (1.4 ± 0.3; P < 0.01), MS (1.3 ± 0.4; P < 0.01) and HC from Stockholm (1.2 ± 0.3; P < 0.01). MS from Sassari had lower cyclooxygenase‐1 compared to corresponding HC (5.1 ± 0.4 versus 6.6 ± 0.3; P < 0.01) and lower prostaglandin‐E (−0.03 ± 0.5) compared to the HC (1.4 ± 0.5; P < 0.05) and MS (2.7 ± 0.4; P < 0.05) and HC from Stockholm (1.9 ± 0.4, P < 0.001). Our findings identify LXRs and their related molecules as being involved in MS from Stockholm but not from Sassari, while sex hormone receptors seem to be involved in MS in Sassari. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169544/ doi: 10.1111/j.0300-9475.2004.01423d.x id: cord-017520-r786yd6i author: Huber-Lang, Markus title: Inflammatory Changes and Coagulopathy in Multiply Injured Patients date: 2015-05-14 words: 7032.0 sentences: 356.0 pages: flesch: 34.0 cache: ./cache/cord-017520-r786yd6i.txt txt: ./txt/cord-017520-r786yd6i.txt summary: Severe tissue trauma leads to an early activation of several danger recognition systems, including the complement and the coagulation system, often resulting in an overwhelming almost synchronic proand anti-inflammatory response of the host. Although the immune response is associated with beneficial effects at the site of injury including the elimination of exogenous and endogenous danger molecules as well as the initiation of regenerative processes, an exaggerated systemic inflammatory response significantly contributes to posttraumatic complications such as multiple organ failure (MOF) and early death. The steps of an inflammatory reaction to trauma involve fluid phase mediators (cytokines, chemokines, coagulation-and complement activation products, oxygen radicals, eicosanoids, and nitric oxide (NO)) and cellular effectors (neutrophils, monocytes/macrophages, and endothelial cells) that translate the trauma-induced signals into cellular responses. abstract: Severe tissue trauma leads to an early activation of several danger recognition systems, including the complement and the coagulation system, often resulting in an overwhelming almost synchronic pro- and anti-inflammatory response of the host. Although the immune response is associated with beneficial effects at the site of injury including the elimination of exogenous and endogenous danger molecules as well as the initiation of regenerative processes, an exaggerated systemic inflammatory response significantly contributes to posttraumatic complications such as multiple organ failure (MOF) and early death. Besides pre-existing physical conditions, age, gender, and underlying comorbidities, surgical and anesthesiological management after injury is decisive for outcome. Improvements in surgical intensive care have increased number of patients who survive the initial phase after trauma. However, instead of progressing to normal recovery, patients often pass into persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The characterization and management of PICS will require new strategies for direct monitoring and therapeutic intervention into the patient’s immune function. In this chapter, we describe various factors involved in the inflammatory changes after trauma and aim to understand how these factors interact to progress to systemic inflammation, MOF, and PICS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122098/ doi: 10.1007/978-3-662-47212-5_4 id: cord-023387-tyeh14wz author: Hvas, C. L. title: Probiotic Bacteria Induce Regulatory Cytokine Production via Dendritic Cells date: 2008-06-28 words: 16893.0 sentences: 881.0 pages: flesch: 46.0 cache: ./cache/cord-023387-tyeh14wz.txt txt: ./txt/cord-023387-tyeh14wz.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Probiotic bacteria, e.g. Lactobacillus spp., may improve diseases such as chronic inflammatory bowel disease. We examined cytokine production and phenotypic change after in vitro stimulation of T cells from healthy volunteers using different probiotic strains. Methods: T cells were cultured from colonic biopsies from eight healthy volunteers (Agnholt and Kaltoft, Exp Clin Immunogenet 2001;18:213–25), and dendritic cells were matured from their peripheral blood mononuclear cells. T‐cell cultures were stimulated with autologous bacterial sonicate or strains of Lactobacillus spp., with and without the addition of dendritic cells. Cytokine levels (TNF‐α, IFN‐γ, IL‐10 and GM‐CSF) and phenotype (CD3, CD4, CD25 and CD69) were measured on day 4. Results: Lactobacillus spp. induced higher productions of TNF‐α and IL‐10 than did autologous bacteria. In presence of dendritic cells, the production of all cytokines increased. However, the increases of IFN‐γ and TNF‐α were more pronounced in wells with autologous bacteria than in wells with Lactobacillus spp. The addition of dendritic cells upregulated CD25 expression without simultaneous upregulation of CD69. The upregulation was pronounced after stimulation with Lactobacillus rhamnosus GG compared with autologous bacteria and other lactobacilli. Discussion: In presence of dendritic cells, autologous bacteria induced inflammatory cytokines, while probiotics mainly induced regulatory cytokines. Lactobacillus rhamnosus GG induced a regulatory phenotype (cd25(+)), in part mediated by dendritic cells. Future studies will address whether this shift to a CD25(+) phenotype represents a differentiation into competent regulatory T cells. In a clinical context, such cells might be used for treatment of inflammatory diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169507/ doi: 10.1111/j.0300-9475.2004.01423au.x id: cord-348855-lnltoj1n author: Iannaccone, Giulia title: Weathering the Cytokine Storm in COVID-19: Therapeutic Implications date: 2020-06-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. KEY MESSAGES: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19. url: https://doi.org/10.1159/000509483 doi: 10.1159/000509483 id: cord-023394-ptfjxpo6 author: Isa, A. title: Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection date: 2008-06-28 words: 16904.0 sentences: 872.0 pages: flesch: 46.0 cache: ./cache/cord-023394-ptfjxpo6.txt txt: ./txt/cord-023394-ptfjxpo6.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Background: Human parvovirus B19 (B19) is a ubiquitous pathogen, normally causing a mild self‐limiting disease, but also capable of causing both significant pathology and long‐term persistence. The small size and stability of the virus makes it suitable for mapping of the full breath and the kinetics of the cellular immune responses following acute viral infection. Methods: Five patients with acute primary B19 infection were included in the study and followed consecutively for up to 200 weeks. Cellular immune responses were mapped by IFNγ enzyme‐linked immunospot to overlapping peptides spanning the whole B19 genome. Results: In all five acutely infected patients, we were able to monitor the kinetics of a strong specific cellular immune reaction. Responses peaked at levels of 850–1850 SFC/million PBMCs, roughly corresponding to 0.3–0.6% B19‐specific CD8(+) cells circulating in peripheral blood at 10–80 weeks post‐infection. The responses in individual patients were directed to three or four different peptide pools, and the specificity was confined to the same CD8 epitopes present in the pools throughout the follow‐up period. The majority of responses were directed to the virus nonstructural protein, only two patients showed any response to the capsid proteins, elicited by the same epitope in both cases. Conclusion: The cellular immune responses to acute B19 infection are surprisingly narrow in distribution and remain at high levels for up to 80 weeks post‐infection. The initial epitope specificity is maintained, and the majority of responses target the virus nonstructural protein, which is not included in vaccine preparations, evaluated against the infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169519/ doi: 10.1111/j.0300-9475.2004.01423n.x id: cord-259367-2e998to9 author: Jacques, Alexandre title: Macrophage interleukin-6 and tumour necrosis factor-α are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a date: 2009-09-01 words: 6412.0 sentences: 370.0 pages: flesch: 51.0 cache: ./cache/cord-259367-2e998to9.txt txt: ./txt/cord-259367-2e998to9.txt summary: In this study, we demonstrate that the pro-inflammatory cytokines IL-6 and TNF-a, produced by MHV3-infected peritoneal macrophages, were induced by the fixation of protein S of MHV3 on TLR2 associated with regions enriched in heparan sulphate instead of CEA-CAM1a. 23, 44 To determine whether that the pro-inflammatory cytokines induced by L2-MHV3 in macrophages depend on viral fixation to regions enriched in heparan sulphate, resident peritoneal macrophages from C57BL/6 and Ceacam1a )/) mice were treated in vitro with heparin and infected further with L2-MHV3. To identify the intracellular signalling pathways involved in the TLR2/heparan sulphate region-dependent production of IL-6 and TNF-a, peritoneal macrophages from C57BL/6 and Ceacam1a )/) mice were treated with p38 (SB203580) and ERK-1/2 (U0126) MAPK inhibitors and infected in vitro with L2-MHV3. 21, 48, 49 However, we have demonstrated that viral fixation to the CEACAM1a receptor is not directly involved in the secretion of IL-6 and TNF-a by MHV3-infected peritoneal macrophages as these cytokines were also induced in cells from Ceacam1a )/) mice and regulated by the MAPK pathways. abstract: A rapid antiviral immune response may be related to viral interaction with the host cell leading to activation of macrophages via pattern recognition receptors (PPRs) or specific viral receptors. Carcinoembryonic cell adhesion antigen 1a (CEACAM1a) is the specific receptor for the mouse hepatitis virus (MHV), a coronavirus known to induce acute viral hepatitis in mice. The objective of this study was to understand the mechanisms responsible for the secretion of high-pathogenic MHV3-induced inflammatory cytokines. We report that the induction of the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-α in peritoneal macrophages does not depend on CEACAM1a, as demonstrated in cells isolated from Ceacam1a(−/−) mice. The induction of IL-6 and TNF-α production was related rather to the fixation of the spike (S) protein of MHV3 on Toll-like receptor 2 (TLR2) in regions enriched in heparan sulphate and did not rely on viral replication, as demonstrated with denatured S protein and UV-inactivated virus. High levels of IL-6 and TNF-α were produced in livers from infected C57BL/6 mice but not in livers from Tlr2(−/−) mice. The histopathological observations were correlated with the levels of those inflammatory cytokines. Depending on mouse strain, the viral fixation to heparan sulfate/TLR2 stimulated differently the p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in the induction of IL-6 and TNF-α. These results suggest that TLR2 and heparan sulphate receptors can act as new viral PPRs involved in inflammatory responses. url: https://www.ncbi.nlm.nih.gov/pubmed/19740307/ doi: 10.1111/j.1365-2567.2008.02946.x id: cord-022526-j9kg00qf author: Jones, Samuel L. title: Disorders of the Gastrointestinal System date: 2009-05-18 words: 108803.0 sentences: 5988.0 pages: flesch: 38.0 cache: ./cache/cord-022526-j9kg00qf.txt txt: ./txt/cord-022526-j9kg00qf.txt summary: Examination of the cardiovascular system (heart, peripheral pulse, and mucous membranes), lungs, and abdomen is essential to detect clinical signs of systemic inflammation from endotoxemia, coagulation disorders, dehydration, ileus, shock, and other abnormalities resulting from injury to the small or large intestine. Several reports suggest the efficacy of cisapride in managing intestinal disease in horses, including the resolution of persistent large colon impaction, treatment of equine grass sickness, and as a preventative for POI in horses after small intestinal surgery (0.1 mg/kg body mass intramuscularly during the postoperative period). 9 Primary role-players in DPJ-associated ileus include peritoneal inflammation, inflammatory cell migration/activation within the muscularis, small intestinal mechanical distention, and effects of endotoxin absorption. Diarrhea probably results from the severe ulceration and inflammation of the large intestine, causing increased secretion of water, electrolytes, and protein and decreased absorption of fluid. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158198/ doi: 10.1016/b0-72-169777-1/50015-9 id: cord-022631-s4n24xij author: Jonsson, M. V. title: Germinal Centres in Primary Sjögren''s Syndrome Indicate a Certain Clinical Immunological Phenotype date: 2008-06-28 words: 16905.0 sentences: 873.0 pages: flesch: 46.0 cache: ./cache/cord-022631-s4n24xij.txt txt: ./txt/cord-022631-s4n24xij.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Ectopic germinal centers (GCs) can be detected in the salivary glands of approximately 1/5 of patients with Sjögren's syndrome (SS) and appear in both primary and secondary SS. Previously, ectopic GC have been associated with increased local autoantibody production. The aim of this study was to determine whether GC in primary Sjögren's syndrome (pSS) defines a distinct seroimmunological phenotype. Retrospectively, a material of 130 haematoxylin and eosin‐stained paraffin‐embedded tissue sections of minor salivary gland tissue from patients with pSS was morphologically screened for the presence of ectopic GC. GC‐like lesions were detected in 33/130 (25%) of the pSS patients. Seventy‐two pSS patients lacking these structures (GC‐) were randomly selected for comparison. Focus score was significantly increased in the GC(+) patients compared to the GC(–) patients (P = 0.035). In the GC(+) group, 54.5% of the patients presented with anti‐Ro/SSA compared to 43.7% in the GC(–) group. Anti‐La/SSB was detected in 31.3% of the GC(+) patients compared to 25.7% of the GC(–) patients. Sixty‐one percentage of GC(+) patients presented with increased levels of IgG, a nonsignificant difference when compared to 39.4% in the GC(–) patients (P = 0.089). Levels of RF, ANA, ENA, IgM and IgA were similar in both patient groups, as were ESR and CRP. In conclusion, patients with ectopic GC have a higher focus score and more often present with autoantibodies and increased levels of IgG compared to pSS patients with regular focal infiltration (GC(–)). Our findings may indicate a certain seroimmunological phenotype and warrant for further prospective studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159356/ doi: 10.1111/j.0300-9475.2004.01423h.x id: cord-003686-1pfk4qve author: Kaneko, Naoe title: The role of interleukin-1 in general pathology date: 2019-06-06 words: 9464.0 sentences: 514.0 pages: flesch: 38.0 cache: ./cache/cord-003686-1pfk4qve.txt txt: ./txt/cord-003686-1pfk4qve.txt summary: The majority of NOD-like receptors such as NLRP1, NLRP3, NLRC4, NLRP6, and NLRP12 can interact with apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and caspase-1, and the resulting complex is a sensor of cell injury called "inflammasome", an interleukin (IL)-1β-processing platform that plays a crucial role in IL-1β maturation and secretion from cells. NLRP3 inflammasomes have also been reported to be involved in low-grade subclinical inflammation induced by chronic exposure to high levels of free fatty acids and glucose, leading to increased apoptosis and impaired insulin secretion of β-cells in obese type 2 diabetes mellitus (T2D) patients [102] [103] [104] . Canakinumab and anakinra were also effective for patients with Schnitzler syndrome, an adult-onset autoinflammatory disease characterized by focal urticaria and systemic inflammation including fever with bone and muscle pain, in the first placebo-controlled study, and several clinical trials are currently ongoing [186] [187] [188] [189] . abstract: Interleukin-1, an inflammatory cytokine, is considered to have diverse physiological functions and pathological significances and play an important role in health and disease. In this decade, interleukin-1 family members have been expanding and evidence is accumulating that highlights the importance of interleukin-1 in linking innate immunity with a broad spectrum of diseases beyond inflammatory diseases. In this review, we look back on the definition of “inflammation” in traditional general pathology and discuss new insights into interleukin-1 in view of its history and the molecular bases of diseases, as well as current progress in therapeutics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551897/ doi: 10.1186/s41232-019-0101-5 id: cord-023415-hhvmsn5b author: Karlsson, H. title: Pattern of Cytokine Responses to Gram‐Positive and Gram‐Negative Commensal Bacteria is Profoundly Changed when Monocytes Differentiate into Dendritic Cells date: 2008-06-28 words: 16909.0 sentences: 868.0 pages: flesch: 46.0 cache: ./cache/cord-023415-hhvmsn5b.txt txt: ./txt/cord-023415-hhvmsn5b.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: The normal gastrointestinal flora is crucial for the maturation of the acquired immunity via effects on antigen‐presenting cells (APCs). Here, we have investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal flora. Purified monocytes and monocyte‐derived DCs were stimulated with UV‐inactivated gram‐positive (Lactobacillus plantarum and Bifidobacterium adolescentis) and gram‐negative (Escherichia coli and Veillonella parvula) bacterial strains. Monocytes produced higher levels of IL‐12p70 and TNF, as detected by ELISA, in response to L. plantarum than to E. coli and V. parvula. In contrast, DCs secreted high amounts of IL‐12p70, TNF, IL‐6 and IL‐10 in response to E. coli and V. parvula but were practically unresponsive to L. plantarum and B. adolescentis. The lack of response to the gram‐positive strains correlated with a lower surface expression of Toll‐like reseptor 2 (TLR2) on DCs compared to monocytes. The surface expression of TLR4 on DCs was undetectable when analysed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that low TLR4 expression on DCs is sufficient to mount an inflammatory response to gram‐negative bacteria. IFN‐γ increased the expression of TLR4 on DCs and also potentiated the cytokine response to gram‐negative bacteria. Our results indicate that, when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, thereby becoming unresponsive to probiotic gram‐positive bacteria. These results may have important implications for the capacity of different groups of commensal bacteria to regulate mucosal and systemic immunity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169557/ doi: 10.1111/j.0300-9475.2004.01423at.x id: cord-262511-96xp1v0r author: Khabar, Khalid S. A. title: Rapid transit in the immune cells: the role of mRNA turnover regulation date: 2007-03-30 words: 6542.0 sentences: 342.0 pages: flesch: 43.0 cache: ./cache/cord-262511-96xp1v0r.txt txt: ./txt/cord-262511-96xp1v0r.txt summary: Post-transcriptional regulation contributes significantly to this rapid transit by several mechanisms, including mRNA stability modulation and translational control; collectively, they aim to control the expression of key gene products involved in the immune response. The stabilization of cytokine mRNA and other immune response gene products can occur by the activity of mRNA stabilization-promoting proteins such as human antigen (HuR) protein or by inactivation of RNA decay-promoting proteins such as the zinc finger protein, tristetraprolin (TTP). Traditionally, post-transcriptional regulation in innate immunity has been studied in response to the bacterial endotoxin, LPS, which binds CD14 in a complex with TLR4 on the surface of neutrophils and macrophages and initiates a cascade of signals that causes cell activation, the inflammatory response, and phagocytosis [35] . With the coordinated kinetics model, stabilizing RNA-binding proteins such as HuR can occur initially following immune cell activation, allowing rapid and early response of cytokine production. abstract: There have been recent, significant advances about the role of mRNA turnover in controlling gene expression in immune cells. Post‐transcriptional regulation of gene expression contributes to the characteristics of many of the processes underlying the immune response by ensuring early, rapid, and transient action. The emphasis of this review is on current work that deals with the regulation of mRNA decay during innate immunity against microbes and T cell activation as a model of the adaptive response. url: https://www.ncbi.nlm.nih.gov/pubmed/17400611/ doi: 10.1189/jlb.0207109 id: cord-252725-e3pazjdi author: Khalil, Ayman title: The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal date: 2020-10-15 words: 8759.0 sentences: 338.0 pages: flesch: 30.0 cache: ./cache/cord-252725-e3pazjdi.txt txt: ./txt/cord-252725-e3pazjdi.txt summary: In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID-19 through the enhancement of host immune response against viral infections by different biological mechanisms. Actually, data indicated that activation of the nuclear factor (NF)-κB transcription factor (NF-κB) signaling pathway represents a major contribution to the inflammation induced post SARS-CoV infection and that NF-κB inhibitors are promising antiviral drugs against infections caused by the virus and potentially other pathogenic human coronaviruses [8] . Moreover, it was found to reduce the reactive oxygenated species (ROS) produced during viral infection and subsequently decrease pro-inflammatory markers such as IL-8, TNF-α, IL-1β and IL-6 [25] and increases anti-inflammatory cytokines such as IL-10 [35] , indicating that it has clear antiviral effects on several respiratory and common cold viruses through its ability to reduce virus imputation, replication and viral load in vitro, as well as lung inflammation and airways hyper-responsiveness in vivo [29] . abstract: Polyphenols are a large family of more than 10,000 naturally occurring compounds, which exert countless pharmacological, biological and physiological benefits for human health including several chronic diseases such as cancer, diabetes, cardiovascular, and neurological diseases. Their role in traditional medicine, such as the use of a wide range of remedial herbs (thyme, oregano, rosemary, sage, mint, basil), has been well and long known for treating common respiratory problems and cold infections. This review reports on the most highlighted polyphenolic compounds present in up to date literature and their specific antiviral perceptive properties that might enhance the body immunity facing COVID-19, and other viral infectious diseases. In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID-19 through the enhancement of host immune response against viral infections by different biological mechanisms. Thus, polyphenols ought to be considered as a potential and valuable source for designing new drugs that could be used effectively in the combat against COVID‐19 and other rigorous diseases. url: https://doi.org/10.1007/s13659-020-00271-z doi: 10.1007/s13659-020-00271-z id: cord-300991-ipy24zxp author: Khan, Amira Sayed title: Obesity and COVID-19: Oro-Naso-Sensory Perception date: 2020-07-08 words: 5971.0 sentences: 314.0 pages: flesch: 47.0 cache: ./cache/cord-300991-ipy24zxp.txt txt: ./txt/cord-300991-ipy24zxp.txt summary: Through a recent upsurge of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, the clinical assessment of most of the coronavirus disease 19 (COVID-19) patients clearly presents a health condition with the loss of oro-naso-sensory (ONS) perception, responsible for the detection of flavor and savor. Hence, obesity represents a great risk factor for SARS-CoV-2 infection, as it may hide the viral-associated altered ONS symptoms, thus leading to a high mortality rate in these subjects. Moreover, the number of immunosuppressive T-regulatory, Treg (CD4 + CD25 + Foxp3 + ) cells and concentrations of IL-6, IL-10, and C-reactive protein (CRP) were upregulated in patients with severe COVID-19 [18] , suggesting that SARS-CoV-2 infection may lead to "over-immunosuppression" in the case of obesity ( Figure 1 ). SARS-CoV-2 infection may further aggravate the ONS functions; mask the obesity-induced inflammation, including loss of taste and smell; and render the obese subjects more vulnerable and prone to severe pathophysiological consequences such as RTI, leading to death. abstract: Through a recent upsurge of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, the clinical assessment of most of the coronavirus disease 19 (COVID-19) patients clearly presents a health condition with the loss of oro-naso-sensory (ONS) perception, responsible for the detection of flavor and savor. These changes include anosmia and dysgeusia. In some cases, these clinical manifestations appear even before the general flu-like symptoms, e.g., sore throat, thoracic oppression and fever. There is no direct report available on the loss of these chemical senses in obese COVID-19 patients. Interestingly, obesity has been shown to be associated with low ONS cues. These alterations in obese subjects are due to obesity-induced altered expression of olfacto-taste receptors. Besides, obesity may further aggravate the SARS-CoV-2 infection, as this pathology is associated with a high degree of inflammation/immunosuppression and reduced protection against viral infections. Hence, obesity represents a great risk factor for SARS-CoV-2 infection, as it may hide the viral-associated altered ONS symptoms, thus leading to a high mortality rate in these subjects. url: https://doi.org/10.3390/jcm9072158 doi: 10.3390/jcm9072158 id: cord-003013-h8txbd3p author: Kim, Sena title: Differential Regulation of Toll-Like Receptor-Mediated Cytokine Production by Unfolded Protein Response date: 2018-04-24 words: 3706.0 sentences: 205.0 pages: flesch: 35.0 cache: ./cache/cord-003013-h8txbd3p.txt txt: ./txt/cord-003013-h8txbd3p.txt summary: Under ER stress, unfolded protein response (UPR) signaling pathways participate in upregulating inflammatory cytokine production via NF-kappaB, MAPK, and GSK-3β. Toll-like receptor (TLRs) can recognize pathogenassociated molecular patterns (PAMPs) and dangerassociated molecular patterns (DAMPs) and induce TLRmediated intracellular signaling cascades to eliminate the pathogens through the production of proinflammatory cytokines including TNF-α, IL-6, IL-1β, and IL-8, but its uncontrolled activation can damage the host [9] . ER stress has been shown to regulate proinflammatory cytokine production, which are mediated by TLR signaling cascade components such as NF-kappaB, MAPK, and GSK-3β. In addition, ER stress shares TLR-mediated signaling components with pro-and anti-inflammatory cytokine productions, leading to the activation of NF-kappaB and MAPKs. The XBP1 deletion or chemical chaperone treatment in macrophages alleviates proinflammatory cytokine production by LPS. Toll-like receptor-mediated activation of intracellular signaling pathways results in increased production of proinflammatory cytokines including TNF-α, IL-6, and IL-1β. Endoplasmic reticulum stress-induced IRE1α activation mediates cross-talk of GSK-3β and XBP-1 to regulate inflammatory cytokine production abstract: The ability of the host immune response is largely mediated by the proinflammatory cytokine production. Physiological and pathological conditions of endoplasmic reticulum (ER) trigger unfolded protein response and contribute to the development or pathology of inflammatory diseases. Under ER stress, unfolded protein response (UPR) signaling pathways participate in upregulating inflammatory cytokine production via NF-kappaB, MAPK, and GSK-3β. Moreover, it has been suggested that ER stress crosstalks with toll-like receptor (TLR) signaling pathway to promote the production of proinflammatory cytokines. In addition, TLR stimulation can lead to UPR activation to promote inflammation. In this review, we will cover how proinflammatory cytokine production by UPR signaling can be induced or amplified in the presence or absence of TLR activation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941770/ doi: 10.1155/2018/9827312 id: cord-267270-r17z4d8x author: Kipar, A. title: Age-related dynamics of constitutive cytokine transcription levels of feline monocytes date: 2005-01-18 words: 2695.0 sentences: 141.0 pages: flesch: 53.0 cache: ./cache/cord-267270-r17z4d8x.txt txt: ./txt/cord-267270-r17z4d8x.txt summary: However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15 mo to 10 yr) were examined for transcription of IL-1β, IL-6, IL-10, IL-12 p40 and TNF-α by real-time PCR. One previous study actually showed significantly increased constitutive production of IL-1b and IL-6 in circulating monocytes of older female compared to young adult female human individuals, whereas no changes in the constitutive TNF-a production were observed (Sadeghi et al., 1999) . It seems plausible that despite increased or similar constitutive cytokine transcription, monocytes of older cats might exhibit an impaired reactive activation after virus infection (Kipar et al., 2005) . abstract: Monocytes/macrophages are central mediators of inflammation and immunity and therefore of major interest in the study of immunosenescence. In healthy adult cats, monocytes have been shown to constitutively transcribe pro- and anti-inflammatory cytokines. However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15 mo to 10 yr) were examined for transcription of IL-1β, IL-6, IL-10, IL-12 p40 and TNF-α by real-time PCR. Transcription levels of cytokines varied and were generally highest for IL-1β. For IL-1β, IL-6 and IL-12 p40, both young and old cats exhibited highest levels. The age association was significant. TNF-α appeared to be transcribed at similar levels over the examination period, whereas IL-10 tended to decline with age but without any statistical significant differences. The observed age association of the constitutive transcription of some cytokines indicates a drop in monocyte activities from youth to middle age, which is then followed by a (progressive) increase with increasing age. This provides evidence that monocytes are in part responsible for the pro-inflammatory status observed with ageing. url: https://api.elsevier.com/content/article/pii/S0531556505000021 doi: 10.1016/j.exger.2004.12.007 id: cord-023410-eblcf902 author: Kollgaard, T. M. title: Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation date: 2008-06-28 words: 16915.0 sentences: 872.0 pages: flesch: 46.0 cache: ./cache/cord-023410-eblcf902.txt txt: ./txt/cord-023410-eblcf902.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Allogeneic bone marrow transplantation (BMT) is a potentially curative therapy for patients with haematologic malignancies. Several lines of evidence demonstrate that donor T cells are involved in the antitumour effects observed after BMT. Thus, patients receiving T‐cell‐depleted BMT have a higher risk of leukaemia relapse compared to patients receiving nonmanipulated BMT, and patients experiencing graft‐versus‐host disease (GVHD) have a lower risk of disease relapse than patients who do not experience GVHD. Although the importance of donor T cells for the curative action of BMT has been established, the exact mechanisms and molecules involved in this graft‐versus‐tumour effect remain largely unknown. In a recently initiated project, we have conducted a longitudinal study of T‐cell clonotypes in patients who received peripheral blood stem cell grafts after nonmyeloablative conditioning. Peripheral blood samples were obtained sequentially after transplant, and the mononuclear cells (MNCs) were isolated and cryopreserved. CD8(+) T cells were isolated from the MNCs by use of immunomagnetic beads or FACS and analysed for the presence of clonally expanded cells by T‐cell receptor clonotype mapping based on RT‐PCR and denaturing gradient gel electrophoresis (DGGE). Using this gel‐based methodology, clonally expanded T cells were monitored after transplant and compared to the clinical data of the patients. The preliminary results demonstrates the presence of clonally expanded CD8(+) T cells at all time points analysed. Furthermore, a number of clonotypes persisted for more than 6 months, and other clonotypes emerged during this period. The appearance of newly emerged clonotypes which coincided with clinical GVHD could indicate a role for these T cells in the pathogenesis of GVHD. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169548/ doi: 10.1111/j.0300-9475.2004.01423bm.x id: cord-023393-8nye3nc8 author: Krarup, A. title: Mannan‐Binding Lectin, L‐Ficolin and H‐Ficolin Selectively Binds to Different Bacteria date: 2008-06-28 words: 16820.0 sentences: 864.0 pages: flesch: 46.0 cache: ./cache/cord-023393-8nye3nc8.txt txt: ./txt/cord-023393-8nye3nc8.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Mannan‐binding lectin (MBL), L‐ficolin and H‐ficolin are pattern recognition molecules of the innate immune system. We investigated the ability of these molecules to bind to different serotypes and noncapsulated variants of Streptococcus pneumonia and Staphylococcus aureus. We found that MBL binds to noncapsulated S. aureus strain (Wood) but not any of the examined S. pneumoniae serotypes. L‐ficolin binds to some capsulated S. pneumoniae serotypes (11A, 11D and 11F) as well as some capsulated S. aureus serotypes (Type‐1, ‐8, ‐9, ‐11 and ‐12). H‐ficolin does not bind to any of the examined S. pneumoniae and S. aureus serotypes included in this study but did bind to a strain of Aerococcus viridans. When bound to bacteria, MBL and H‐ficolin initiated activation of complement factor C4, whereas L‐ficolin did not. During this study, quantitative assays for the three proteins were developed and the concentration in 97 plasma samples were determined and the median values were estimated at 0.8 μg of MBL/ml, 3.3 μg of L‐ficolin/ml and 18.4 μg of H‐ficolin/ml, respectively. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169518/ doi: 10.1111/j.0300-9475.2004.01423al.x id: cord-023438-g0k0vvdc author: Krog, J. title: The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells, with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets date: 2008-06-28 words: 16880.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023438-g0k0vvdc.txt txt: ./txt/cord-023438-g0k0vvdc.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Materials and methods: As an experimental physiological stress model, we examined the effects of hyperbaric exposure on peripheral blood mononuclear cells (PBMCs) obtained from venous blood drawn from eight divers during a simulated heliox saturation dive. Eight persons working in normobar atmosphere outside the pressurized chamber served as control donors. The spontaneous cytotoxicity of the PBMCs was estimated in a 4 h 51Cr‐release assay using k562 as NK‐sensitive target cells. The PBMCs were characterized, using 4‐colour flow cytometry, with special emphasis on the NK‐cell subsets. The data were statistically analysed using a multivariate regression model (Stata 8.2). P values <0.05 was considered statistically significant. Results: The estimated cytotoxicity increased significantly in both the group of divers and control donors during the dive (pdivers < 0.01 and pcontrols < 0.01). Although the cytotoxicity increased relatively more (P < 0.01) in the group of divers compared to the group of control donors between day 1 and 2. Discussion: The increased cytotoxicity of PBMC estimated in the group of divers indicate that parts of the cellular immune system are affected during the extreme physiological conditions induced during the initial phase of the presented experimental hyperbaric setup. The increase in cytotoxicity observed in the group of control donors could hypothetically reflect the stress level in persons working outside the pressurized chamber during the dive. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169595/ doi: 10.1111/j.0300-9475.2004.01423aa.x id: cord-301946-erzh30mt author: Kwak-Kim, Joanne title: COVID-19 and immunomodulation treatment for women with reproductive failures date: 2020-06-12 words: 5604.0 sentences: 335.0 pages: flesch: 42.0 cache: ./cache/cord-301946-erzh30mt.txt txt: ./txt/cord-301946-erzh30mt.txt summary: With the Coronavirus Disease 2019 (COVID-19) pandemic, patient care has been significantly challenged not only for the COVID-19 cases but for the others, including pregnant women with a history of reproductive failures (RF), such as recurrent pregnancy losses (RPL), repeated implantation failures (RIF), with immune etiologies including autoimmune diseases, cellular immune dysfunction, and rheumatic conditions. SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus), which caused the SARS outbreak in 2003, infects macrophages and T cells (Perlman and Dandekar 2005) and induces various cytokines, such as type I IFN, TNF-α, IL-1, etc., and B cell-related antibodies (Prompetchara et al. With the currently available data, it is unlikely that the use of IVIg in patients with RFI will impact the chances of contracting the disease or negatively affect the clinical course in women with COVID-19 infection during pregnancy. abstract: COVID-19 pandemic is affecting various areas of health care, including human reproduction. Many women with reproductive failures, during the peri-implantation period and pregnancy, are on the immunotherapy using immune modulators and immunosuppressant due to underlying autoimmune diseases, cellular immune dysfunction, and rheumatic conditions. Many questions have been raised for women with immunotherapy during the COVID-19 pandemic, including infection susceptibility, how to manage women with an increased risk of and active COVID-19 infection. SARS-CoV-2 is a novel virus, and not enough information exists. Yet, we aim to review the data from previous coronavirus outbreaks and current COVID-19 and provide interim guidelines for immunotherapy in women with reproductive failures. url: https://www.ncbi.nlm.nih.gov/pubmed/32603991/ doi: 10.1016/j.jri.2020.103168 id: cord-002209-xs6qigg4 author: Kıray, Hülya title: The multifaceted role of astrocytes in regulating myelination date: 2016-09-17 words: 7509.0 sentences: 355.0 pages: flesch: 35.0 cache: ./cache/cord-002209-xs6qigg4.txt txt: ./txt/cord-002209-xs6qigg4.txt summary: In experimental allergic encephalomyelitis (EAE), a widely used animal model of MS, where demyelination is induced by myelin antigens, administered together with adjuvant that contains bacterial components (Traugott and Lebon, 1988; Tsukada et al., 1991; Villarroya et al., 1996) , GFAP expression was seen on more numerous and much larger astrocytic processes in chronic lesions compared to normal appearing white matter (Webster et al., 1985; Eng et al., 1971) . The milder "activated" astrocytes can secrete a range of factors including; neurotrophic factors, growth factors, and cytokines that will stimulate re/myelination by promoting neuronal survival, neurite outgrowth, neurogenesis, and/ or oligodendrocyte precursor cell (OPC) survival, proliferation, and/or maturation. Conversely astrocytes that tend to have a more severe "reactive" phenotype, possibly induced by proinflammatory cytokines/CNS tissue damage, may secrete cytokines and chemokines that lead to myelin and oligodendrocyte damage in vitro, suppress remyelination, delay disease recovery in experimental autoimmune encephalomyelitis (EAE), and suppress myelination in myelinating embryonic rat mixed spinal cord cultures. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury abstract: Astrocytes are the major glial cell of the central nervous system (CNS), providing both metabolic and physical support to other neural cells. After injury, astrocytes become reactive and express a continuum of phenotypes which may be supportive or inhibitory to CNS repair. This review will focus on the ability of astrocytes to influence myelination in the context of specific secreted factors, cytokines and other neural cell targets within the CNS. In particular, we focus on how astrocytes provide energy and cholesterol to neurons, influence synaptogenesis, affect oligodendrocyte biology and instigate cross-talk between the many cellular components of the CNS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019113/ doi: 10.1016/j.expneurol.2016.03.009 id: cord-023445-c4tqioz1 author: Lauridsen, C. title: Supplementation of Vitamin C to Weaner Diets Increases IgM Concentration and Improves the Biological Activity of Vitamin E in Alveolar Macrophages date: 2008-06-28 words: 16947.0 sentences: 870.0 pages: flesch: 46.0 cache: ./cache/cord-023445-c4tqioz1.txt txt: ./txt/cord-023445-c4tqioz1.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Vitamins E and C have been found to increase the cellular and humeral immunity of pigs. Vitamin E deficiency has also been found to predispose pigs to different diseases, E. coli infection is one among them. After weaning, the vitamin E status of pigs often decreases to a critical low level. In this experiment, we studied whether vitamin C supplementation would be a possible feeding strategy to optimize the immune status of weaners. The interaction between vitamin E and C is interesting due to the reported sparing action on vitamin E or synergism between these to vitamins. Piglets were weaned at day 28 of age from sows fed increasing dietary vitamin E during lactation, and piglets were during the following 3 weeks fed either a control diet or this diet supplemented with 500 mg STAY‐C per kg. Blood sampling was obtained weekly from day 28 and until day 49 of age. On the same days, one piglet per dietary treatment was killed and alveolar macrophages (AM) were harvested. Vitamin C supplementation increased the concentration of IgM in serum of piglets throughout the weaning period. Although the vitamin E concentration in AM decreased with increasing age of the piglets, the concentration was numerically higher in piglets of sows fed the high dietary level of vitamin E. However, vitamin C supplementation tended to increase the total AM concentration of vitamin E after weaning and increased the proportion of the biologically most active isomer of vitamin E [RRR‐(α‐tocopherol)] in the AM. The eicosanoid synthesis by AM was not influenced by the vitamin C supplementation, but the synthesis of leukotriene B4 was decreased 2 weeks after weaning compared to other days of AM harvesting. In conclusion, dietary vitamin C supplementation improved the immune responses of piglets after weaning. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169619/ doi: 10.1111/j.0300-9475.2004.01423u.x id: cord-009326-dvhkk405 author: Lee, Jae Min title: Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation date: 2020-03-14 words: 6438.0 sentences: 359.0 pages: flesch: 51.0 cache: ./cache/cord-009326-dvhkk405.txt txt: ./txt/cord-009326-dvhkk405.txt summary: title: Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation PRE inhibited TNF-α-induced NF-κB transcriptional activity in the NF-κB luciferase assay and pro-inflammatory genes'' expression by blocking phosphorylation of IκB and NF-κB in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-κB phosphorylation and pro-inflammatory genes'' expression. To investigate the effects of PRE on inflammation, we first tested NF-κB transcriptional activity of TPRE because NF-κB is an essential regulator of pro-inflammatory response ( Figure S1 ). Together, these results strongly suggest that PRE suppresses TNF-α-mediated pro-inflammatory gene expression by activating AMPK. Together, these results strongly suggest that PRE suppresses TNF-α-mediated pro-inflammatory gene expression by activating AMPK. abstract: The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-α-induced NF-κB transcriptional activity in the NF-κB luciferase assay and pro-inflammatory genes’ expression by blocking phosphorylation of IκB and NF-κB in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-κB phosphorylation and pro-inflammatory genes’ expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes’ expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146562/ doi: 10.3390/nu12030773 id: cord-332071-bqvn3ceq author: Lee, Jeong Seok title: Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 date: 2020-07-10 words: 7099.0 sentences: 412.0 pages: flesch: 53.0 cache: ./cache/cord-332071-bqvn3ceq.txt txt: ./txt/cord-332071-bqvn3ceq.txt summary: In a murine model of SARS-CoV infection, a delayed, but considerable type I IFN (IFN-I) response CORONAVIRUS Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 (Page numbers not final at time of first release) 2 promotes the accumulation of monocytes-macrophages and the production of pro-inflammatory cytokines, resulting in lethal pneumonia with vascular leakage and impaired virusspecific T-cell responses (10) . To examine the host immune responses in a cell type-specific manner, we subjected 59,572 cells to t-distributed stochastic neighbor embedding (tSNE) based on highly variable genes using the Seurat package (17) and identified 22 different clusters unbiased by patients or experimental batches of scRNA-seq (Fig. 1A, Fig. S1D ). First, we combined both mild and severe COVID-19 as a COVID-19 group and identified disease-specific changes in genes for each cell type compared to the healthy donor group using model-based analysis of single cell transcriptomics (MAST) (18) . abstract: Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19. url: https://doi.org/10.1126/sciimmunol.abd1554 doi: 10.1126/sciimmunol.abd1554 id: cord-308008-s2t11l3h author: Limonta, Daniel title: Apoptotic mediators in patients with severe and non‐severe dengue from Brazil date: 2013-10-29 words: 6077.0 sentences: 320.0 pages: flesch: 49.0 cache: ./cache/cord-308008-s2t11l3h.txt txt: ./txt/cord-308008-s2t11l3h.txt summary: Therefore, plasma levels of the three proapoptotic mediators Fas ligand (FasL), tumor necrosis factor-a (TNF-a), and TNF-related apoptosis-inducing ligand (TRAIL) were measured in dengue patients. Previous studies of dengue infection have shown apoptosis in lymphocytes [Mongkolsapaya et al., 2003; Myint et al., 2006] , monocytes [Torrentes-Carvalho et al., 2009; Levy et al., 2010] , and peripheral blood mononuclear cells (PBMCs) [Jaiyen et al., 2009] . The other proteins studied, plasma Survivin and PBMCs lysate proteins, are IAPs. Our data suggest that TRAIL could be involved with apoptosis induction of blood lymphocytes and could also contribute to the antiviral response. In the present study, elevated TRAIL levels were observed in patients with dengue without warning signs compared to those with severe dengue and control subjects. The findings in the present work, which used the revised WHO dengue classification, suggest that the antiviral action of TRAIL that was shown previously in cell culture [Warke et al., 2008b] , may also occur in vivo and hence the likely increased severity of dengue in patients lacking an elevated TRAIL production. abstract: Despite being the most significant arboviral disease worldwide, dengue has no antiviral treatment or reliable severity predictors. It has been shown that apoptotic cells from blood and tissues may be involved in the complex pathogenesis of dengue. However, very little is known about the interplay between proapoptotic and antiapoptotic mediators in this disease. Therefore, plasma levels of the three proapoptotic mediators Fas ligand (FasL), tumor necrosis factor‐α (TNF‐α), and TNF‐related apoptosis‐inducing ligand (TRAIL) were measured in dengue patients. Patients were classified according to the World Health Organization classification of dengue revised in 2009. Additionally, inhibitors of apoptosis protein (IAPs) were determined in plasma (Survivin) and peripheral blood mononuclear cells (PBMCs) lysates (cIAP‐1, cIAP‐2, XIAP). Levels of apoptotic proteins in plasma were correlated with counts of blood cells. FasL and TRAIL levels were elevated in dengue patients without warning signs when compared to patients with severe dengue and controls. Dengue patients with warning signs showed decreased levels of Survivin compared to patients with severe dengue and controls. TRAIL was inversely correlated with counts of lymphocyte subsets. In contrast, Survivin was positively correlated with leukocyte counts. There was a trend of elevated IAPs levels in PBMCs of patients with severe dengue. The results suggest a likely antiviral effect of TRAIL in dengue. It appears that TRAIL might be involved with apoptosis induction of lymphocytes, whereas IAPs might participate in protecting leukocytes from apoptosis. Further research is needed to explore the interactions between pro and antiapoptotic molecules and their implications in dengue pathogenesis. J. Med. Virol. 86:1437–1447, 2014. © 2013 Wiley Periodicals, Inc. url: https://doi.org/10.1002/jmv.23832 doi: 10.1002/jmv.23832 id: cord-023935-o2ffxgnn author: Lorts, Angela title: Sepsis date: 2011-12-16 words: 11110.0 sentences: 510.0 pages: flesch: 38.0 cache: ./cache/cord-023935-o2ffxgnn.txt txt: ./txt/cord-023935-o2ffxgnn.txt summary: SIRS i s a state of infl ammatory/ immune activation and is based on the presence of at least two of the four following clinical criteria: Temperature >38°C or <36°C, heart rate >90th percentile for age, respiratory rate >90th percentile for age, or hyperventilation to PaCO 2 < 32 mm Hg. The defi nition attempts to "capture" all patients at risk for the subsequent development of severe sepsis or septic shock. Among these, the nuclear factor-k B (NF-k b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. Nuclear factork B (NFk b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. abstract: The health care provider faced with the management of a child with septic shock relies on a comprehensive understanding of the numerous disciplines embodied in the practice of pediatric critical care medicine. The child with septic shock may have simultaneous derangements in the function of virtually every system of the body including: cardiovascular, respiratory, immune, renal, coagulation, hepatic, metabolic and neurologic. The degree to which physiologic alterations are manifest in a given patient is variable and influenced by multiple host and non-host factors including: the developmental stage, the presence of co-morbidities, pathogen-related factors, and genetic influences on both the host inflammatory response as well as the response to pharmacologic agents, all combining to have a profound influence on outcome. The clinician must possess a systematic and multifaceted approach to these critically ill patients. The goal of this chapter is to provide a comprehensive description of the epidemiology, biology and pathophysiology (at both the cellular and organ level) of sepsis, as well as outlining the current principles of managing septic shock. It will be apparent that optimal management requires a strong working knowledge of cardiovascular physiology, infectious diseases, multiple organ interactions, immunity, coagulation, pharmacology, and the molecular biology of inflammation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178851/ doi: 10.1007/978-0-85729-923-9_27 id: cord-002079-jne14jqf author: MacParland, Sonya A. title: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date: 2016-05-27 words: 7182.0 sentences: 388.0 pages: flesch: 48.0 cache: ./cache/cord-002079-jne14jqf.txt txt: ./txt/cord-002079-jne14jqf.txt summary: Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. These data demonstrate that certain inflammatory stimuli (TNF-␣ and LPS), as well as ischemic injury, but not other cytokines (IL-6 and IL-10) can lead to enhanced hepatocyte USP18 expression and thereby inhibit IFN signaling. Huh7.5 cells and primary murine hepatocytes were treated with IFN-␣ (100 U/ml), TNF-␣ (20 ng/ml), LPS (100 ng/ml), IL-6 (100 ng/ml), or IL-10 (10 ng/ ml) over a 24-h time course, and USP18 expression was determined by quantitative PCR (qPCR) as previously described (8, 9) . abstract: Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states. IMPORTANCE Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections. Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses. In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886784/ doi: 10.1128/jvi.02557-15 id: cord-333650-4towah1t author: Malmo, Jostein title: Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date: 2016-05-12 words: 4659.0 sentences: 250.0 pages: flesch: 50.0 cache: ./cache/cord-333650-4towah1t.txt txt: ./txt/cord-333650-4towah1t.txt summary: Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. To determine the presence of antiviral cytokines in children infected with hMPV and controls, we initially investigated the expression of type I, II and III IFNs. Fig 1A shows that only A2 infected children had slightly elevated mRNA levels of the type I IFN-β compared to the controls. Fig 2 shows the mRNA expression of A) IκBα, a repressor gene induced by NF-κB activation [19] , B) IL-1β, C) IL-18 and D) NLRP3 in hMPV infected children and controls. A previous study comparing the expression of several inflammatory cytokines in hMPV, RSV and influenza virus, detected elevated levels of TNF-α, IL-6 and IL-1β protein in nasal washes from infants with RTI [9] . abstract: Human metapneumovirus (hMPV) causes severe airway infection in children that may be caused by an unfavorable immune response. The nature of the innate immune response to hMPV in naturally occurring infections in children is largely undescribed, and it is unknown if inflammasome activation is implicated in disease pathogenesis. We examined nasopharynx aspirates and blood samples from hMPV-infected children without detectable co-infections. The expression of inflammatory and antiviral genes were measured in nasal airway secretions by relative mRNA quantification while blood plasma proteins were determined by a multiplex immunoassay. Several genes were significantly up-regulated at mRNA and protein level in the hMPV infected children. Most apparent was the expression of the chemokine IP-10, the pro-inflammatory cytokine IL-18 in addition to the interferon inducible gene ISG54. Interestingly, children experiencing more severe disease, as indicated by a severity index, had significantly more often up-regulation of the inflammasome-associated genes IL-1β and NLRP3. Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. Our study is the first to demonstrate that inflammasome components are associated with increased illness severity in hMPV-infected children. url: https://doi.org/10.1371/journal.pone.0155484 doi: 10.1371/journal.pone.0155484 id: cord-023373-6wh1kb3p author: Melchjorsen, J. title: Differential Requirements for Toll‐Like Receptor Signalling for Induction of Chemokine Expression by Herpes Simplex Virus and Sendai Virus date: 2008-06-28 words: 16841.0 sentences: 866.0 pages: flesch: 46.0 cache: ./cache/cord-023373-6wh1kb3p.txt txt: ./txt/cord-023373-6wh1kb3p.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Toll‐like receptors (TLRs) are pattern recognition receptors of the innate immune system, which recognize molecular structures on pathogens or cellular stress‐associated molecules. TLR–ligand interactions trigger activation of inflammatory signal transduction and expression of genes involved in host defense. In this study, we have examined the requirement for different TLR adaptor molecules in virus‐induced chemokine expression and are currently trying to identify the TLR involved. We have found that both a herpesvirus [herpes simplex virus (HSV)] and a paramyxovirus (Sendai virus) require a functional genome to induce expression or proinflammatory chemokines in human and murine monocytic cell lines. For both viruses, this is independent of the TLR adaptor molecules TRIF and Mal. However, overexpression of the Vaccinia virus‐encoded inhibitor of TLR‐signalling A52R or dominant‐negative MyD88 totally inhibited HSV‐induced RANTES expression but only partially prevented Sendai virus from inducing this chemokine. This suggests that HSV‐induced RANTES expression occurs via a TLR pathways, whereas Sendai virus utilizes both TLR‐dependent and ‐independent pathways to stimulate expression of RANTES. We are currently trying to identify the TLRs involved. Data from these studies will also be presented at the meeting. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169484/ doi: 10.1111/j.0300-9475.2004.01423r.x id: cord-354492-6r6qs4pp author: Messina, Giovanni title: Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work date: 2020-04-28 words: 6880.0 sentences: 355.0 pages: flesch: 38.0 cache: ./cache/cord-354492-6r6qs4pp.txt txt: ./txt/cord-354492-6r6qs4pp.txt summary: Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes. In human infections with highly virulent respiratory viruses-such as avian influenza H5N1, H7N9, Severe Acute Respiratory Syndrome (SARS) coronavirus, and Coronavirus Disease-19 (COVID-19)-immunopathogenesis caused by the overproduction of pro-inflammatory cytokines may play an essential role in disease progression and mortality [3] . Finally, considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a modification of the dietary regimen in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of the patients, improving their outcomes. abstract: Background: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5–7%, and the percentage of positive patients admitted to intensive care units being 9–11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes. url: https://www.ncbi.nlm.nih.gov/pubmed/32354030/ doi: 10.3390/ijms21093104 id: cord-319121-et957lfl author: Mifflin, Lauren title: Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target date: 2020-07-15 words: 12596.0 sentences: 633.0 pages: flesch: 34.0 cache: ./cache/cord-319121-et957lfl.txt txt: ./txt/cord-319121-et957lfl.txt summary: However, as researchers continued to delve into the mechanisms governed by RIPK1, it has become apparent that RIPK1 inhibitors may offer key therapeutic options that anti-TNF therapies do not: first, RIPK1 inhibitors are safe in the central nervous system (CNS) as RIPK1 kinase does not signal through TNFR2 which has a protective role in the CNS 7 ; second, RIPK1 participates in a broader set of pro-inflammatory activities than those restricted to TNF 8 ; third, RIPK1 is regulated by a distinct set of signalling molecules that are genetically implicated in human autoimmune and autoinflammatory diseases, as discussed below, and thus patient stratification may be important in conducting clinical trials of RIPK1 inhibitors. Mouse models with cell lineage-specific A20 deficiency phenocopy different human inflammatory diseases, suggesting an important role for A20 in restricting RIPK1 activation in multiple tissues ( showed increased levels of pro-inflammatory cytokines, such as TNF, IL-1β and IL-6, and demonstrated clinical improvement after treatment with anti-TNF or anti-IL-1β therapy. abstract: Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a key mediator of cell death and inflammation. The unique hydrophobic pocket in the allosteric regulatory domain of RIPK1 has enabled the development of highly selective small-molecule inhibitors of its kinase activity, which have demonstrated safety in preclinical models and clinical trials. Potential applications of these RIPK1 inhibitors for the treatment of monogenic and polygenic autoimmune, inflammatory, neurodegenerative, ischaemic and acute conditions, such as sepsis, are emerging. This article reviews RIPK1 biology and disease-associated mutations in RIPK1 signalling pathways, highlighting clinical trials of RIPK1 inhibitors and potential strategies to mitigate development challenges. url: https://doi.org/10.1038/s41573-020-0071-y doi: 10.1038/s41573-020-0071-y id: cord-276564-o21ncldx author: Miller, R. title: COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity date: 2020-06-29 words: 3229.0 sentences: 205.0 pages: flesch: 44.0 cache: ./cache/cord-276564-o21ncldx.txt txt: ./txt/cord-276564-o21ncldx.txt summary: This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. Vulnerable patient groups would potentially be less likely or unable to ensure sufficient activation of SIRT1 due to low NAD + levels or associated nutritional deficiencies including Zn ++ , and as such contribute to an inability to control viral replication and reduce the uncontrolled expression of pro-inflammatory cytokines. abstract: The SARS-CoV-2 hyperinflammatory response is associated with high mortality. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD(+)) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. NAD(+) levels decline with age and are also reduced in conditions associated with oxidative stress as occurs with hypertension, diabetes and obesity. These groups have also been observed to have high mortality following infection with COVID-19. Further consumption of NAD(+) in a pre-existent depleted state is more likely to cause progression to the hyperinflammatory stage of the disease through its limiting effects on the production of SIRT1. This provides a unifying hypothesis as to why these groups are at high risk of mortality and suggests that nutritional support with NAD(+) and SIRT1 activators, could minimise disease severity if administered prophylactically and or therapeutically. The significance of this, if proven, has far-reaching consequences in the management of COVID-19 especially in third world countries, where resources and finances are limited. url: https://www.ncbi.nlm.nih.gov/pubmed/32758884/ doi: 10.1016/j.mehy.2020.110044 id: cord-020643-0yzkqykg author: Müller-Werdan, U. title: Schock date: 2006 words: 30645.0 sentences: 4322.0 pages: flesch: 46.0 cache: ./cache/cord-020643-0yzkqykg.txt txt: ./txt/cord-020643-0yzkqykg.txt summary: Auch dass nichtinfektiöse Noxen (Trauma, Pankreatitis, herzchirurgische Operationen mit der Herz-Lungen-Maschine) zu einem ganz ähnlichen klinischen Bild wie bei bakteri-ell ausgelöster Sepsis und septischem Schock führen können, spricht für eine mehr oder weniger gemeinsame Zytokin-/Mediatorendstrecke als verantwortliche Schädigungskaskade sowohl bei infektiösen als auch bei nichtinfektiösen (SIRS, . Eine Ausnahme von dieser Regel stellt die Hirndurchblutung dar, die in der Sepsis weiterhin die Fähigkeit zur Autoregulation beibehält: Bei Patienten mit Sepsis ist die Hirndurchblutung bereits vor der Ausbildung des Schockzustandes um ein Drittel reduziert, wobei diese Durchblutungseinschränkung jedoch nicht als Ursache der septischen Enzephalopathie angesehen wird. Im Koronargefäßsystem fällt dagegen der Widerstand noch stärker ab als in den anderen Organen und demzufolge ist die Koronarperfusion bei Patienten mit septischem Schock sogar häufi g erhöht (Dhainaut et al. Die Messung des zentralen Venendrucks ist bei kritisch Kranken, insbesondere Schockpatienten, für das hämodynamische Monitoring normalerweise nicht genügend, eine Abschätzung der linksventrikulären Vorlast kann damit nicht ausreichend sicher durchgeführt werden, ebenso wenig wie mit der klinischen Einschätzung allein. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143837/ doi: 10.1007/3-540-29425-2_6 id: cord-340741-bhxm4zua author: Nayak, Tapas Kumar title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date: 2019-04-12 words: 8025.0 sentences: 394.0 pages: flesch: 48.0 cache: ./cache/cord-340741-bhxm4zua.txt txt: ./txt/cord-340741-bhxm4zua.txt summary: title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. In summary, for the first time it has been shown that CHIKV triggers robust TNF production (a key mediator of CHIKV induced inflammation) in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and viral protein nsP2 interacts with both the MAPKs during infection. abstract: Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is endemic in different parts of the globe. The host macrophages are identified as the major cellular reservoirs of CHIKV during infection and this virus triggers robust TNF production in the host macrophages, which might be a key mediator of virus induced inflammation. However, the molecular mechanism underneath TNF induction is not understood yet. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV to address the above-mentioned question. It was observed that CHIKV induces both p38 and JNK phosphorylation in macrophages in a time-dependent manner and p-p38 inhibitor, SB203580 is effective in reducing infection even at lower concentration as compared to the p-JNK inhibitor, SP600125. However, inhibition of p-p38 and p-JNK decreased CHIKV induced TNF production in the host macrophages. Moreover, CHIKV induced macrophage derived TNF was found to facilitate TCR driven T cell activation. Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs in the macrophages. This observation was supported by the in silico protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future. url: https://doi.org/10.3389/fimmu.2019.00786 doi: 10.3389/fimmu.2019.00786 id: cord-023430-5zuewjv2 author: Nilkaeo, A. title: Interleukin‐18 Inhibition of Oral Carcinoma Cell Proliferation date: 2008-06-28 words: 16908.0 sentences: 866.0 pages: flesch: 46.0 cache: ./cache/cord-023430-5zuewjv2.txt txt: ./txt/cord-023430-5zuewjv2.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Interleukin‐18 (IL‐18), a pro‐inflammatory cytokine that is produced by both lymphoid and nonlymphoid cells, has a critical role in modulation of innate and adaptive immunity. Its primary function in stimulation of IFN‐γ production and stimulation of NK‐cell‐cytotoxic activities makes this cytokine a candidate for cancer immunotherapy. In oral cavity, this cytokine is produced by oral epithelia and carcinoma cells and is related to tumour regression in nude mice bearing salivary adenocarcinoma. However, direct effects of this cytokine on oral cancer cells have not been elucidated. In this project, we investigated IL‐18 effect on an oral carcinoma (KB) cell line. With RT‐PCR technique, KB‐cell line was found to express IL‐18 receptors (IL‐18Rα and IL‐18Rβ), indicating that this oral carcinoma line is a target for IL‐18 study. We showed that recombinant human IL‐18 inhibited KB‐cell proliferation by 17% at concentration of 100 ng/ml (P < 0.05), whereas LDH release by these cells in treatment group and control groups was comparable, indicating that IL‐18 suppression of cell proliferation was not mediated by the induction of cell death. To further address this hypothesis, we found that IL‐18 treatment did not induce apoptotic cell death, as studied by DNA laddering and TUNEL assays. In addition, expression pattern of cell death‐controlling genes (bcl‐2 and bax) was not altered by this cytokine. Findings in these studies indicated that suppression of KB‐cell proliferation may be attributed to control of cell cycle, growth arrest or induction of cell differentiation. The data presented in this project could provide an insight of how cancer cell directly responds to IL‐18, as this cytokine is an important regulator of anticancer mechanisms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169582/ doi: 10.1111/j.0300-9475.2004.01423bg.x id: cord-006610-me8rhkcg author: Nör, Jacques E. title: Role of endothelial cell survival and death signals in angiogenesis date: 1999 words: 9984.0 sentences: 559.0 pages: flesch: 35.0 cache: ./cache/cord-006610-me8rhkcg.txt txt: ./txt/cord-006610-me8rhkcg.txt summary: There is now convincing evidence that regulated patterns of endothelial cell survival and death, a process known as apoptosis, play a central role in the periodic remodeling of the vasculature, and in the timely evolution and regression of angiogenic responses. In this review we discuss the current evidence suggesting a role for inducers and inhibitors of angiogenesis as well as other mediators that modify endothelial cells functions in the survival and death of endothelial cells. Events that govern the survival and death of endothelial cells have emerged as major factors that contribute to angiogenic responses during embryonic development, in the maintenance of organ and tissue homeostasis in adult organisms, and in pathological conditions such as tumor development. Enhanced activity of protein kinase C was associated with the ability of bFGF to protect endothelial cells against apoptosis induced by growth factor deprivation [170] or ionizing radiation in vitro and in vivo [170±172]. Vascular Endothelial Growth Factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression abstract: Angiogenesis, the process of new microvessel development, is encountered in a select number of physiological processes and is central to the pathogenesis of a wide variety of diseases. There is now convincing evidence that regulated patterns of endothelial cell survival and death, a process known as apoptosis, play a central role in the periodic remodeling of the vasculature, and in the timely evolution and regression of angiogenic responses. In this review we discuss the current evidence suggesting a role for inducers and inhibitors of angiogenesis as well as other mediators that modify endothelial cells functions in the survival and death of endothelial cells. We also discuss how dysregulation of apoptosis can lead to aberrant angiogenesis as demonstrated in the pathogenesis of retinopathy of prematurity and cancer. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102109/ doi: 10.1023/a:1009053411094 id: cord-280599-7ixpqd5n author: OPENSHAW, P J M title: What does the peripheral blood tell you in SARS? date: 2004-04-01 words: 1227.0 sentences: 64.0 pages: flesch: 51.0 cache: ./cache/cord-280599-7ixpqd5n.txt txt: ./txt/cord-280599-7ixpqd5n.txt summary: However, cytokine release is often very local, as illustrated by studies of TNF production in patients with bacterial pneumonia that show TNF levels to be high in bronchial lavage fluid from the affected lung, but not in fluid from the contralateral lung or in serum [4] . More importantly, anti-TNF therapy works well in many patients with rheumatoid arthritis or juvenile RA, but measurement of cytokines in serum and synovial fluid does not show raised levels of TNF [9] . So, what can we expect to learn by profiling cytokine production or levels in blood samples from patients with inflammatory diseases? Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/15030507/ doi: 10.1111/j.1365-2249.2004.02448.x id: cord-283246-dj7teo89 author: Otsuka, Ryo title: Macrophage activation syndrome and COVID-19 date: 2020-08-06 words: 3224.0 sentences: 177.0 pages: flesch: 37.0 cache: ./cache/cord-283246-dj7teo89.txt txt: ./txt/cord-283246-dj7teo89.txt summary: Still, it is possible that the causative virus for COVID-19, SARS-CoV-2, infect with particular types of cells such as endothelial vessels in the lung, or alveolar wall or macrophages. MAS is typified by markedly upregulated expression of pro-inflammatory cytokines, which is called "cytokine storm." Without any therapeutic intervention, this strong inflammation results in severe tissue injury and, ultimately, patient death. Thus, the commencement of local inflammation induced by SARS-CoV-2 infection activates macrophages at that site, spreading rapidly to the entire lung, possibly due to the abundant expression of virus entry receptors, ACE2 and TMPRSS2 [36] . Severe cases of COVID-19 are often observed with ARDS, representing the MAS-like clinical and laboratory features. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in abstract: An emerging, rapidly spreading coronavirus SARS-CoV-2 is causing a devastating pandemic. As we have not developed curative medicine and effective vaccine, the end of this life-threatening infectious disease is still unclear. Severe COVID-19 is often associated with hypercytokinemia, which is typically found in macrophage activation syndrome. SARS-CoV-2 infection causes this strong inflammation within the lung and propagates to respiratory and, ultimately, systemic organ malfunction. Although we have not fully understood the physiological and pathological aspects of COVID-19, current research progress indicates the effectiveness of anti-cytokine therapy. Here, we summarize macrophage activation syndrome and its possible contribution to COVID-19, and cytokine targeted attempts in severe COVID-19 cases. url: https://doi.org/10.1186/s41232-020-00131-w doi: 10.1186/s41232-020-00131-w id: cord-297857-ybqj8z1r author: Petagna, L. title: Pathophysiology of Crohn’s disease inflammation and recurrence date: 2020-11-07 words: 6669.0 sentences: 307.0 pages: flesch: 37.0 cache: ./cache/cord-297857-ybqj8z1r.txt txt: ./txt/cord-297857-ybqj8z1r.txt summary: Crohn''s disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. The pathogenesis is also sustained by the interaction of these cells with integrins, adhesion molecules and multiple chemokines, responsible for the production of elevated levels of inflammatory cytokines, representing the target of immune and non-immune cells and the promotion of mucosal inflammation. A new Antimesenteric functional end-to-end Handsewn anastomosis: surgical prevention of anastomotic recurrence in Crohn''s disease Surgical recurrence at anastomotic site after bowel resection in Crohn''s disease: comparison of Kono-S and end-to-end anastomosis Surgical prevention of anastomotic recurrence by excluding mesentery in Crohn''s disease: the SuPREMe-CD study -a randomized clinical trial Inclusion of the mesentery in Ileocolic resection for Crohn''s disease is associated with reduced surgical recurrence abstract: Chron’s Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions influenced by a complex pathogenesis in which inflammation plays a key role. Crohn’s disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a T(H)1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence. url: https://www.ncbi.nlm.nih.gov/pubmed/33160400/ doi: 10.1186/s13062-020-00280-5 id: cord-295523-5pv7kw6i author: Picchianti Diamanti, Andrea title: Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity date: 2020-05-08 words: 7905.0 sentences: 390.0 pages: flesch: 39.0 cache: ./cache/cord-295523-5pv7kw6i.txt txt: ./txt/cord-295523-5pv7kw6i.txt summary: However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). We critically review the rationale for the adoption of immunosuppressive agents, commonly used in autoimmune diseases, in the treatment of SARS-CoV-2 infection and report current knowledge of ongoing studies. The exacerbated reaction to infections or to biological therapy is caused by the rapid recruitment of macrophages and neutrophils, which produce pro-inflammatory cytokines and alter the fragile balance between a controlled immune response and a host-damaging reaction. As of now, four clinical trials are recruiting patients with COVID-19, severe acute respiratory failure, and CRS, aiming at evaluating the safety and effectiveness of anakinra alone or in combination with anti-IL-6 agents (NCT04330638, NCT0432402, NCT04357366, NCT04339712). High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis abstract: On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk. url: https://www.ncbi.nlm.nih.gov/pubmed/32397174/ doi: 10.3390/ijms21093330 id: cord-005664-n4xv247l author: Plötz, Frans B. title: Mechanical ventilation alters the immune response in children without lung pathology date: 2002-01-15 words: 3292.0 sentences: 182.0 pages: flesch: 41.0 cache: ./cache/cord-005664-n4xv247l.txt txt: ./txt/cord-005664-n4xv247l.txt summary: In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-α and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. The major finding of the present study is that exposing infants with normal lung function to 2 h of volatile anesthetics, mechanical ventilation, and cardiac catheterization is associated with remarkable changes in immune responses. We observed a proinflammatory response in the lungs with a significant increase in TNF-α, while antiinflammatory cytokine concentrations in tracheal aspirates remained virtually unchanged, just above the detection level. abstract: Objective: This study was undertaken to examine the hypothesis that mechanical ventilation in association with anesthesia would alter the cytokine profile in infants without preexisting lung pathology. Design and setting: Prospective observational study in pediatric intensive care unit in a university hospital. Patients: Twelve infants who were subjected to an uncomplicated diagnostic cardiac catheterization procedure were studied. All subjects were ventilated with a volume control mode, 0.3 FIO(2), 4 cmH(2)O PEEP, and 10 ml/kg tidal volume. Volatile (servoflurane) anesthetics were given. Measurements and results: Tracheal aspirates and blood samples were obtained before and after 2 h of mechanical ventilation. In tracheal aspirates and in supernatants of stimulated whole-blood cultures cytokine concentrations were measured. In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-α and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. The functional capacity of peripheral blood leukocytes to produce INF-γ, TNF-α, and IL-6 in vitro was significantly decreased. This was accompanied by a significant decrease in the killing activity of natural killer cells. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. In the lungs the immune balance favors a proinflammatory response pattern without detectable concentrations of anti-inflammatory mediators. The Th1 immune response by peripheral blood leukocytes was decreased. The observed change in Th1/Th2 balance in favor of Th2 cytokine activity may be a systemic adaptation to the proinflammatory milieu in the lung. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095146/ doi: 10.1007/s00134-002-1216-7 id: cord-324949-sqy03dks author: Poe, Francis L. title: N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2 date: 2020-05-30 words: 3485.0 sentences: 208.0 pages: flesch: 47.0 cache: ./cache/cord-324949-sqy03dks.txt txt: ./txt/cord-324949-sqy03dks.txt summary: In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. Mediation of the viral load could occur through NAC''s ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death. The pathogenic factors of SARS-CoV-2 that could possibly be mediated by NAC are (1) T cell exhaustion, which manifests as lower counts and decreased functional capacity of CD4+ and CD8+ cells; (2) pro-inflammatory state via increase in TNF-ɑ, IL1β, IL18; and (3) modulation of viral activity through increased glutathione. Mediation of the viral load could occur through the ability of NAC to increase cellular redox status by maximizing the rate limiting step of glutathione synthesis, and thereby decreasing the effects of virally induced oxidative stress and cell death. abstract: COVID-19, a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread across the globe. Predisposing factors such as age, diabetes, cardiovascular disease, and lowered immune function increase the risk of disease severity. T cell exhaustion, high viral load, and high levels of TNF-ɑ, IL1β, IL6, IL10 have been associated with severe SARS-CoV-2. Cytokine and antigen overstimulation are potentially responsible for poor humoral response to the virus. Lower cellular redox status, which leads to pro-inflammatory states mediated by TNF-ɑ is also potentially implicated. In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. In human clinical trials, NAC can be used to replenish glutathione stores and increase the proliferative response of T cells. NAC has also been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials. Mediation of the viral load could occur through NAC’s ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death. We hypothesize that NAC could act as a potential therapeutic agent in the treatment of COVID-19 through a variety of potential mechanisms, including increasing glutathione, improving T cell response, and modulating inflammation. In this article, we present evidence to support the use of NAC as a potential therapeutic agent in the treatment of COVID-19. url: https://www.sciencedirect.com/science/article/pii/S0306987720308811?v=s5 doi: 10.1016/j.mehy.2020.109862 id: cord-271812-ldwb05xn author: Prasad, Ananda S. title: Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease(1)(2)(3) date: 2013-03-01 words: 12220.0 sentences: 617.0 pages: flesch: 49.0 cache: ./cache/cord-271812-ldwb05xn.txt txt: ./txt/cord-271812-ldwb05xn.txt summary: Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson''s disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. AE is a lethal, autosomal, recessive trait that usually occurs in infants of Italian, Armenian, or Iranian lineage 4 Abbreviations used: AB, b amyloid protein; AD, Alzheimer''s disease; AE, acrodermatitis enteropathica; APP, amyloid precursor protein; CRP, C-reactive protein; DC, dendritic cells; HAE, 4-hydroxyalkenal; HAEC, human vascular endothelial cell; HL-60, human promyelocytic leukemia cell line; ICAM-1, intercellular adhesion molecule 1; IFN, interferon; IGF-1, insulin-like growth factor 1; MDA, malondialdehyde; MNC, mononuclear cell; NF-kB, nuclear factor kB; oxLDL, oxidized LDL; PHA-P, phytohemagglutinin P; PMA, phorbol-12 myristate 13 acetate; ra, receptor antagonist; RDA, recommended daily allowance; ROS, reactive oxygen species; SCD, sickle cell disease; sIL-1 ra, soluble interleukin-1 receptor antagonist; THP-1, human monocytic leukemia cell line; TK, deoxythymidine kinase; VCAM-1, vascular cell adhesion molecule 1. abstract: The essentiality of zinc in humans was established in 1963. During the past 50 y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. The major factor contributing to zinc deficiency is high phytate-containing cereal protein intake in the developing world, and nearly 2 billion subjects may be zinc deficient. Conditioned deficiency of zinc has been observed in patients with malabsorption syndrome, liver disease, chronic renal disease, sickle cell disease, and other chronic illnesses. Major clinical problems resulting from zinc deficiency in humans include growth retardation; cell-mediated immune dysfunction, and cognitive impairment. In the Middle East, zinc-deficient dwarfs did not live beyond the age of 25 y, and they died because of intercurrent infections. In 1963, we knew of only 3 enzymes that required zinc for their activities, but now we know of >300 enzymes and >1000 transcription factors that are known to require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson’s disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent. url: https://academic.oup.com/advances/article-pdf/4/2/176/23736058/176.pdf doi: 10.3945/an.112.003210 id: cord-301102-jbjysyqm author: Priestnall, Simon L. title: Quantification of mRNA encoding cytokines and chemokines and assessment of ciliary function in canine tracheal epithelium during infection with canine respiratory coronavirus (CRCoV) date: 2009-01-15 words: 6022.0 sentences: 296.0 pages: flesch: 48.0 cache: ./cache/cord-301102-jbjysyqm.txt txt: ./txt/cord-301102-jbjysyqm.txt summary: title: Quantification of mRNA encoding cytokines and chemokines and assessment of ciliary function in canine tracheal epithelium during infection with canine respiratory coronavirus (CRCoV) This study aimed to quantify pro-inflammatory cytokine mRNAs following infection of canine air-interface tracheal cultures with CRCoV. This study aimed to quantify pro-inflammatory cytokine mRNAs following infection of canine air-interface tracheal cultures with CRCoV. The quantification of canine IL-6, IL-8 and TNF-a mRNA copies in CRCoV-inoculated cultures was presented as the logarithm of the fold change relative to control-inoculated cultures in the same dog at the same time point. In response to LPS, mRNA levels of TNF-a, IL-6 and IL-8 in cultures, were significantly increased from 24 h post-inoculation, relative to controls, indicating that the assay was sensitive enough to detect changes in cytokine mRNAs within this system. IHC revealed coronavirus antigen positive intra-cytoplasmic staining of ciliated epithelial and goblet cells within canine tracheas of both CRCoV-inoculated cultures and from naturally infected cases of CIRD. abstract: One of the first lines of defence against viral infection is the innate immune response and the induction of antiviral type I interferons (IFNs). However some viruses, including the group 2 coronaviruses, have evolved mechanisms to overcome or circumvent the host antiviral response. Canine respiratory coronavirus (CRCoV) has previously been shown to have a widespread international presence and has been implicated in outbreaks of canine infectious respiratory disease (CIRD). This study aimed to quantify pro-inflammatory cytokine mRNAs following infection of canine air-interface tracheal cultures with CRCoV. Within this system, immunohistochemistry identified ciliated epithelial and goblet cells as positive for CRCoV, identical to naturally infected cases, thus the data obtained would be fully transferable to the situation in vivo. An assay of ciliary function was used to assess potential effects of CRCoV on the mucociliary system. CRCoV was shown to reduce the mRNA levels of the pro-inflammatory cytokines TNF-α and IL-6 and the chemokine IL-8 during the 72 h post-inoculation. The mechanism for this is unknown, however the suppression of a key antiviral strategy during a period of physiologic and immunological stress, such as on entry to a kennel, could potentially predispose a dog to further pathogenic challenge and the development of respiratory disease. url: https://www.ncbi.nlm.nih.gov/pubmed/18977539/ doi: 10.1016/j.vetimm.2008.09.017 id: cord-023372-ft8cp9op author: Rahman, Q. K. title: The Immunomodulatory Effect of Heat Shock Protein 70: Immunization with a DNA Construct Based on the Malarial Antigen Fused with a Fragment of HSP 70 Primes for a Th‐1 Type of Response date: 2008-06-28 words: 16863.0 sentences: 874.0 pages: flesch: 46.0 cache: ./cache/cord-023372-ft8cp9op.txt txt: ./txt/cord-023372-ft8cp9op.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Finding an appropriate adjuvant for human vaccination is crucial. Heat shock proteins (HSPs) act as adjuvants when coadministered with peptide antigens or given as fusion proteins. However, there is a potential risk of autoimmunity when using the complete molecules, because HSPs are evolutionary conserved. To overcome this, we first evaluated the adjuvant effect against two different antigens of a less‐conserved fraction of Plasmodium falciparum HSP70 (Pf70C) and compared it to the whole HSP70 molecule from Trypanosoma cruzi (TcHSP70). We found that Pf70C exhibited similar adjuvant properties as the whole molecule. We later evaluated the adjuvant potential of Pf70C against the malarial antigen EB200 in a chimeric DNA construct. No appreciable levels of EB200‐specific antibodies were detected in mice immunized only with the DNA constructs. However, DNA primed the immune system, because subsequent challenge with the corresponding recombinant fusion proteins elicited a strong Th‐1 antibody response. In contrast, no priming effect was observed for ex vivo IFN‐γ production but stimulation with the HSP‐chimeric fusion protein induced a stronger secretion of IFN‐γin vitro than other proteins used. These results indicate that the use of HSPs is promising in the design of new vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169481/ doi: 10.1111/j.0300-9475.2004.01423aw.x id: cord-103625-p55ew8w7 author: Ramana, Chilakamarti V. title: Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date: 2020-08-14 words: 3320.0 sentences: 217.0 pages: flesch: 47.0 cache: ./cache/cord-103625-p55ew8w7.txt txt: ./txt/cord-103625-p55ew8w7.txt summary: Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Furthermore, Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients. In this study, transcription factor profiling in interferon-mediated gene expression data sets and RT-PCR revealed that Egr-1 was rapidly induced by IFN-α/β and TLR ligands in multiple cell types. Respiratory pathogens including coronaviruses (SARS-CoV-1 and 2) and influenza viruses regulated the expression of Egr-1 in human lung cell lines and in lung biopsies and peripheral blood cells of COVID-19 patients, These studies suggest that the regulation of Egr-1 may play an important role in the antiviral response and inflammatory disease. abstract: Respiratory virus infection is one of the leading causes of death in the world. Activation of the Jak-Stat pathway by Interferon-alpha/beta (IFN-α/β) in lung epithelial cells is critical for innate immunity to respiratory viruses. Genetic and biochemical studies have shown that transcriptional regulation by IFN-α/β required the formation of Interferon-stimulated gene factor-3 (ISGF-3) complex consisting of Stat1, Stat2, and Irf9 transcription factors. Furthermore, IFN α/β receptor activates multiple signal transduction pathways in parallel to the Jak-Stat pathway and induces several transcription factors at mRNA levels resulting in the secondary and tertiary rounds of transcription. Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Studies in mutant cell lines lacking components of the ISGF-3 complex revealed that IFN-β induction of Egr-1 was independent of Stat1, Stat2, or Irf9. Activation of the Mek/Erk-1/2 pathway was implicated in the rapid induction of Egr-1 by IFN-β in serum-starved mouse lung epithelial cells. Interrogation of multiple microarray datasets revealed that respiratory viruses including coronaviruses regulated Egr-1 expression in human lung cell lines. Furthermore, Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients. Rapid induction by interferons, TLR ligands, and respiratory viruses suggests a critical role for Egr-1 in antiviral response and inflammation with potential implications for human health and disease. url: https://doi.org/10.1101/2020.08.14.244897 doi: 10.1101/2020.08.14.244897 id: cord-013366-sbdtpsz6 author: Ramírez-Pérez, Sergio title: Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor date: 2020-09-21 words: 5749.0 sentences: 283.0 pages: flesch: 45.0 cache: ./cache/cord-013366-sbdtpsz6.txt txt: ./txt/cord-013366-sbdtpsz6.txt summary: Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both proand anti-inflammatory cytokines. The chemical molecule ST2825 acts as an inhibitor of MyD88 dimerisation and its activity has been demonstrated through the inhibition of TLR9-dependent CpG-regulated signalling, and inhibition of IL-12, IL-1β, IL-6 and tumor necrosis factor alpha (TNF-α) expression in LPS-stimulated RAW 264.7 cells [19] [20] [21] [22] . The present study shows that the specific inhibition of critical components in the IL-1 signalling pathway is not enough to avoid the secretion of inflammatory mediators, the above suggests that various MyD88-independent mechanisms could regulate the production of cytokines in PBMC. abstract: The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570868/ doi: 10.3390/molecules25184322 id: cord-269986-jdcw59r2 author: Regan, Andrew D. title: Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells date: 2009-02-05 words: 5516.0 sentences: 260.0 pages: flesch: 50.0 cache: ./cache/cord-269986-jdcw59r2.txt txt: ./txt/cord-269986-jdcw59r2.txt summary: Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors. To determine whether viral replication was required for FIPV-induced p38 MAPK activation, UV-inactivated virus was added to PFBM cells and analyzed by western blot as described above (Fig. 1B) . Overall these data indicate that production of the pro-inflammatory cytokine TNF-alpha in FIPVinfected PFBM cells is regulated by activation of the p38 MAPK pathway. In this study we show that infection by FIPV causes a rapid activation the p38 MAPK pathway in PFBM cells, and that this process directly regulates production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta. abstract: Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors. url: https://www.sciencedirect.com/science/article/pii/S0042682208007356 doi: 10.1016/j.virol.2008.11.006 id: cord-023402-8qfmo6rq author: Reinholdt, J. title: Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype‐Specific Human Monoclonal IgA1 Antibodies date: 2008-06-28 words: 17011.0 sentences: 882.0 pages: flesch: 46.0 cache: ./cache/cord-023402-8qfmo6rq.txt txt: ./txt/cord-023402-8qfmo6rq.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Bacteria‐specific IgA antibodies are efficient opsonins for neutrophils and mononuclear phagocytes, provided that the phagocytes express the Fca receptor (CD89). Expression of CD89 can be stimulated by inflammatory cytokines, activated complement factors and certain microbial components. In one study, unstimulated phagocytes were able to ingest IgA antibody‐treated pneumococci, but only in the presence of complement, which was found to be activated by the IgA antibodies along the alternative pathway. Pneumococci produce IgA1 protease that cleaves human IgA1, but not IgA2, molecules in the hinge region. This leaves IgA1 as Fabα (monovalent) deprived of Fcα which contains the docking site for CD89. IgA1 is the vastly predominant subclass of IgA in the upper airways and circulation of humans. Aims: To examine the effects of IgA1 protease activity and complement on phagocytosis of IgA antibody‐coated pneumococci by an unstimulated human phagocytic cell line (hl60). Materials and methods: IgA1 and IgA2 monoclonal antibodies to serotype 4 pneumococcal capsular polysaccharide (ps) were generated by heterohybridoma technique involving B cells from human vaccinees. Isogenic serotype 4 pneumococci with and without IgA1 protease activity, respectively, were obtained after inactivation of the iga gene of the TIGR4 strain. Opsonophagocytosis was quantitated using the assay described by Romero‐Steiner et al. Based on enumeration of surviving bacteria by culture. The integrity of IgA molecules was examined by western blotting. Results: Both IgA1 and IgA2 antibody to type‐4 polysaccharide‐induced phagocytosis of IgA1 protease‐deficient type‐4 pneumococci equally well in the absence as in the presence of complement. Iga1 antibody to type‐4 polysaccharide displayed a fourfold higher opsonophagocytosis titer against IgA1 protease deficient compared to homologous wildtype target bacteria. A similar effect of IgA1 protease activity of the target bacteria was not observed in a parallel experiment where IgA2 antibody to type‐4 polysaccharide served as opsonin. IgA1 antibody extracted from IgA1 protease‐producing target bacteria was almost exclusively in the form of Fabα. Conversely, IgA1 from protease‐deficient bacteria and IgA2 from both types of bacteria were intact. Conclusions: These results indicate that the IgA1 protease activity of S. neumoniae may help the bacteria escape IgA1 antibody‐mediated opsonophagocytosis. Besides, in these experiments, IgA‐mediated opsonophagocytosis was independent of complement. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169534/ doi: 10.1111/j.0300-9475.2004.01423t.x id: cord-007613-g4s0v8ra author: Rimstad, Espen title: Cloning, expression and characterization of biologically active feline tumour necrosis factor-α date: 2000-03-10 words: 4664.0 sentences: 265.0 pages: flesch: 58.0 cache: ./cache/cord-007613-g4s0v8ra.txt txt: ./txt/cord-007613-g4s0v8ra.txt summary: To assure that stimulated macrophage mRNA was the actual source for cDNA, cDNA derived by reverse transcription of mRNA from unstimulated macrophage cultures, as well as feline genomic DNA, were extracted and used as targets in separate and parallel PCRs. The amplified fragments generated by both the P 1 /P3 and P2/P3 primers were separately cloned into the plasmid vector pCRI1 (TA-cloning kit, Invitrogen), and the nucleotide sequences were determined by conventional dideoxy sequencing of both strands. Although some variation was evident between the four individual donor cats, rfTNF-a induced a dose related increase of IG2R and MHC class II antigen expression on the cell surface of in vitro stimulated feline PMBCs (Fig. 6 ) . Tumor necrosis factor a induces expression of human immunodeticiency virus in a chronically infected T-cell clone Tumor necrosis factor a induces proteins that bind specifically to kB-like enhancer elements and regulate interleukin 2 receptor a-chain gene expression in primary human T-lymphocytes abstract: We report the cloning, expression and characterization of biologically active feline tumour necrosis factor-α (fTNF-α). Messenger RNA was extracted from feline peritoneal macrophage cultures and used to synthesize cDNA for polymerase chain reaction (PCR) amplification. The PCR products were cloned into the plasmid vector pCRII and sequenced, showing 99.3% homology with a published fTNF-α gene sequence. Subcloning into the vector pGEX-2T and subsequent expression resulted in a 43 kDa fusion protein of fTNF-α and glutathione S-transferase (GST). Thrombin cleavage of the fusion protein yielded a 17 kDa protein. This protein cross-reacted with a monoclonal anti-human TNF-α antibody in Western blotting, but not with a polyclonal anti-murine TNF-α serum. Recombinant fTNF-α (rfTNF-α) and rfTNF-α-GST had a CD(50) of 15 ng ml(−1) and 230 ng ml(−1), respectively, in the L929 cytotoxicity assay. Cats given rfTNF-α-GST intravenously manifested the typical biological effects of TNF-α, including fever, depression, and piloerection. The rfTNF-α-GST upregulated IL-2 receptor and MHC-II antigen expression on peripheral blood mononuclear cells stimulated in vitro, but had no effect on TNF-α receptor and MHC-I antigen expression. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119607/ doi: 10.1016/0165-2427(94)05345-s id: cord-308433-vrkdtrfz author: Roberts, Ceri A. title: TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells date: 2017-02-15 words: 7283.0 sentences: 409.0 pages: flesch: 56.0 cache: ./cache/cord-308433-vrkdtrfz.txt txt: ./txt/cord-308433-vrkdtrfz.txt summary: Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. To investigate whether TNF blockade regulates IL-10 expression in different pro-inflammatory cytokine-producing CD4 + T cells, we isolated CD4 + T cells from PB of healthy donors and cocultured the cells with CD14 + monocytes and anti-CD3 mAb (100 ng/ml) in the absence or presence of the anti-TNF mAb adalimumab (1 µg/ml), as previously described (20) . abstract: CD4(+) and CD8(+) effector T cell subpopulations can display regulatory potential characterized by expression of the prototypically anti-inflammatory cytokine IL-10. However, the underlying cellular mechanisms that regulate expression of IL-10 in different T cell subpopulations are not yet fully elucidated. We recently showed that TNF inhibitors (TNFi) promote IL-10 expression in human CD4(+) T cells, including IL-17(+) CD4(+) T cells. Here, we further characterized the regulation of IL-10 expression via blockade of TNF signaling or other cytokine/co-stimulatory pathways, in human T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4(+) T cell/monocyte cocultures led to increased percentages of IL-10(+) cells in pro-inflammatory IL-17(+), IFNγ(+), TNFα(+), GM-CSF(+), and IL-4(+) CD4(+) T cell subpopulations. Conversely, exogenous TNFα strongly decreased IL-10(+) cell frequencies. TNF blockade also regulated IL-10 expression in CD4(+) T cells upon antigenic stimulation. Using time course experiments in whole peripheral blood mononuclear cell (PBMC) cultures, we show that TNF blockade maintained, rather than increased, IL-10(+) cell frequencies in both CD4(+) and CD8(+) T cells following in vitro stimulation in a dose- and time-dependent manner. Blockade of IL-17, IFNγ, IL-6R, or CD80/CD86-mediated co-stimulation did not significantly regulate IL-10 expression within CD4(+) or CD8(+) T cell subpopulations. We show that TNF blockade acts directly on effector CD4(+) T cells, in the absence of monocytes or CD4(+) CD25(high)CD127(low) regulatory T cells and independently of IL-27, resulting in higher IL-10(+) frequencies after 3 days in culture. IL-10/IL-10R blockade reduced the frequency of IL-10-expressing cells both in the presence and absence of TNF blockade. Addition of recombinant IL-10 alone was insufficient to drive an increase in IL-10(+) CD4(+) T cell frequencies in 3-day CD4(+) T cell/monocyte cocultures, but resulted in increased IL-10 expression at later time points in whole PBMC cultures. Together, these data provide additional insights into the regulation of IL-10 expression in human T cells by TNF blockade. The maintenance of an IL-10(+) phenotype across a broad range of effector T cell subsets may represent an underappreciated mechanism of action underlying this widely used therapeutic strategy. url: https://doi.org/10.3389/fimmu.2017.00157 doi: 10.3389/fimmu.2017.00157 id: cord-006770-m5wqk6rh author: Rook, Graham A. W. title: Evaluation of TNF as antiviral, antibacterial and antiparasitic agent date: 1991 words: 4564.0 sentences: 212.0 pages: flesch: 43.0 cache: ./cache/cord-006770-m5wqk6rh.txt txt: ./txt/cord-006770-m5wqk6rh.txt summary: On the other hand such antibody had little effect if given on day 3 or later, suggesting that the protective role of TNF is mostly during the early phase of the infection. Effect of recombinant tumour necrosis factor on acute infection in mice with toxoplasma gondii or Trypanosoma cruzi Protective effects of tumor necrosis factor in experimental LegioneUa pneumophila infections of mice via activation of PMN function Production of tumor necrosis factor alpha and interteukin 1 beta by monocytic cells infected with human immunodeficiency virus The in vitro antiviral activity of tumor necrosis factor (TNF) in WISH cells is mediated by IFN-beta induction Human tumour necrosis factor alpha kills herpesvirus-infected, but not normal cells Cytocidal effect of tumor necrosis factor on cells chronically infected with human immunodeficiency virus (HIV): enhancement of HIV replication Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102365/ doi: 10.1007/bf02172089 id: cord-275413-e2rhioty author: Rowland, Raymond R.R. title: The interaction between PRRSV and the late gestation pig fetus date: 2010-09-09 words: 6183.0 sentences: 344.0 pages: flesch: 50.0 cache: ./cache/cord-275413-e2rhioty.txt txt: ./txt/cord-275413-e2rhioty.txt summary: The purpose of this study was to characterize the interaction between PRRSV and the pig fetus by (1) identifying sites of virus replication, (2) measuring immune and inflammatory cytokines in different compartments, and (3) evaluating the response of lymph nodes. Maternal, accessory and fetal tissues were collected and stored in formalin for histological staining and immunohistochemistry (IHC), or storage in RNAlater (Ambion) for RT-PCR of cytokine mRNAs. PRRSV-specific antibody was measured in sera using the HerdCheck ® PRRS ELISA (IDEXX) and performed by personnel at Kansas State University Veterinary Diagnostic Laboratory. As shown in Fig. 4A , IFN-␥ and TNF-␣ PCR products were not detected in lung, lymph node or placenta from the non-infected fetuses. To determine if cytokine gene expression was the direct result of PRRSV infection, RT-PCR for IFN-␥ and TNF-␣ was performed on the same tissues from fetuses of infected dam no. abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta during late gestation and productively infects the fetus. Virus replication and cytokine responses were measured in tissues of fetuses recovered at 109–112 days of gestation, just prior to parturition. At the time of recovery, gross anatomical abnormalities were evident in both infected and non-infected fetuses from the infected dams. Virus isolation and immunohistochemistry identified the thymus as the primary site of virus replication. Steady state RT-PCR amplification of inflammatory, Th1 and Th2 cytokines, showed elevated IFN-γ and TNF-α mRNAs in tissues from infected fetuses, which corresponded to elevated cytokine proteins in serum but not amniotic fluid. Further evidence for induction of immunity was found in the hyperplastic response of lymph nodes, which included the development of germinal centers occupied CDw75+ B cells. Collectively, these data support the notion that the immunocompetent fetus is capable of initiating an antiviral response, which is compartmentalized within the infected fetus. Furthermore, fetal pathology may not be a direct result of virus replication in the fetus. url: https://www.ncbi.nlm.nih.gov/pubmed/20832434/ doi: 10.1016/j.virusres.2010.09.001 id: cord-023429-x52gbklw author: Ruseva, M. title: Mannan‐Binding Lectin Inhibits Humoural Responses date: 2008-06-28 words: 16880.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023429-x52gbklw.txt txt: ./txt/cord-023429-x52gbklw.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Chronic hepatitis B virus (HBV) infection affects about 200–400 million people worldwide and represents one of the leading causes for liver cirrhosis and hepatocellular carcinoma. Control over the HBV infection is achieved mainly by vaccination with Hepatitis B surface antigen (HBsAg). HBsAg contains N‐linked glycosylation side and is recognized by both MBL‐A and MBL‐C in a Ca‐dependent manner. HbsAg–MBL complexes activate complement and may thus affect humoural immunity. To investigate the role of MBL in humoural responses to HBsAg, we immununized mice that lack both MBL‐A and MBL‐C proteins with soluble HBsAg. It has been shown that deficiencies in other complement components like C1q, C4 and C3 result in decreased antibody responses. However, MBL double KO animals mounted dramatically increased humoural responses. After priming, MBL double KOs mounted HbsAg‐specific IgM responses, which were threefold higher than WT controls. After boosting the HBsAg, total IgG was 10‐fold higher in MBL KO than in WT control animals. Similar to the response to HbsAg, other glycosylated soluble antigens (e.g. invertase) induced better humoural responses in MBL double KO animals, suggesting that MBL plays an important role in a negative feedback regulation of adaptive immunity. Reconstitution experiments with rMBL partially rescued the KO phenotype. We propose that the clearance of glycoprotein antigens in MBL KO is handled differently from the WT, resulting in better stimulation of humoural responses. Alternatively, glycoprotein‐Ag‐MBL‐rich complexes inhibit B‐cell responsiveness via putative MBL receptors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169581/ doi: 10.1111/j.0300-9475.2004.01423an.x id: cord-023425-3sjsogvq author: Røntved, C. M. title: Do High and Low Tumour Necrosis Factor‐α Responders Exist in Dairy Cows? date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A whole blood stimulation assay with Escherichia coli (O111:B4) endotoxin was established to measure the capacity of dairy cows to produce the proinflammatory cytokine tumour necrosis factor‐α (TNF‐α) ex vivo. Initially, a time‐ and dose‐dependent study was carried out to find the optimal stimulation conditions for the TNF‐α response. The TNF‐α response peaked between 3 and 4 h at 38.5 °C. A dose in the range of 5–10 g of E. coli lipopolysaccharide (LPS)/ml whole blood was found to give the maximum TNF‐α response. Thirty‐eight Danish–Holstein dairy cows were investigated for their TNF‐α responsiveness ex vivo in the periparturient period. Heparin‐stabilized blood samples were collected seven times over a period of 4 months (weeks −3, −1, 2, 3, 5, 9 and 13 around calving) and stimulated with 5 g/ml of E. coli LPS. Indeed, fluctuations in the TNF‐α responsiveness occurred over time. Moreover, the mean TNF‐α responsiveness of 38 cows was found to be significantly increased (P < 0.001) in the weeks close to calving. However, in the more stabile physiological periods, some cows had a consistently low TNF‐α response, whereas others had high a TNF‐α response. We are currently investigating whether high and low TNF‐α responders to E. coli LPS also exist in dairy cows in vivo. Moreover, the importance of TNF‐α responsiveness ex vivo to dairy cows' susceptibility and clinical response to experimental E. coli infections in the udder is being investigated. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169577/ doi: 10.1111/j.0300-9475.2004.01423v.x id: cord-020757-q4ivezyq author: Saikumar, Pothana title: Apoptosis and Cell Death: Relevance to Lung date: 2010-05-21 words: 7402.0 sentences: 420.0 pages: flesch: 39.0 cache: ./cache/cord-020757-q4ivezyq.txt txt: ./txt/cord-020757-q4ivezyq.txt summary: The extrinsic pathway involves binding of death ligands such as tumor necrosis factor-α (TNF-α), CD95 ligand (Fas ligand), and TNF-related apoptosis-inducing ligand (TRAIL) to their cognate cell surface receptors TNFR1, CD95/Fas, TRAIL-R1, TRAIL-R2, and the DR series of receptors, 29 resulting in the activation of initiator caspase-8 (also known as FADD-homologous ICE/CED-3-like protease or FLICE) and subsequent activation of effector caspase-3 ( Figure 4 .2). In cytotoxic T lymphocyte-induced death, granzyme B, which enters the cell through membrane channels formed by the protein perforin, activates caspases by cleaving them directly or indirectly. Intracellular Pathways: Lack of survival stimuli (withdrawal of growth factor, hypoxia, genotoxic substances, etc.) is thought to generate apoptotic signals through ill-defi ned mechanisms, which lead to translocation of proapoptotic proteins such as Bax to the outer mitochondrial membrane. For example, agents that damage DNA, such as ionizing radiation and certain xenobiotics, lead to activation of p53-mediated mechanisms that commit cells to apoptosis, at least in part through transcriptional upregulation of proapoptotic proteins. abstract: In multicellular organisms, cell death plays an important role in development, morphogenesis, control of cell numbers, and removal of infected, mutated, or damaged cells. The term apoptosis was first coined in 1972 by Kerr et al.1 to describe the morphologic features of a type of cell death that is distinct from necrosis and is today considered to represent programmed cell death. In fact, the evidence that a genetic program existed for physiologic cell death came from the developmental studies of the nematode Caenorhabditis elegans.2 As time has progressed, however, apoptotic cell death has been shown to occur in many cell types under a variety of physiologic and pathologic conditions. Cells dying by apoptosis exhibit several characteristic morphologic features that include cell shrinkage, nuclear condensation, membrane blebbing, nuclear and cellular fragmentation into membrane-bound apoptotic bodies, and eventual phagocytosis of the fragmented cell (Figure 4.1). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147438/ doi: 10.1007/978-0-387-72430-0_4 id: cord-313227-6zwkfzab author: Scala, Stefania title: Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs date: 2020-05-27 words: 3872.0 sentences: 202.0 pages: flesch: 36.0 cache: ./cache/cord-313227-6zwkfzab.txt txt: ./txt/cord-313227-6zwkfzab.txt summary: Interestingly, in patients infected by SARS-COv-2, there is an increase in IL1β, IFNγ, IP10, and MCP1, probably leading to activated T-helper-1 (TH1) cell responses, and increased production of T-helper-2 (TH2) immunosuppressive cytokines, such as IL4 and IL10 (18) . Peripheral blood examinations on admission in the majority of patients with COVID-19 displayed lymphopenia, elevated infection-related biomarkers (i.e., procalcitonin, erythrocyte sedimentation rate, serum ferritin, and C-reactive protein) (20) and several elevated inflammatory cytokines (i.e., tumor necrosis factor (TNF)-α, interleukin (IL)-2R and IL-6). Despite markedly reducing virus titers, anti-S-IgG caused lung injury during the early stages of infection, impairing the wound-healing macrophage response and TGF-β production, while promoting pro inflammatory cytokine IL-8, MCP1 production, and inflammatory macrophage accumulation (22) . Another proteasome inhibitor, VR23, possess powerful antiinflammatory activity reducing IL-6 in synovial cells from RA patients, and improving LPS-induced acute lung injury by decreasing neutrophil migration, TNF-α secretion, and tissue inflammation in a mice model (52) . abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15–20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the “pattern recognition receptors” (PRR) of the immune cells that release cytokines activating more immune cells that produce a large number of pro-inflammatory cytokines, tissue factors and vasoactive peptides. Affected patients might develop the “cytokine storm syndrome,” a fulminant and fatal hypercytokinaemia with multiorgan failure. In patients infected by SARS-COv-2 increase in T-helper 2 (TH2) cytokines (IL-4 and IL10) are reported in addition to the T-helper 1 (TH1) cytokines (IL1B, IFNγ, IP10, and MCP1) previously detected in other coronavirus infections. Cytokines and other molecules involved in immune response and inflammation are conceivable therapeutic targets for IP and ARDS, improving symptoms and decreasing intensive care unit admissions. To this aim off label drugs may be used taking into consideration the window timing for immunosuppressive drugs in virus infected patients. Some off label therapeutic options and preclinical evidence drugs are herein considered. url: https://www.ncbi.nlm.nih.gov/pubmed/32574268/ doi: 10.3389/fimmu.2020.01201 id: cord-023950-nv0pbbu2 author: Schnyder, Bruno title: Dual Role of Th17 Cytokines, IL-17A,F, and IL-22 in Allergic Asthma date: 2012-07-19 words: 4439.0 sentences: 245.0 pages: flesch: 41.0 cache: ./cache/cord-023950-nv0pbbu2.txt txt: ./txt/cord-023950-nv0pbbu2.txt summary: Unchecked activation of Th17 cells by IL-23 is linked to chronic inflammation in experimental autoimmune encephalomyelitis (EAE) and type II collagen-induced arthritis, two heretofore prototypical "Th1" disease models [6, 7] . Furthermore, Murdoch and Lloyd provide evidence in the model of acute allergen-induced response that the gdT cell-dependent normalization of lung function and resolution of inflammation was dependent on the production of IL-17 [16] . These data provide evidence that IL-17A,F and IL-22 besides their inflammatory role have a negative regulatory function in allergic lung inflammation. On a mechanistic level, IL-17A elicits dual effects and reportedly promotes expression of proinflammatory (hemopoietic, CXC-chemokines, acute phase) factors [54, 55] , whereas it inhibits the production of mononuclear cell recruiting molecules like TNF-induced VCAM-1 and CC-chemokine RANTES [35] . IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation abstract: The proinflammatory role of T helper (Th) 17 cells and therefore of its cytokines, IL-17 (IL-17A), IL-17F, and IL-22, in autoimmune disorders has been favored, although there is evidence that not only IL-17A but also IL-17F and IL-22 have a dual role as negative regulators. Here we review the concept of the dual function of IL-17A, IL-17F, and IL-22 in the light of recent strategies to use neutralization of these cytokines as potential alternative to neutralizing TNF and IL-1 treatments in chronic inflammatory disorders. Expectedly, in allergic lung inflammation, neutralization of IL-17A inhibited neutrophil recruitment. However, this IL-17A antibody treatment concomitantly increased eosinophil recruitment by neutralizing IL-17A’s dual role as negative regulator. IL-17A negatively regulated dendritic cell function and activation of T helper cell (Th)2 cytokine production. Furthermore, IL-17A inhibited Th2-characteristic chemokine and adhesion molecule expression. On a mechanistic level, IL-17A acted on IκB-β by preventing degradation and in turn leading to reduced NF-κB activation or IL-17A inhibited transcription factor IRF-1. Therefore, anti-IL-17A therapy, although presenting a promising lead in chronic inflammatory disorders, bears a potential risk of exacerbating allergic asthma. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178895/ doi: 10.1007/978-3-0348-0522-3_10 id: cord-023433-d1b7qvhs author: Siassi, M. title: Expression of Human Collectins in Colorectal Carcinoma date: 2008-06-28 words: 16906.0 sentences: 879.0 pages: flesch: 46.0 cache: ./cache/cord-023433-d1b7qvhs.txt txt: ./txt/cord-023433-d1b7qvhs.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Introduction: The human collectins, mannan‐binding lectin (MBL), surfactant protein‐A (SP‐A) and surfactant‐protein‐D (SP‐D) play a central role in the innate immune system. Immunological responses to malignant transformation of epithelial cells gained increasing interest recently. A former study could demonstrate binding of MBL to certain colorectal carcinoma (CRC) cell lines in vitro. We therefore examined the expression of human collectins in normal colon mucosa and in colorectal carcinomas. Materials and methods: Colon samples from 20 CRC patients and 10 normal mucosa samples were collected immediately after surgery. The tissue was microdissected and RNA isolated (Qiagen, Rneasy‐Kit). Gene expression profiles were analysed using Gene‐chips (Affymetrix, HG‐U133). We analysed the data for the expression of MBL, its associated serine proteases mannan‐binding lectin‐associated serine protease 1/2 (MASP 1/2), SP‐A and SP‐D. The signal intensity of the genes of interest was compared using the Mann–Whitney U‐test. Results: The expression of human collectins in normal human colon mucosa was generally low. Only the expression of SP‐A and MASP‐2 reached the noise threshold of 250 signals. These genes were significantly downregulated in CRC specimens. The expression of the other proteins showed no difference in normal mucosa and CRC. Conclusion: As demonstrated before, the expression of human collectins in normal colon was low in this study. Only SP‐A showed a significant expression in normal mucosa which was downregulated in CRC. As the absolute signal level was below the noise threshold, these results have to be interpreted with caution and require confirmation by direct measurenment of the proteins. Our results suggest that there is no major role for the human collectins in colorectal cancer. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169588/ doi: 10.1111/j.0300-9475.2004.01423bo.x id: cord-023431-zjyrhlxn author: Sigmundsdóttir, H. title: Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells date: 2008-06-28 words: 16867.0 sentences: 869.0 pages: flesch: 46.0 cache: ./cache/cord-023431-zjyrhlxn.txt txt: ./txt/cord-023431-zjyrhlxn.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: The interaction with adhesion molecules expressed by vascular endothelium is the first step in lymphocyte infiltration into tissues. At both cutaneous and mucosal sites interleukin‐10 (IL‐10), IL‐12 and transforming growth factor (TGF)‐β are important regulators of chronic inflammatory disease, where cutaneous lymphocyte‐associated antigen (CLA) and αE integrin (CD103) may be expressed. Unlike CLA, CD103 is not believed to play a role in tissue‐specific homing but may help to retain T cells within epithelial layers. We have previously shown that IL‐12 alone can together with an unknown cofactor increase the expression of CLA. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8(+) but not CD4(+) T cells. While IL‐12 increased superantigen‐stimulated expression of CLA, this cytokine strongly inhibited the CD103 expression, and a combination of IL‐12 and TGF‐β completely abrogated the induced CD103 expression. Conversely, IL‐10 suppressed CLA but increased CD103 expression. These findings indicate that, in addition to suppressing the development of Th1‐mediated inflammatory responses, IL‐10 may also inhibit the migration of CD8(+) T cells into the skin while IL‐12 promotes such migration. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL‐10 and IL‐12, and the balance between these cytokines could influence the T‐cell migration of inflammatory cells into epithelial tissues. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169583/ doi: 10.1111/j.0300-9475.2004.01423ab.x id: cord-256837-100ir651 author: Smith, Steven B. title: Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date: 2012-03-14 words: 8447.0 sentences: 415.0 pages: flesch: 38.0 cache: ./cache/cord-256837-100ir651.txt txt: ./txt/cord-256837-100ir651.txt summary: Several recent studies have generated multiple mRNA microarray gene expression datasets derived from experiments involving the infection of human cell-lines or animal models with one or more of the major respiratory viruses [21] [22] [23] . Through a systematic analysis of these respiratory virus-human host gene expression datasets, we determined common sets of genes and pathways involved in host responses to viral infections. A total of seven different respiratory viruses were analyzed, represented by fifteen unique Gene Expression Omnibus (GEO) datasets (indicated by GEO Series or GSE accession numbers), nine different human cell types, and seven different array platforms for a total of 28 unique comparisons. This assumption is based on the occurrence of genes that are differentially expressed in infection models for at least five of the seven respiratory viruses, have involvement in a number of relevant pathways related to host immune response, and encode for known drug targets. abstract: BACKGROUND: Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses invoke several common host response pathways. Further analysis of these pathways suggests potential opportunities for therapeutic intervention. url: https://doi.org/10.1371/journal.pone.0033174 doi: 10.1371/journal.pone.0033174 id: cord-323553-bukm9m9q author: Song, Woo-Jin title: Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice date: 2019-08-31 words: 4238.0 sentences: 256.0 pages: flesch: 52.0 cache: ./cache/cord-323553-bukm9m9q.txt txt: ./txt/cord-323553-bukm9m9q.txt summary: title: Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice Mesenchymal stem cells (MSCs), which release immunomodulatory factors such as tumor necrosis factor-α (TNF-α)-induced gene/protein 6 (TSG-6) and prostaglandin E2 (PGE2), have been suggested as an alternative therapeutic option for IBD treatment in veterinary medicine. (C) Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α released higher concentrations of immunomodulatory factors such as TSG-6 and PGE2 compared to levels released by naive cAT-MSCs. Results are shown as the mean ± standard deviation of three independent experiments. Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α showed enhanced therapeutic effects on mice with dextran sodium sulfate (DSS)-induced colitis. Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α showed enhanced therapeutic effects on mice with dinitrobenzene sulfonic acid (DNBS)-induced colitis. abstract: Abstract Canine inflammatory bowel disease (IBD) is an intractable autoimmune disorder that results in various gastrointestinal and systemic symptoms. Mesenchymal stem cells (MSCs), which release immunomodulatory factors such as tumor necrosis factor-α (TNF-α)-induced gene/protein 6 (TSG-6) and prostaglandin E2 (PGE2), have been suggested as an alternative therapeutic option for IBD treatment in veterinary medicine. Furthermore, although it is known that MSCs pre-treated with pro-inflammatory cytokines show enhanced anti-inflammatory properties via the secretion of soluble factors, the underlying mechanisms of IBD remain unclear. The aim of this study was to demonstrate the therapeutic effects and corresponding mechanisms of canine adipose tissue-derived (cAT)-MSCs stimulated with TNF-α in mouse models of IBD. Mice with dextran sulfate sodium (DSS)- or dinitrobenzene sulfonic acid (DNBS)-induced colitis were injected intraperitoneally with cAT-MSCs pre-treated with TNF-α. Colitis severity was assessed and colon tissues were collected for histopathological, enzyme-linked immunosorbent assay, and flow cytometry analysis. cAT-MSCs stimulated with TNF-α secreted higher concentrations of immunomodulatory factors such as TSG-6 and PGE2, which play a key role in inducing phenotypic alterations in macrophages. Consequently, TNF-α-pre-treated cAT-MSCs further regulated colonic inflammatory cytokines such as interleukin (IL)-1β, IL-6, and IL-10, and ameliorated DSS- or DNBS-induced colitis in mice. Additionally, we demonstrated that M1 macrophages (F4/80+/iNOS+ cells) were decreased in colon tissues from mice treated with TNF-α-pre-treated cAT-MSCs, whereas M2 macrophages (F4/80+/CD206+ cells) were increased. These results may suggest a new cell-based therapeutic option for treating IBD. url: https://doi.org/10.1016/j.rvsc.2019.06.012 doi: 10.1016/j.rvsc.2019.06.012 id: cord-000324-to4g9he9 author: Spentzas, Thomas title: Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus date: 2011-01-25 words: 5297.0 sentences: 245.0 pages: flesch: 37.0 cache: ./cache/cord-000324-to4g9he9.txt txt: ./txt/cord-000324-to4g9he9.txt summary: title: Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus In a sepsis simulation model, we tested whether the anesthetic ketamine inhibits the macrophage TNF response to antibiotic-exposed CA-MRSA bacteria via its antagonism of N-methyl-D-aspartate (NMDA) receptors. The NMDA inhibitors, MK-801 and APV, also suppressed macrophage TNF secretion after stimulation with either of the antibiotic-exposed CA-MRSA isolates, and the effect was not additive or synergistic with ketamine. The mechanisms responsible for the anti-inflammatory effects of ketamine are not known [22] [23] [24] [25] .The present study examined the hypothesis that ketamine could suppress macrophage TNF production in response to whole bacteria, in this case clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). The addition of ketamine (100 μΜ) to macrophage cell cultures inhibited TNF secretion in response to vancomycin-or daptomycin-exposed CA-MRSA isolates ( Figure 2) . abstract: BACKGROUND: Infections caused by community-associated strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) are associated with a marked and prolonged host inflammatory response. In a sepsis simulation model, we tested whether the anesthetic ketamine inhibits the macrophage TNF response to antibiotic-exposed CA-MRSA bacteria via its antagonism of N-methyl-D-aspartate (NMDA) receptors. RAW264.7 cells were stimulated for 18 hrs with 10(5 )to 10(7 )CFU/mL inocula of either of two prototypical CA-MRSA isolates, USA300 strain LAC and USA400 strain MW2, in the presence of either vancomycin or daptomycin. One hour before bacterial stimulation, ketamine was added with or without MK-801 (dizocilpine, a chemically unrelated non-competitive NMDA receptor antagonist), APV (D-2-amino-5-phosphono-valerate, a competitive NMDA receptor antagonist), NMDA, or combinations of these agents. Supernatants were collected and assayed for TNF concentration by ELISA. RESULTS: RAW264.7 cells exposed to either LAC or MW2 in the presence of daptomycin secreted less TNF than in the presence of vancomycin. The addition of ketamine inhibited macrophage TNF secretion after stimulation with either of the CA-MRSA isolates (LAC, MW2) in the presence of either antibiotic. The NMDA inhibitors, MK-801 and APV, also suppressed macrophage TNF secretion after stimulation with either of the antibiotic-exposed CA-MRSA isolates, and the effect was not additive or synergistic with ketamine. The addition of NMDA substrate augmented TNF secretion in response to the CA-MRSA bacteria, and the addition of APV suppressed the effect of NMDA in a dose-dependent fashion. CONCLUSIONS: Ketamine inhibits TNF secretion by MRSA-stimulated RAW264.7 macrophages and the mechanism likely involves NMDA receptor antagonism. These findings may have therapeutic significance in MRSA sepsis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037927/ doi: 10.1186/1471-2172-12-11 id: cord-023419-lnmc6vv5 author: Steinhauer, C. title: High‐Throughput Proteomics on Antibody‐based Microarrays: the Importance of Probe and Surface Design date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In analogy to DNA microarrays, protein microarrays offer a new distinct possibility to perform sensitive high‐throughput global proteome analysis. However, the development of the protein microarray technology will place high demands upon the design of both probes and solid supports. The analysis of thousands of heterogeneous proteins on a single microarray requires the use of uniform probes, such as antibodies, directly designed for protein microarray applications. We have recently generated a human recombinant single‐chain Fv antibody library, genetically constructed around one framework, the nCoDeR‐library, containing 2 × 1010 clones. Single framework antibody fragments (sinFabs) selected from this library were successfully applied as probes for microarrays providing sensitive detection in the 600 attomol (mass spectrometry) and the 300 zeptomole range (fluorescence). However, the choice of framework is critical. We have shown that the selected nCoDeR framework displayed excellent functional on‐chip stability and arrayed dehydrated probes retained their activity for several months. Furthermore, we have addressed the issues of biocompatibility of the solid support and immobilization strategies for our microarray setup. An in‐house‐designed substrate, macroporous silicon coated with nitrocellulose (MAP3‐NC7), displayed properties equal to, or better than, those of five commercially available supports used as reference surfaces. We have also evaluated different coupling strategies, such as adsorption, covalent coupling, diffusion and affinity coupling. Using a novel affinity tag, the double‐(his)6‐tag, we increased the binding efficiency of sinFab‐molecules to Ni2(+)‐coated solid supports, thereby allowing nonpurified probes to be directly applied. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169563/ doi: 10.1111/j.0300-9475.2004.01423ax.x id: cord-023374-87ob1exq author: Sukhija, S. title: Levels, Complement Activity and Polymorphisms of Mannan‐Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis date: 2008-06-28 words: 16891.0 sentences: 869.0 pages: flesch: 46.0 cache: ./cache/cord-023374-87ob1exq.txt txt: ./txt/cord-023374-87ob1exq.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Activation of complement pathways, leading to production of C3a and C5a anaphylatoxins, has been postulated in the pathogenesis of asthma and allergic airway inflammation. The present study was undertaken to investigate the role of mannan‐binding lectin (MBL), an initiator of the lectin pathway of complement, in asthma and allergic rhinitis. MBL levels and MBL‐induced complement activity were determined in 19 patients of bronchial asthma with allergic rhinitis and 20 unrelated, age‐matched controls of Indian origin. MBL levels and activity were correlated with percent eosinophilia and percent predicted FEV1 values of the patients. Association of single nucleotide polymorphisms (SNPs) in exon 1 and intron 1 of the MBL with the disease, clinical markers, MBL levels and MBL‐induced complement activity was analysed using standard statistical tools. Significantly higher MBL levels and activity were observed in patients of bronchial asthma with allergic rhinitis as compared to the controls. We identified five SNPs, of which two, A816G in exon 1 and G1011A in intron 1 of the MBL, were novel. SNP G1011A was significantly associated with the disease (P = 0.0024, OR = 5.8696, 95% CI: 1.7316 < OR < 19.8963). Individuals with ‘A’ allele at position 1011 showed increased MBL levels, activity and disease severity. Our results suggest that ‘A’ allele at position 1011 leading to high MBL levels and complement activity may be contributing to the severity of bronchial asthma and allergic airway inflammation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169489/ doi: 10.1111/j.0300-9475.2004.01423ai.x id: cord-279498-ez3yq7xi author: Suzumura, Akio title: Immune Response in the Brain: Glial Response and Cytokine Production date: 2008-12-31 words: 5319.0 sentences: 308.0 pages: flesch: 45.0 cache: ./cache/cord-279498-ez3yq7xi.txt txt: ./txt/cord-279498-ez3yq7xi.txt summary: Cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-3 induce class I major histocompatibility complex (MHC) antigen expression on neural cells. In the brains of experimental allergic encephalomyelitis (EAE), microglia near the infiltrating T cells are reported to be class II MHC antigen-positive [6] [7] [8] , suggesting that a T cell-derived cytokine, most probably IFN-g, can induce class II MHC antigen expression in vivo as well. Since the BBB is not damaged in this experimental condition and since there is no definitive evidence that neural cells produce INF-g in the CNS, it is unlikely that IFN-g is responsible for the induction of class II MHC antigen expression in this model. In contrast to IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) downregulates IFN-g-induced class II MHC antigen expression in microglia. IL-10 suppresses cytokine production and IFN-g-induced class II MHC antigen expression in microglia, but does not suppress the proliferation or the activation of lysosomal enzymes in microglia [18] . abstract: Abstract Although the brain has been considered as an immunologically privileged site, the evidence to date suggests that this is no longer the case. Cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-3 induce class I major histocompatibility complex (MHC) antigen expression on neural cells. IFN-γ, the most potent inducer of MHC antigen, also induces class II MHC antigen expression on microglia and astrocytes, which enable them to function as antigen-presenting cells. Thus, in some pathological conditions, invading T cells can interact with neural cells to induce central nervous system (CNS) damage. Glial cells have also been shown to produce various cytokines and chemokines. Almost all cytokines and chemokines known to occur in the immune system are also produced in the CNS. In this chapter, the glial responses contributing to neuroimmune interactions are reviewed, with a focus on production and functions of cytokines in the CNS. url: https://api.elsevier.com/content/article/pii/S1567744307100144 doi: 10.1016/s1567-7443(07)10014-4 id: cord-023421-1d1gf7az author: Sønder, S. U. S. title: Monitoring Patients Treated with Type 1 Interferons: Antiviral versus MxA Induction Assays date: 2008-06-28 words: 16866.0 sentences: 873.0 pages: flesch: 46.0 cache: ./cache/cord-023421-1d1gf7az.txt txt: ./txt/cord-023421-1d1gf7az.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Interferon‐α/β (IFN‐α/β) is increasingly used as antiviral and immunomodulatory therapies. Unfortunately, bioavailability varies with IFN species and mode of administration, and all IFN species are potentially immunogenic. Assays for antiviral activity (IFN) and antiviral neutralization (antibodies, NAb) have been used for some time to monitor patients on IFN biologicals. These assays require laborious titrations making them unsuitable for large‐scale clinical use. Our laboratories have therefore modified the antiviral assays for IFN bioactivity and Nab, so that they are suitable for large‐scale screening in specialized laboratories. The read‐out is survival of a subcloned A549 cell line in the presence of an otherwise lethal amount of virus. Thus, survival increases in the presence of type 1 IFN and decreases in the presence of NAb against the IFN added to the cells. MxA is induced by type 1 IFN and can be used for measuring the Nab activity. In another assay, the MxA level in the A549 cell line is measured. In an attempt to find a new and better reporter gene for type 1 IFN than MxA and genes specific for either IFN‐α or ‐β, a micro array screen was carried using the U133A chip from Affymetrix. The expression of 22,000 genes can be studied simultaneous with this technology. The results will be presented at the conference. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169566/ doi: 10.1111/j.0300-9475.2004.01423bb.x id: cord-353887-f4yd7guj author: Tang, Yujun title: Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies date: 2020-07-10 words: 8532.0 sentences: 461.0 pages: flesch: 44.0 cache: ./cache/cord-353887-f4yd7guj.txt txt: ./txt/cord-353887-f4yd7guj.txt summary: Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients. In this review, we referred COVID-19 associated cytokine storm as the patients who are severely ill along with a high concentration of pro-inflammatory cytokines. The innate and adaptive immune responses activated by SARS-CoV-2 infection lead to uncontrolled inflammatory responses and ultimately cause the cytokine storm (14) . MERS-CoV infects the cells mentioned above to induce delayed (but increased) levels of pro-inflammatory cytokines (e.g., IL-2) and chemokines (e.g., CCL2, CCL3) (27, 30) . Although SARS-CoV is abortive in macrophages and DCs, the virus induces an increase in levels of pro-inflammatory cytokines and chemokines (31, 32) . A comment and a meta-analysis, which mainly bases on the evidence of SARS and MERS (64, 65) , stated that corticosteroid would increase mortality and delayed clearance of viral in coronavirus infection diseases. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the “cytokine storm” may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients. url: https://doi.org/10.3389/fimmu.2020.01708 doi: 10.3389/fimmu.2020.01708 id: cord-023928-9a1w174h author: Thomas, Neal J. title: Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date: 2011-12-16 words: 12255.0 sentences: 510.0 pages: flesch: 46.0 cache: ./cache/cord-023928-9a1w174h.txt txt: ./txt/cord-023928-9a1w174h.txt summary: authors: Thomas, Neal J.; Dahmer, Mary K.; Quasney, Michael W. Examples of the infl uence of genetic variations in proteins involved in recognition of pathogens on the severity of infections include polymorphisms in the genes coding for mannose binding Individual variability in the susceptibility to and outcome from critical care diseases has long been observed, and advances in genomic medicine now gives an opportunity to understand these differences. abstract: Much progress has been made in the past decade in the understanding of the genetic contribution to the development of human disease in general, and critical care illness specifically. With the mapping of the human genome and on-going mapping of genetic polymorphisms and haplotypes in humans, the field of critical care is now in prime position to study the impact of genetics on common illnesses that affect children who require critical care, to examine how differences of the host defense response lead to variable outcomes in outwardly appearing similar disease states, and to study how genetic differences in response to therapy will help practitioners tailor therapeutic interventions to an individual child’s genetic composition. While we are still years away from true individualized medicine, we are now closer than ever to understanding why two might children respond to the same environmental insult in vastly different ways. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178837/ doi: 10.1007/978-0-85729-923-9_11 id: cord-023391-bq5w3jk9 author: Utermöhlen, O. title: Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes date: 2008-06-28 words: 16856.0 sentences: 870.0 pages: flesch: 46.0 cache: ./cache/cord-023391-bq5w3jk9.txt txt: ./txt/cord-023391-bq5w3jk9.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: The phagolysosomally localized acid sphingomyelinase (ASMase) activated by proinflammatory cytokines such as TNF and IFN‐γ generates the signalling molecule ceramide which in turn results in the activation of proteases like cathepsin D. These characteristics of ASMase suggest a possible role of this molecule in the phagocytotic uptake and phagosomal degradation processes of antigens or in antigen presentation. We show here that ASMase(–/–) mice fail to eliminate the noncytopathic lymphocytic choriomeningitis (LCM) virus as rapidly as littermate wildtype mice. Investigation of the immune response revealed a reduced expansion of CD8(+) T cells. The secretion of IFN‐γ in response to contact with target cells as well as the cytolytic activity of virus‐specific CD8(+) T cells was severely impaired. Additionally, both phases of the LCM virus‐specific DTH response, mediated by CD8(+) and CD4(+) T cells consecutively, were diminished in ASMase(–/–) mice. However, the secondary memory response of virus‐specific CTL was not altered, and the virus was effectively controlled for at least 3 months by ASMase(–/–) mice. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus‐specific CD8(+) T cells during the acute infection of mice with the LCM virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169516/ doi: 10.1111/j.0300-9475.2004.01423l.x id: cord-259586-kep2dgaw author: Van Reeth, Kristien title: In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding date: 2002-09-10 words: 4193.0 sentences: 231.0 pages: flesch: 49.0 cache: ./cache/cord-259586-kep2dgaw.txt txt: ./txt/cord-259586-kep2dgaw.txt summary: This review concentrates on in vivo studies of cytokine involvement in infectious respiratory diseases of swine, with an emphasis on viral infections. In the authors'' laboratory, studies were undertaken to investigate the relationship between viral respiratory disease and bioactive lung lavage levels of IFN-α, TNF-α, IL-1 and IL-6. We have previously demonstrated different cytokine pro-®les in BAL¯uids of gnotobiotic pigs infected with porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) or swine in¯uenza virus (SIV) (Van Reeth et al., 1999) . In an attempt to study interactions between respiratory viruses and secondary agents in a reproducible way, we have performed subsequent inoculations of pigs with either PRCV or PRRSV followed by bacterial lipopolysaccharide (LPS). Prior infection with PRCV truly potentiated the cytokine response to LPS, with 10±100 times higher titres of TNF-a, IL-1 and IL-6 than after the respective single inoculations. Differential production of proin¯ammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity abstract: The early cytokines interferon-α (IFN-α), tumour necrosis factor-α (TNF-α), interleukin-1, -6 and -8 (IL-1, -6, -8) are produced during the most early stage of an infection. The activities of these cytokines have been studied extensively in vitro and in rodents, but in vivo studies on the role of these cytokines in infectious diseases of food animals are few. This review concentrates on in vivo studies of cytokine involvement in infectious respiratory diseases of swine, with an emphasis on viral infections. First evidence for the role of early cytokines in pneumonia in swine came from experimental infections with Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. The role of TNF-α and IL-1 in the symptoms and pathology of porcine pleuropneumonia has recently been proven by use of an adenovirus vector expressing the anti-inflammatory IL-10. In the authors’ laboratory, studies were undertaken to investigate the relationship between viral respiratory disease and bioactive lung lavage levels of IFN-α, TNF-α, IL-1 and IL-6. Out of three respiratory viruses—porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV)—only SIV induced acute respiratory disease and severe lung damage by itself. Disease and lung pathology were tightly associated with the simultaneous production of IFN-α, TNF-α, IL-1 and IL-6. In challenge studies of SIV-vaccinated pigs, levels of IFN-α, TNF-α and IL-6, but not IL-1 were correlated with clinical and virological protection. Multifactorial respiratory disease was reproduced by combined inoculations with PRCV or PRRSV followed by LPS from Escherichia coli. In comparison with the respective single inoculations, which were subclinical, there was a true potentiation of disease and production of TNF-α, IL-1 and IL-6. TNF-α and IL-6 were best correlated with disease. In further studies, we will use more specific strategies to dissect the role of cytokines during viral infections. url: https://api.elsevier.com/content/article/pii/S0165242702000478 doi: 10.1016/s0165-2427(02)00047-8 id: cord-341667-ayl71jpc author: Van Reeth, Kristien title: Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans? date: 1998-04-17 words: 1959.0 sentences: 121.0 pages: flesch: 48.0 cache: ./cache/cord-341667-ayl71jpc.txt txt: ./txt/cord-341667-ayl71jpc.txt summary: Biologically active interferon-a, tumor necrosis factor-a (TNF-a), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Biologically active interferon-a, tumor necrosis factor-a (TNF-a), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Levels of the three cytokines were significantly higher 18 -24 h after inoculation than at 48 -72 h after inoculation (P õ Clinical responses, influenza virus titers, BAL cell numbers, percentage of neutrophils, and cytokine titers of individual pigs .016 for all three cytokines). On histopathology, bronchi/bronchioli and, to a lesser degree, alveoli showed epithelial necrosis and To our knowledge, this is the first demonstration of influenza virus -induced TNF-a and IL-1 in BAL fluids of a natural virus massive neutrophil infiltration at 18 -24 h after inoculation. abstract: Biologically active interferon-α, tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Cytokine titers and lung virus titers were significantly higher 18–24 h after inoculation than at 48–72 h after inoculation in all 4 litters of pigs examined. All three cytokines were positively correlated with a 3- to 4-fold increase in BAL cell numbers (P < .036) and with a drastic neutrophil infiltration (24%–77% of BAL cells vs. 0–1.5% in controls) (P < .001). In addition, cytokine production coincided with the onset of general and respiratory symptoms of influenza and with the development of a necrotizing bronchopneumonia. This study is the first demonstration of TNF-α and IL-1 in BAL fluids of a natural influenza virus host. It documents that pigs may be a highly valuable experimental model in human influenza virus pneumonia. url: https://www.ncbi.nlm.nih.gov/pubmed/9534986/ doi: 10.1086/517398 id: cord-007621-rapinodd author: Vidovic, Maria title: Induction and regulation of class II major histocompatibility complex mRNA expression in astrocytes by interferon-γ and tumor necrosis factor-α date: 2002-11-13 words: 6680.0 sentences: 365.0 pages: flesch: 57.0 cache: ./cache/cord-007621-rapinodd.txt txt: ./txt/cord-007621-rapinodd.txt summary: Previous data from this laboratory had shown that the cytokine tumor necrosis factor-α (TNF-α) enhances IFN-γ-mediated class II antigen expression on astrocytes. To determine the steady-state level of mRNA for class II, Northern blot analysis was performed using a eDNA probe for murine class Ii genes (E-a), with total RNA isolated from cultured astrocytes. The duration of protein synthesis required to allow expression of the class II MHC gene in astrocytes was examined in cells that were pretreated with IFN-y or IFN-7/TNF-a for different lengths of time prior to the addition of CHX. In this study we have shown that primary neonatal rat astrocytes, upon stimulation with IFN-~,, express mRNA transcripts for class II MHC genes, and that TNF-a enhances the expression of IFN-~,-induced class II mRNA. The expression of class II mRNA was completely inhibited when CHX was included with IFN-~, and IFN-''t/TNF-~ treatment, indicating that newly synthesized protein is required for astrocyte class II MHC gene expression. abstract: Astrocytes can function as antigen-presenting cells (APC) upon expression of class II major histocompatibility complex (MHC) antigens, which are induced by interferon-γ (IFN-γ). Previous data from this laboratory had shown that the cytokine tumor necrosis factor-α (TNF-α) enhances IFN-γ-mediated class II antigen expression on astrocytes. We have now investigated the effect of IFN-γ and TNF-α on class II MHC mRNA expression in astrocytes using Northern blot analysis. Astrocytes do not constitutively express mRNA for class II MHC. Kinetic analysis of class II MHC mRNA expression in IFN-γ-treated cells demonstrated an 8 h time lag, which was followed by an increase over the next 16 h. Optimal expression of class II mRNA was detected after a 24 h incubation with IFN-γ. This level of expression was further enhanced by the simultaneous addition of IFN-γ and TNF-α to the astrocytes, while TNF-α alone had no effect on class II mRNA expression. TNF-α does not act by increasing the stability of IFN-γ-induced class II mRNA, indicating its action is not at that specific level of post-transcriptional control. Furthermore, astrocyte class II mRNA expression was inhibited when cycloheximide (CHX) was added together with IFN-γ or IFN-γ/TNF-α, and when CHX was added up to 4 h after treatment with IFN-γ or IFN-γ/TNF-α. These results indicate that astrocyte class II mRNA expression is mediated by newly synthesized proteins induced by IFN-γ and/or IFN-γ/TNF-α. The expression of class II antigens on astrocytes, and cytokine modulation of their expression, may be important in the initiation and perpetuation of intracerebral immune responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119667/ doi: 10.1016/0165-5728(90)90103-t id: cord-023417-by18aczt author: Vilhelmsson, M. title: The Malassezia sympodialis Allergen Mala s 11 with Sequence Similarity to Manganese Superoxide Dismutase Induces Maturation and Production of Inflammatory Cytokines in Human Dendritic Cells date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The chronic inflammatory skin disease atopic eczema (AE) affects almost 15% of the population in many countries today. The pathogenesis of AE is not fully understood. A combination of genetic predisposition and environmental factors like microorganisms seems to contribute to the symptoms. The yeast Malassezia sympodialis is part of our normal skin micro flora but can act as an allergen and elicit specific IgE and T‐cell reactivity in patients with AE. Recently, we identified a novel major M. sympodialis allergen, designated Mala s 11 (22.4 kDa), with sequence similarity to the mitochondrial enzyme manganese superoxide dismutase (MnSOD). Interestingly, Mala s 11 has a high degree of homology to human MnSOD. The aim of this study was to examine the effects of recombinant Mala s 11 on antigen‐presenting dendritic cells. Monocyte‐derived dendritic cells (MDDCs) from healthy blood donors were cultured with or without Mala s 11 for different time periods. It was found that the maturation marker CD83 and the costimulatory molecules CD80 and CD86 were upregulated on the MDDCs exposed to Mala s 11 for 24 h, as demonstrated by flow cytometry. Furthermore, coculture of MDDCs with Mala s 11 for 9 h induced an increased production of the inflammatory cytokines IL‐6 (200‐fold), TNF‐α (100‐fold) and IL‐8 (sixfold), as detected by the cytometric bead array (CBA) analysis. Our results suggest that Mala s 11 affects the immune response through DC maturation and production of inflammatory cytokines. The potential cross‐reactivity with human MnSOD needs to be explored and the exact role of Mala s 11 in the pathogenesis of AE assessed in clinical studies involving skin prick and atopy patch tests. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169559/ doi: 10.1111/j.0300-9475.2004.01423ae.x id: cord-005872-w1x1i0im author: Volk, T. title: Endothelium function in sepsis date: 2000 words: 8871.0 sentences: 463.0 pages: flesch: 29.0 cache: ./cache/cord-005872-w1x1i0im.txt txt: ./txt/cord-005872-w1x1i0im.txt summary: Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. S. aureus has been reported to directly infect human umbilical vein endothelial cells (HUVEC) thereby inducing secretion of cytokines and functional upregulation of adhesion molecules [2] . Infection and activation of endothelial cells by Listeria monocytogenes is believed to be a critical component of the pathogenesis of this disease and includes ceramide generation, transcription factor activation and increases in adhesion molecule expression on HUVEC [11] . E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation abstract: Endothelial cells can be the prime target for an infection and infected endothelial cells may serve as an initiating system for a systemic response as these cells are able to secrete many mediators known to be of paramount importance. Endothelial cell functions in turn are regulated by these circulating mediators. Cellular interactions with leukocytes revealed protective and destructive functions. Single cell and animal studies indicate that endothelial permeability is increased and apart from clinical obvious edema formation in septic patients, the endothelial component remains unknown. Endothelial coagulation activation has been shown in vitro, however human data supporting an endothelial procoagulatory state are lacking. Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095878/ doi: 10.1007/s000110050579 id: cord-022353-q2k2krnm author: W. Quimby, Fred title: Clinical Chemistry of the Laboratory Mouse date: 2007-09-02 words: 30195.0 sentences: 1702.0 pages: flesch: 48.0 cache: ./cache/cord-022353-q2k2krnm.txt txt: ./txt/cord-022353-q2k2krnm.txt summary: Assessment of long-term average blood glucose levels in mice is also available by RIAs measuring glycosylated hemoglobin and glycosylated serum proteins (collectively known as fructosamines) (Gould et al. Leptin resistance, a common feature of obesity in mice and humans, has also been shown to result, in part, from the shedding of membrane-bound hepatic leptin receptors into the plasma, where soluble receptors modulate circulating leptin levels and possibly its biologic activity (Cohen et al. d. OTHER ANALYTES ASSOCIATED WITH LIPID METABOLISM AND ATHEROSCLEROSIS IN MICE ELISA kits are commercially available for the quantitation of many mouse coagulation proteins including: fibrinogen, factor VII, d-dimer, tissue factor, and von Willebrand''s factor antigen. The ability of the first component of complement, C1, to bind specific sites on the heavy chain of mouse IgG2b and activate a sequence of reactions leading to production of a molecular unit capable of lysing a target cell membrane has established the complement system as the primary mediator of antibody-antigen reactions. abstract: The frontier of clinical chemistry in the mouse has advanced and expanded because of two major events such as, the increasing reliance on mice in biomedical research, and increasing availability of practical yet sophisticated techniques and instrumentations that have allowed for the detection of a wider variety of biomarkers of disease. The progression of these two events is partially driven by the increasing regulatory demands related to safety/toxicity assessment of novel drug development. The availability of inbred strains has led to major breakthroughs in cancer, biology, and immunology. In addition, outbred stocks continue to be utilized in a wide variety of studies but particularly in the fields of toxicology and pharmacology. The power of these models to elucidate the genetic basis of disease cannot be overemphasized. This provided complete nucleotide sequences for each genome allowing investigators to quickly develop the equivalent murine model for many of the inherited human diseases. Transgenic and knockout mice have helped clarify disease pathogenesis in virtually every area of medicine and often elucidated biochemical pathways, previously unknown, which are now subject to testing and quantification. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155603/ doi: 10.1016/b978-012369454-6/50060-1 id: cord-291076-p350i54m author: Wang, Renxi title: The role of C5a in acute lung injury induced by highly pathogenic viral infections date: 2015-05-06 words: 5790.0 sentences: 373.0 pages: flesch: 42.0 cache: ./cache/cord-291076-p350i54m.txt txt: ./txt/cord-291076-p350i54m.txt summary: Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. [1] [2] [3] In addition, the complement system has been implicated in the development of acute lung diseases induced by highly pathogenic viruses including influenza A virus H1N1, 4 H5N1, 5 H7N9, 6 severe acute respiratory syndrome coronavirus (SARS-Cov), 7 Middle East respiratory syndrome coronavirus (MERS-Cov). C5a-mediated release of reactive oxygen species C5a is a strong chemoattractant for neutrophils and monocytes; it then activates these cells to generate oxidative burst with release of 10 A study demonstrated that ROS are primary pathogenic molecules in pneumonia from mice infected with influenza virus. Inhibition of Complement Activation Alleviates Acute Lung Injury Induced by Highly Pathogenic Avian Influenza H5N1 Virus Infection abstract: The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named “cytokine storm”, and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses. url: https://doi.org/10.1038/emi.2015.28 doi: 10.1038/emi.2015.28 id: cord-346669-7n75m669 author: Wang, Shixin title: Roles of TNF-α gene polymorphisms in the occurrence and progress of SARS-Cov infection: A case-control study date: 2008-02-29 words: 3814.0 sentences: 200.0 pages: flesch: 53.0 cache: ./cache/cord-346669-7n75m669.txt txt: ./txt/cord-346669-7n75m669.txt summary: This study was to investigate the relationship between tumor necrosis factor (TNF)-α gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. METHODS: The association between genetic polymorphisms of TNF-α gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-α gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. In this paper, we aimed to study whether polymorphisms in TNF-α promoter region were associated with SARS-CoV infection, development, and progression of interstitial lung fibrosis and femoral head necrosis in cure SARS patients. Considered that the progression of interstitial lung fibrosis or femoral head necrosis may be affected by hormone therapy, hormone using dosage, method and lasting period were considered in this study when analyzing the associations between gene polymorphisms with disease. abstract: BACKGROUND: Host genetic factors may play a role in the occurrence and progress of SARS-Cov infection. This study was to investigate the relationship between tumor necrosis factor (TNF)-α gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. METHODS: The association between genetic polymorphisms of TNF-α gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-α gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. PCR sequencing based typing (PCR-SBT) method was used to determine the polymorphisms of TNF-α gene in locus of the promoter region and univariate logistic analysis was conducted in analyzing the collected data. RESULTS: Compared to TT genotype, the CT genotype at the -204 locus was found associated with a protective effect on SARS with OR(95%CI) of 0.95(0.90–0.99). Also, TT genotype, CT and CC were found associated with a risk effect on femoral head necrosis with ORs(95%CI) of 5.33(1.39–20.45) and 5.67(2.74–11.71), respectively and the glucocorticoid adjusted OR of CT was 5.25(95%CI 1.18–23.46) and the combined (CT and CC) genotype OR was 6.0 (95%CI 1.60–22.55) at -1031 site of TNF-α gene. At the same time, the -863 AC genotype was manifested as another risk effect associated with femoral head necrosis with OR(95%CI) of 6.42(1.53–26.88) and the adjusted OR was 8.40(95%CI 1.76–40.02) in cured SARS patients compared to CC genotype. CONCLUSION: SNPs of TNF-α gene of promoter region may not associate with SARS-CoV infection. And these SNPs may not affect interstitial lung fibrosis in cured SARS patients. However, the -1031CT/CC and -863 AC genotypes may be risk factors of femoral head necrosis in discharged SARS patients. url: https://doi.org/10.1186/1471-2334-8-27 doi: 10.1186/1471-2334-8-27 id: cord-306983-6w2fvtfy author: Wang, Siye title: Influenza Virus—Cytokine-Protease Cycle in the Pathogenesis of Vascular Hyperpermeability in Severe Influenza date: 2010-10-01 words: 3808.0 sentences: 223.0 pages: flesch: 39.0 cache: ./cache/cord-306983-6w2fvtfy.txt txt: ./txt/cord-306983-6w2fvtfy.txt summary: Influenza A virus infection resulted in significant increases in TNF-α, IL-6, IL-1β, viral hemagglutininprocessing protease trypsin levels, and viral replication with vascular hyperpermeability in lung and brain in the first 6 days of infection. The present study reports several new observations: (1) proinflammatory cytokines, TNF-a, IL-1b, and IL-6, when upregulated by influenza A virus infection, induce trypsin expression in various organs and human endothelial cells; (2) the upregulated trypsin induces [Ca 2+ ] i mobilization via activation of the PAR-2, followed by loss of zonula occludens-1 and vascular hyperpermeability; (3) inhibitors of NF-kB and activator protein 1 effectively suppress the upregulation of proinflammatory cytokines and trypsin and improve the survival rates of infected mice. The present results allow us to propose a new mechanism of junctional permeability regulation: upregulated trypsin by influenza A virus and/or proinflammatory cytokines induces increase in [Ca 2+ ] i and loss of zonula occludens-1 in endothelial cells via PAR-2 signaling. abstract: Background. Severe influenza is characterized by cytokine storm and multiorgan failure with edema. The aim of this study was to define the impact of the cytokine storm on the pathogenesis of vascular hyperpermeability in severe influenza. Methods. Weanling mice were infected with influenza A WSN/33(H1N1) virus. The levels of proinflammatory cytokines, tumor necrosis factor (TNF) α, interleukin (IL) 6, IL-1β, and trypsin were analyzed in the lung, brain, heart, and cultured human umbilical vein endothelial cells. The effects of transcriptional inhibitors on cytokine and trypsin expressions and viral replication were determined. Results. Influenza A virus infection resulted in significant increases in TNF-α, IL-6, IL-1β, viral hemagglutininprocessing protease trypsin levels, and viral replication with vascular hyperpermeability in lung and brain in the first 6 days of infection. Trypsin upregulation was suppressed by transcriptional inhibition of cytokines in vivo and by anti-cytokine antibodies in endothelial cells. Calcium mobilization and loss of tight junction constituent, zonula occludens-1, associated with cytokine- and trypsin-induced endothelial hyperpermeability were inhibited by a protease-activated receptor-2 antagonist and a trypsin inhibitor. Conclusions. The influenza virus-cytokine-protease cycle is one of the key mechanisms of vascular hyperpermeability in severe influenza. url: https://www.ncbi.nlm.nih.gov/pubmed/20731583/ doi: 10.1086/656044 id: cord-336432-tu00gffr author: Wang, Zhiyu title: Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide date: 2020-07-07 words: 6582.0 sentences: 358.0 pages: flesch: 47.0 cache: ./cache/cord-336432-tu00gffr.txt txt: ./txt/cord-336432-tu00gffr.txt summary: In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Accordingly, we set out to identify a small molecule with the following properties: broad-spectrum anti-inflammatory mechanism of action targeting cytokines of innate immunity; low toxicity and excellent safety profile; chemically stable; easily stored and administered; able to be rapidly adopted in clinical settings worldwide; and, widespread availability with inexpensive and efficient means of production. A library of 1,136 small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. abstract: The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia (“cytokine storm”). To address this immuno-inflammatory pathogenesis, multiple clinical trials have been proposed to evaluate anti-inflammatory biologic therapies targeting specific cytokines. However, despite the obvious clinical utility of such biologics, their specific applicability to COVID-19 has multiple drawbacks, including they target only one of the multiple cytokines involved in COVID-19’s immunopathy. Therefore, we set out to identify a small molecule with broad-spectrum anti-inflammatory mechanism of action targeting multiple cytokines of innate immunity. In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. This has enabled us to identify the loop diuretic furosemide as a candidate molecule. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Upon treatment with furosemide, LPS-induced production of pro-inflammatory cytokines was reduced, indicating that furosemide suppresses the M1 polarization, including IL-6 and TNF-α release. In addition, we found that furosemide promotes the production of anti-inflammatory cytokine products (IL-1RA, arginase), indicating M2 polarization. Accordingly, we conclude that furosemide is a reasonably potent inhibitor of IL-6 and TNF-α that is also safe, inexpensive and well-studied. Our pre-clinical data suggest that it may be a candidate for repurposing as an inhaled therapy against COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32704455/ doi: 10.7717/peerj.9533 id: cord-272237-gnno6elo author: Wang, Ziran title: A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids date: 2020-07-31 words: 4472.0 sentences: 241.0 pages: flesch: 53.0 cache: ./cache/cord-272237-gnno6elo.txt txt: ./txt/cord-272237-gnno6elo.txt summary: A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). abstract: A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, a nonionic surfactant is employed to minimize the nonspecific adsorption of the biosensor, hence enabling cytokine detection (TNF-α and IFN-γ, significant inflammatory cytokines, are used as representatives) in artificial tears (used as a biofluid representative). The experimental results demonstrate that the biosensor very consistently and sensitively detects TNF-α and IFN-γ, with limits of detection down to 2.75 and 2.89 pM, respectively. The biosensor, which undergoes large deformations, can thus potentially provide a consistent and sensitive detection of cytokines in the human body. url: https://doi.org/10.3390/nano10081503 doi: 10.3390/nano10081503 id: cord-023389-ilrp8vb7 author: Wefer, J. title: Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date: 2008-06-28 words: 16845.0 sentences: 866.0 pages: flesch: 46.0 cache: ./cache/cord-023389-ilrp8vb7.txt txt: ./txt/cord-023389-ilrp8vb7.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: DNA vaccine coding for the encephalitogenic peptide MOG(91‐108) protects LEW.1AV1 from subsequent development of experimental autoimmune encephalomyelitis (EAE). Protection is associated with a type 1 immune response and is dependent on the presence of CpG DNA motifs. The mechanisms underlying the observed reduction of EAE development in protected rats have not been fully clarified. We investigated immunological characteristics of lymphocytes after DNA vaccinaton and subsequent EAE induction. We confirm that protection was not associated with suppression of T1 cells, as transcription of the novel molecule rat T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule (TIM‐3), reported to be exclusively expressed on differentiated T1 cells, was not altered by DNA vaccination. We did not note any clonal deletion upon tolerization, but detected an antigen‐specific lymphocyte population upregulating IFNγ upon recall stimulation 3 weeks after protective DNA vaccination. In protected rats, we observed (1) no alterations in antigen‐specific Th2 or Th3 responses, (2) reduced MHC II expression on splenocytes early after EAE induction, (3) antigen‐specific upregulation of IFNβ upon recall stimulation and (4) reduced IL‐12Rβ2 on lymphocytes. We thus demonstrate an association of the protective effect of DNA vaccination with expression of IFNβ. We are currently investigating the cellular mechanisms behind this IFNβ‐mediated protection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169512/ doi: 10.1111/j.0300-9475.2004.01423j.x id: cord-351387-i0zamkpd author: Witte, Katrin title: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date: 2015-09-25 words: 4360.0 sentences: 220.0 pages: flesch: 49.0 cache: ./cache/cord-351387-i0zamkpd.txt txt: ./txt/cord-351387-i0zamkpd.txt summary: In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. In the first setting, PBMCs were stimulated with EPs 7630 (3 and 30 μg/ml), Escherichia coli 0127:B8 lipopolysaccharide (TLR4 ligand; 100 ng/ml; Sigma-Aldrich), polyinosinic-polycytidylic acid [poly (I:C); 10 μg/ml; Sigma-Aldrich], a cytokine mixture of IL-1β, IL-2 and IL-12 (10 ng/ml each; R&D systems), anti-CD3 (Orthoclone; Cilag) and anti-CD28 (R&D systems) monoclonal antibodies (1 μg/ml each), or were left without specific treatment (0.1% ethanol as solvent control) for 4 and 24 h, before cell culture supernatant was recovered for ELISA cytokine production analysis. Our data show that EPs 7630 strongly and dose-dependently induced the production of the pro-inflammatory cytokines TNF-α and IL-6 in human blood immune cells. abstract: Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. url: https://www.ncbi.nlm.nih.gov/pubmed/26406906/ doi: 10.1371/journal.pone.0138075 id: cord-348391-xytmq2f2 author: Wyganowska-Swiatkowska, Marzena title: Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review date: 2020-06-30 words: 8077.0 sentences: 461.0 pages: flesch: 41.0 cache: ./cache/cord-348391-xytmq2f2.txt txt: ./txt/cord-348391-xytmq2f2.txt summary: While long term proteinase and ACE-2 inhibition could be detrimental to cellular function and bodily homeostasis, targeted treatment partially reducing the effectiveness of coronavirus S protein attachment to the ACE2 or to the priming proteinase could have the potential to drop the SARS-CoV-2 viral load before a state of septic shock is reached at the peak of infection. Aspalathin and nothofagin extracted from Rooibos have been shown to effectively inhibit LPS-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules [124] . The effect and mechanism of salidroside on sepsis-induced acute lung injury is mediated by the inhibition of inflammatory responses and HMGB1 production in bacterial LPS-treated macrophages and mice. Study has shown that pelargonidin (PEL) had effectively inhibited LPS-induced release of HMGB1 and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. abstract: By attaching to the angiotensin converting enzyme 2 (ACE2) protein on lung and intestinal cells, Sudden Acute Respiratory Syndrome (SARS-CoV-2) can cause respiratory and homeostatic difficulties leading to sepsis. The progression from acute respiratory failure to sepsis has been correlated with the release of high-mobility group box 1 protein (HMGB1). Lack of effective conventional treatment of this septic state has spiked an interest in alternative medicine. This review of herbal extracts has identified multiple candidates which can target the release of HMGB1 and potentially reduce mortality by preventing progression from respiratory distress to sepsis. Some of the identified mixtures have also been shown to interfere with viral attachment. Due to the wide variability in chemical superstructure of the components of assorted herbal extracts, common motifs have been identified. Looking at the most active compounds in each extract it becomes evident that as a group, phenolic compounds have a broad enzyme inhibiting function. They have been shown to act against the priming of SARS-CoV-2 attachment proteins by host and viral enzymes, and the release of HMGB1 by host immune cells. An argument for the value in a nonspecific inhibitory action has been drawn. Hopefully these findings can drive future drug development and clinical procedures. url: https://doi.org/10.3390/ijms21134639 doi: 10.3390/ijms21134639 id: cord-007858-1ijxilpb author: Xu, G.L. title: Attenuation of acute lung injury in mice by oxymatrine is associated with inhibition of phosphorylated p38 mitogen-activated protein kinase date: 2005-04-08 words: 4055.0 sentences: 228.0 pages: flesch: 55.0 cache: ./cache/cord-007858-1ijxilpb.txt txt: ./txt/cord-007858-1ijxilpb.txt summary: Furthermore, pretreatment with oxymatrine significantly alleviated oleic acid-induced lung injury accompanied by reduction of lung index and wet-to-dry weight ratio, decreases in serum TNF-α level and inhibition of phosphorylated p38 MAPK. These findings suggest that oxymatrine has a beneficial effect on acute lung injury induced by oleic acid in mice and may inhibit the production of proinflammatory cytokine, TNF-α, by means of the inhibition of p38 MAPK. Light microscopic findings in the lung at 6 h after oleic acid injection demonstrated a marked lung injury resembling those seen in lung of patients with ALI/ARDS, represented by prominent atelectasis, intraalveolar and interstitial patchy hemorrhage, edema, thickened alveolar septum, formation of hyaline membranes and the existence of inflammatory cells in alveolar spaces (Fig. 1A) , which were not observed in the control group (Fig. 1B) . Effect of oxymatrine on serum TNF-␣ level in mice with lung injury induced by oleic acid. abstract: Oxymatrine is one of the alkaloids extracted from Chinese herb Sophora japonica (Sophora flavescens Ait.) with activities of anti-inflammation, inhibiting immune reaction, antivirus, protecting hepatocytes and antihepatic fibrosis. However, the effect of oxymatrine on acute lung injury (ALI) has not been known yet. In this study, the effect of oxymatrine on ALI was investigated using an oleic acid-induced ALI mouse model. Morphological findings showed that the oleic acid group demonstrated a marked lung injury represented by prominent atelectasis, intraalveolar and interstitial patchy hemorrhage, edema, thickened alveolar septum, formation of hyaline membranes and the existence of inflammatory cells in alveolar spaces. While in the oxymatrine/dexamethasone group, these changes were less severe and in the vicinity of the control group. Furthermore, pretreatment with oxymatrine significantly alleviated oleic acid-induced lung injury accompanied by reduction of lung index and wet-to-dry weight ratio, decreases in serum TNF-α level and inhibition of phosphorylated p38 MAPK. These findings suggest that oxymatrine has a beneficial effect on acute lung injury induced by oleic acid in mice and may inhibit the production of proinflammatory cytokine, TNF-α, by means of the inhibition of p38 MAPK. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125571/ doi: 10.1016/j.jep.2005.01.026 id: cord-002326-3qb1ym4w author: Yang, Runkuan title: Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries date: 2016-12-03 words: 7622.0 sentences: 310.0 pages: flesch: 36.0 cache: ./cache/cord-002326-3qb1ym4w.txt txt: ./txt/cord-002326-3qb1ym4w.txt summary: EP (40 mg/kg) was intraperitoneally injected every 6 h for 48 h)] significantly ameliorates pancreatic injury and necrosis [4, 6] ; EP therapy also markedly reduces pancreatic expression of TNF-α, IL-6, HMGB1 and NF-kB DNA binding [4, 6] ; treatment with EP reduces the number of inflammatory cell infiltration and decreases the pancreatic level of lipid peroxidation, which is a parameter of ROS [4] . Hepatic I/R induces significantly increased hepatic expression of TNF-α, IL-6, HMGB1 and NF-kB activation, and hepatic I/R also induces markedly increased hepatic expression of Bcl-2, Bax, Beclin-1 and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, all of these changes are significantly reduced by EP treatment (1 h before the ischemia procedure, a single dose of EP was intraperitoneally injected to animals in the 20 mg/kg group, the 40 mg/kg group and the 80 mg/kg group, liver tissue samples were obtained 4 h, 6 h and 16 h after I/R), suggesting that EP ameliorates hepatic I/R injury via its antiinflammatory and its anti-apoptosis effect. abstract: Ethyl pyruvate (EP) is a simple derivative of pyruvic acid, which is an important endogenous metabolite that can scavenge reactive oxygen species (ROS). Treatment with EP is able to ameliorate systemic inflammation and multiple organ dysfunctions in multiple animal models, such as acute pancreatitis, alcoholic liver injury, acute respiratory distress syndrome (ARDS), acute viral myocarditis, acute kidney injury and sepsis. Recent studies have demonstrated that prolonged treatment with EP can ameliorate experimental ulcerative colitis and slow multiple tumor growth. It has become evident that EP has pharmacological anti-inflammatory effect to inhibit multiple early inflammatory cytokines and the late inflammatory cytokine HMGB1 release, and the anti-tumor activity is likely associated with its anti-inflammatory effect. EP has been tested in human volunteers and in a clinical trial of patients undergoing cardiac surgery in USA and shown to be safe at clinical relevant doses, even though EP fails to improve outcome of the heart surgery, EP is still a promising agent to treat patients with multiple inflammatory organ injuries and the other clinical trials are on the way. This review focuses on how EP is able to ameliorate multiple organ injuries and summarize recently published EP investigations. [Figure: see text] url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135784/ doi: 10.1186/s12950-016-0144-1 id: cord-307813-elom30nx author: Yip, Tsz-Fung title: Advancements in Host-Based Interventions for Influenza Treatment date: 2018-07-10 words: 15075.0 sentences: 735.0 pages: flesch: 38.0 cache: ./cache/cord-307813-elom30nx.txt txt: ./txt/cord-307813-elom30nx.txt summary: Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses. abstract: Influenza is a major acute respiratory infection that causes mortality and morbidity worldwide. Two classes of conventional antivirals, M2 ion channel blockers and neuraminidase inhibitors, are mainstays in managing influenza disease to lessen symptoms while minimizing hospitalization and death in patients with severe influenza. However, the development of viral resistance to both drug classes has become a major public health concern. Vaccines are prophylaxis mainstays but are limited in efficacy due to the difficulty in matching predicted dominant viral strains to circulating strains. As such, other potential interventions are being explored. Since viruses rely on host cellular functions to replicate, recent therapeutic developments focus on targeting host factors involved in virus replication. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. In this review, we will discuss the advancements in novel host-based interventions for treating influenza disease. url: https://doi.org/10.3389/fimmu.2018.01547 doi: 10.3389/fimmu.2018.01547 id: cord-302258-derq9b27 author: Zhang, Hui title: Effects of ubiquitin-proteasome inhibitor on the expression levels of TNF-α and TGF-β1 in mice with viral myocarditis date: 2019-08-14 words: 3444.0 sentences: 201.0 pages: flesch: 56.0 cache: ./cache/cord-302258-derq9b27.txt txt: ./txt/cord-302258-derq9b27.txt summary: Effects of ubiquitin-proteasome system (UPS) inhibitor MG-132 on the expression levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in mice with viral myocarditis were investigated to analyze the correlation of myocardial tissue score of mice between TNF-α and TGF-β1. Mortality rates of each group were recorded and compared on day 8 of modeling, and heart specimens from the remaining mice were histopathologically examined and the expression of mRNA and protein of TNF-α and TGF-β1 in myocardial tissues were detected by western blot analysis. The expression levels of myocardial histopathological scores, mRNA and protein of TNF-α and TGF-β1 in the blank and control group were significantly lower than those in the VMC and the MG-132 group. At present, few studies have reported the role of UPS in the inflammatory reaction of VMC, so we explored the effect of ubiquitin-proteasome inhibitor MG-23 on the expression levels of serum TNF-α and TGF-β1 in CVB mice, in order to understand the inflammatory mechanism of VMC. abstract: Effects of ubiquitin-proteasome system (UPS) inhibitor MG-132 on the expression levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in mice with viral myocarditis were investigated to analyze the correlation of myocardial tissue score of mice between TNF-α and TGF-β1. Eighty healthy male SPF mice aged 6 weeks were selected and 20 mice were randomly selected as the blank group. The blank group did not receive any intervention. Mortality rates of each group were recorded and compared on day 8 of modeling, and heart specimens from the remaining mice were histopathologically examined and the expression of mRNA and protein of TNF-α and TGF-β1 in myocardial tissues were detected by western blot analysis. Correlation between mouse myocardial histopathologic scores and expression of protein of TNF-α and TGF-β1 in myocardial tissues, as well as the expression of TNF-α and TGF-β1 in myocardial tissue in VMC mice was analyzed. The expression levels of myocardial histopathological scores, mRNA and protein of TNF-α and TGF-β1 in the blank and control group were significantly lower than those in the VMC and the MG-132 group. The myocardial histopathological scores, mRNA and TNF-α and TGF-β1 protein in the MG-132 group were significantly lower than those in the VMC group (P<0.05). The expression of TNF-α and TGF-β1 protein in myocardial tissues was positively correlated with the pathological score in myocardial tissue of mice (r=0.843, P<0.05; r=0.763, P<0.05), and there was a positive correlation between the expression of TNF-α and TGF-β1 protein in myocardial tissues of VMC mice (r=0.672, P<0.05). UPS inhibitor MG-132, which can significantly alleviate the myocardial injury of VMC mice, reduced the expression of inflammatory factors in myocardial tissues, and improved the survival rate of mice, thus it is a potential new treatment for VMC. url: https://www.ncbi.nlm.nih.gov/pubmed/31555373/ doi: 10.3892/etm.2019.7895 id: cord-004879-pgyzluwp author: nan title: Programmed cell death date: 1994 words: 81677.0 sentences: 4465.0 pages: flesch: 51.0 cache: ./cache/cord-004879-pgyzluwp.txt txt: ./txt/cord-004879-pgyzluwp.txt summary: Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3'' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087532/ doi: 10.1007/bf02033112 id: cord-005814-ak5pq312 author: nan title: 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date: 1995 words: 179164.0 sentences: 12028.0 pages: flesch: 56.0 cache: ./cache/cord-005814-ak5pq312.txt txt: ./txt/cord-005814-ak5pq312.txt summary: Results: In 5 patients with treated SS, 16 tests were performed (VL n=8; Dobu n=4; NA n=4 Method: Septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; MAP<70 mmHg) or the requirement for a noradrenaline (NA) infusion ~> 0.1 ~g/kg/min with a MAP _< 90mmHg. Cardiovascular support was limited to NA + dobutamine (DB), 546C88 was administered for up to 8 h at a fixed dose-rate of either i, 2.5, 5, 10 or 20 mg/kg/h iv. Methods: Fourteen cases were s~udied,their gestational age ranged from(27-32)ws.Continnous positive air way pressure was applied to six cases at Peep level from (3-6)cm H2o through nasal pronge,(group I),the other 8 cases were managed as routine,(group II).Blood gases, TcPO2,TcCo2,resp.rate,depth and pattern were monitored for assessment of tissue Oxygenation and ventilation, Results: Our rasults showed that early application of CPAP improve ventilation among (83.3%)of cases,while (16.7%)of cases need IMV.The cases of group II need IMV among (75%)of the studied cases during the second or the third day of life. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095534/ doi: 10.1007/bf02426401 id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 words: 135419.0 sentences: 7042.0 pages: flesch: 43.0 cache: ./cache/cord-006230-xta38e7j.txt txt: ./txt/cord-006230-xta38e7j.txt summary: Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100643/ doi: 10.1007/s00210-012-0736-0 id: cord-006444-eq56zhtd author: nan title: Abstracts of oral presentations and posters date: 1993 words: 40668.0 sentences: 2121.0 pages: flesch: 53.0 cache: ./cache/cord-006444-eq56zhtd.txt txt: ./txt/cord-006444-eq56zhtd.txt summary: The results from ongoing preclinical studies continue to confirm the broad spectrum of biological activities possessed by rhiL-1 1 in vitro and suggest this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation. We performed a phase H trial to assess the ability of G-CSF -mobilized PBPC to rapidly and completely restore hemopeiesis after high dose chemotherapy in the absence of bone marrow infusions, with selection for PBPC-only infusions based on yield of granulocyte -macrophage colony -forming cells (GM-CFC) after G-CSF treatment. Our approach for high-dose (HD) chemotherapy is to first treat patients eligible for dose intensification with a standard dose chemotherapy (VIP: VP26 = etoposide: 500 mg/m 2, ifosfamide: 4 g/m 2, cis-platinum: 50 mg/m 2) followed by the application of colony stimulating factors (G-CSF, GM-CSF or IL-3 + GM-CSF) in order to combine a regimen with broad anti-tumor activity with the recruitment of peripheral blood progenitor cells (PBPCs). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101830/ doi: 10.1007/bf01695978 id: cord-006828-i88on326 author: nan title: Abstracts DGRh-Kongress 2013 date: 2013-09-15 words: 30772.0 sentences: 2576.0 pages: flesch: 52.0 cache: ./cache/cord-006828-i88on326.txt txt: ./txt/cord-006828-i88on326.txt summary: Comparing gene expression profiles of yellow fever immunized individuals and active SLE patients it was possible to identify a "common" and an "autoimmune-specific" IFN signature. The inflammatory and profibrotic effects upon Aab stimulation in vitro, and their associations with clinical findings suggest a role for autoantibody-mediated activation of immune cells mediated through the AT1R and ETAR in the pathogenesis or even the onset of the disease. This study was aimed to investigate the humoral and cellular immune response to VZV including assessment of IgG-anti-VZV avidity and VZV-specific reactivity of lymphocytes in RA (n=56) or JIA patients (n=75) on different treatments, including biologic agents, such as anti-tumor-necrosis-factor(TNF)-alpha or anti-interleukin-6 (IL-6) receptor inhibition (tocilizumab), compared to 37 healthy adults (HA) and 41 children (HC). Production of cytokines by B cells in response to TLR9 stimulation inversely correlates with disease activity in SLE-patients abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103148/ doi: 10.1007/s00393-013-1255-1 id: cord-015021-pol2qm74 author: nan title: Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date: 1994 words: 162327.0 sentences: 9379.0 pages: flesch: 50.0 cache: ./cache/cord-015021-pol2qm74.txt txt: ./txt/cord-015021-pol2qm74.txt summary: It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095072/ doi: 10.1007/bf02258437 id: cord-015147-h0o0yqv8 author: nan title: Oral Communications and Posters date: 2014-09-12 words: 73711.0 sentences: 3862.0 pages: flesch: 43.0 cache: ./cache/cord-015147-h0o0yqv8.txt txt: ./txt/cord-015147-h0o0yqv8.txt summary: Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095932/ doi: 10.1007/bf03353884 id: cord-015394-uj7fe5y6 author: nan title: Scientific Abstracts date: 2008-12-23 words: 242330.0 sentences: 15267.0 pages: flesch: 52.0 cache: ./cache/cord-015394-uj7fe5y6.txt txt: ./txt/cord-015394-uj7fe5y6.txt summary: Studies involving immunohistochemical analysis of normal ovaries have shown that granulosa cells express significantly higher levels of the activator protein-1 (AP-1) transcription factor, cFos compared to theca cells, where cFos expression is virtually absent. Following acute hypoxia (0.5% O2) for one to six hours, RhoA mRNA, total protein and activation (RhoA-GTP) levels were analysed, using semi-quantitative PCRs and western blot, and compared to normoxic non-pregnant human uterine smooth muscle control cells. Since there is an urgent need for non-invasive methods for determination of fetal (F) and placental (P) function, this study was designed to evaluate the genes differently and commonly expressed in P tissue and leukocytes in maternal (M) and F circulation.Material and Methods. The current study: 1) localized IL-6 mRNA levels in preeclamptic versus normal decidual sections; 2) evaluated mechanisms regulating IL-6 synthesis by targeting intracellular signaling pathways with specific inhibitors; 3) identified potential IL-6 targets by immunolocalizing the IL-6 receptor (IL-6R) to specific cell types in placental bed biopsies. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104449/ doi: 10.1177/19337191080150020102 id: cord-016168-3hyb9stq author: nan title: Pathogenesis of Fever date: 2009 words: 4067.0 sentences: 272.0 pages: flesch: 45.0 cache: ./cache/cord-016168-3hyb9stq.txt txt: ./txt/cord-016168-3hyb9stq.txt summary: • Fever (pyrexia) is a regulated body temperature above the normal range occurring as a result of IL-1-mediated elevation of the hypothalamic set point. • Cytokines are proteins produced throughout the body, mainly by monocytes, macrophages, and T cells to regulate the immune responses within the body and control inflammatory and haematopoietic processes and may induce fever. • Pro-inflammatory cytokines (IL-1, IL-6, TNF-α, INF-γ, granulocyte-macrophage colony-stimulating factor, GM-CSF) are responsible for initiating an effective defense against exogenous organisms. Other mechanisms to initiate fever include the following: Some endotoxins, produced by bacteria, act directly on the hypothalamus to alter the set point. Mechanisms by which viruses may produce fever include direct invasion of macrophages, immunological reaction to viral components involving antibody formation, induction by INF, and necrosis of cells by viruses. Increased TNF production in Kawasaki disease may play a role in the immune activation and damage to vascular endothelial cells occurring in the disease. abstract: #x203A; Although infection is the most common cause of fever, fever is also a common finding in hypersensitivity reaction, autoimmune diseases, and malignancy. › Febrile response is mediated by endogenous pyrogens (cytokines) in response to invading exogenous pyrogens, primarily microorganisms or their direct products (toxins). › These endogenous pyrogens act on thermosensitive neurons in the hypothalamus, which ultimately upgrade the set point via prostaglandins. › The body reacts by increasing the heat production and decreasing the heat loss until the body temperature reaches this elevated set point. › Fever, in contrast to hyperthermia, will not climb up relentlessly because of an effective central control of the hypothalamic center. › Cytokines play a pivotal role in the immune response by activation of the B cells and T lymphocytes. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favor of the protective role of fever. › The protective processes of the immune response are optimal at high temperature (around 39.5°C). › Not all effects resulting from fever generation benefit the host; some are harmful and even lethal. This occurs mainly by overproduction of the cytokines or imbalance between cytokines and their inhibitors, such as severe and fulminate infections and septic shock. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120379/ doi: 10.1007/978-3-540-78598-9_3 id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 words: 188640.0 sentences: 9313.0 pages: flesch: 45.0 cache: ./cache/cord-022888-dnsdg04n.txt txt: ./txt/cord-022888-dnsdg04n.txt summary: Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. abstract: No Abtract url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/ doi: 10.1002/eji.200990224 id: cord-022940-atbjwpo5 author: nan title: Poster Sessions date: 2016-09-07 words: 241182.0 sentences: 12746.0 pages: flesch: 47.0 cache: ./cache/cord-022940-atbjwpo5.txt txt: ./txt/cord-022940-atbjwpo5.txt summary: We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164006/ doi: 10.1111/febs.13808 id: cord-023443-pvz7dll9 author: nan title: Abstracts for the Scandinavian Society for Immunology 35th Annual Meeting and 20th Summer School date: 2004-06-02 words: 16643.0 sentences: 857.0 pages: flesch: 46.0 cache: ./cache/cord-023443-pvz7dll9.txt txt: ./txt/cord-023443-pvz7dll9.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169613/ doi: 10.1111/j.1365-3083.2004.01423.x id: cord-034340-3ksfpaf7 author: nan title: Proceedings of the 26th European Paediatric Rheumatology Congress: part 2: Virtual. 23 - 26 September 2020 date: 2020-10-28 words: 35088.0 sentences: 2148.0 pages: flesch: 49.0 cache: ./cache/cord-034340-3ksfpaf7.txt txt: ./txt/cord-034340-3ksfpaf7.txt summary: Objectives: The current study was undertaken to evaluate sociodemographic and sociocultural features, parent behavior, the gestation and breastfeeding period, nutritional status of early childhood in our patients with JIA, and to determine their relationship with disease activity, damage index, remission time, and relapse rate. Methods: In the present study were included data 170 JIA(55 boys and 115 girls)aged from 2 to 17 years,who received scheduled vaccination before the age of 2 years and before JIA onset against measles,parotitis,diphtheria and rubella.Incomplete vaccination means the reduced number of vaccine to age.In all patients the Ig G anti-vaccine antibodies levels were detected with ELISA.JIA categories were:oligoarthritis -73,polyarthritis -61,systemic-16 and enthesitisrelated arthritis-20.Data presented with median and 25%>75% Results: Incomplete vaccination against MMR was in 50 (42%)diphtheria in 85 (50%) of the JIA patients. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592179/ doi: 10.1186/s12969-020-00470-5 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel Error: near line 1: database is locked Send options without primary recipient specified. 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