# ent

id: cord-001769-2sdg5ll7
type: ORG
entity:
  the Third Military Medical University Institutional Animal Care and Use Committee Supporting Information S1 Text Reagents


id: cord-014661-mrh2pbi6
type: CELL_LINE
entity:
  IGROV 1 human ovarian carcinoma cells astrocyte cells RL 7 human follicular lymphoma cells HT29 human colon carcinoma cells


id: cord-014661-mrh2pbi6
type: GGP
entity:
  Parkinson s disease Alzheimer diabetus mellitus cardiac failure atherosclerosis hypertension and anovulation 39 40 41 42 43 44 45 46 Differences between functions and regulatory mechanisms of FOXO1 and FOXO3 proteins


id: cord-014661-mrh2pbi6
type: DISEASE
entity:
  cancer neurodegenerative diseases Parkinson s disease Alzheimer diabetus mellitus cardiac failure atherosclerosis hypertension


id: cord-001347-ssrs0cwf
type: PROTEIN
entity:
  influenza virus neuraminidase 19 20 21 the virus host cell uptake 20 22 or cellular signalling events


id: cord-001347-ssrs0cwf
type: DISEASE
entity:
  influenza A H3N2 and A H1N1 viruses isolated worldwide Vaccines for pandemic influenza The history of our current vaccines their limitations and the requirements


id: cord-289034-yl3emjef
type: WORK_OF_ART
entity:
  A Case of Severe Hypermetabolism Of Nonthyroid Origin With A Defect In The Maintenance of Mitochondrial Respiratory Control A Correlated Clinical Biochemical and Morphological Study Mitochondrial diseases Contribution


id: cord-289034-yl3emjef
type: WORK_OF_ART
entity:
  The Role of Mitochondria in Inflammation From Cancer to Neurodegenerative Disorders Mitochondrial Dysfunction in Aging and Cancer Melatonin Inhibits COVID 19


id: cord-289034-yl3emjef
type: DISEASE
entity:
  hereditary paragangliomas pheochromocytomas neuroblastomas gastrointestinal tumors renal cell cancers


id: cord-013415-110b95cg
type: PROTEIN
entity:
  nuclear factor κB and AP 1 activities Hyperglycemia Induced Reactive Oxygen Species Toxicity to Endothelial Cells


id: cord-013415-110b95cg
type: WORK_OF_ART
entity:
  Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes Senescent Cells Tumor Suppression


id: cord-013415-110b95cg
type: ORG
entity:
  Chronic Diseases Chronic Inflammation Inflammaging and Its Potential Contribution to Age Associated Diseases


id: cord-102808-c7ajfvt5
type: LAW
entity:
  Measurement of Respiratory Burst Products Released or Retained During Activation of Professional Phagocytes Basic


id: cord-004508-ok3px98z
type: PROTEIN
entity:
  e vascular endothelial growth factor B VEGFB thrombospondin 2 THBS2 endothelin 1 EDN1 ET1 serine peptidase inhibitor E SERPINE1 thrombospondin 1 THBS1 chemokine ligand


id: cord-005280-a23oy0sz
type: PROTEIN
entity:
  complex III subunit Rieske and complex I subunit NDUFB4 NADH dehydrogenase ubiquinone 1 beta subcomplex subunit 4 respectively Mutants


id: cord-048478-ftlb5b95
type: DNA
entity:
  25S probe 007 position 40 lanes 1 6 probe W234 position 344 lanes 7 12 probe W236 position 600 lanes 13 18 probe W238 position 843 lanes 19 24 probe W239 position 2168 lanes 25 30


id: cord-273992-xddikzxs
type: PROTEIN
entity:
  rennin amyloglucosidases glucamylases interferons interleukins insulin monoclonal antibodies tissue plasminogen activators t PA sexually transmitted disease antigens


id: cord-034321-ohjik0pf
type: DISEASE
entity:
  ARDS acute respiratory distress syndrome CGD chronic granulomatous disease COPD chronic obstructive pulmonary disease


id: cord-012495-r6nkdeaw
type: DNA
entity:
  C G A ROSE Telethon GGP11139B to P P Progetti di Rilevante Interesse Nazionale PRIN2017E5L5P3 to P P


id: cord-012495-r6nkdeaw
type: GGP
entity:
  cytochrome c release and IP3R activity in muscular dystrophy The calcineurin signal transduction pathway is essential for successful muscle regeneration in mdx dystrophic mice


id: cord-012495-r6nkdeaw
type: ORG
entity:
  Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis


id: cord-012495-r6nkdeaw
type: WORK_OF_ART
entity:
  Potential Treatment for Acute Pancreatitis Small Molecule Inhibitors of Cyclophilins Block Opening of the Mitochondrial Permeability Transition Pore and Protect Mice From Hepatic Ischemia Reperfusion Injury Synthesis and Optimization of Diarylisoxazole 3 carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore N Phenylbenzamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore Melatonin


id: cord-035015-slgywe0c
type: WORK_OF_ART
entity:
  Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes


id: cord-035015-slgywe0c
type: WORK_OF_ART
entity:
  Redox Signaling Through Compartmentalization of Reactive Oxygen Species Implications for Health and Disease Redox


id: cord-035015-slgywe0c
type: WORK_OF_ART
entity:
  In Mice Regulation of MAVS Expression and Signaling Function in the Antiviral Innate Immune Response Mitochondria


id: cord-035015-slgywe0c
type: WORK_OF_ART
entity:
  Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival


id: cord-003841-7uaj9hmx
type: ORG
entity:
  CXCL 8 Secretion Induction of Apoptosis and Promotion of Efferocytosis Anti Inflammatory Benefits of


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  IgE Antikörper auf Mastzellen und Basophilen Granulozyten Anaphylatoxine eine Reihe von Cytokinen Bradikinin Substanz P und darüber hinaus unspezifi sche physikalisch chemische Reize wie thermische chemische und mechanische Einwirkungen Histaminwirkungen Die Wirkung


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  einer Zufuhr von Histamin mit der Nahrung Analog zur Biosynthese im Organismus kann Histamin auch durch bakterielle Decarboxylierung aus Histidin entstehen Mögliche Quellen von Histamin sind bakteriell verdorbene histidinreiche Nahrungsmittel wie etwa mangelhaft gekühlter Fisch Besonders histidinreich sind Makrelenartige wie Sardinen


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  C5 Atom entsteht 5 Hydroxy Tryptophan aus dem b nach einer Decarboxylierung 5 Hydroxy Tryptamin 5HT Serotonin wird Der


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  ist S 222 Gelangt Serotonin massiv ins Blut ergibt sich für die Gesamtzirkulation ein Blutdruckabfall


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  Tc Zellen zur Cytotoxizität angeregt bei der sie Perforine als cytotoxische Waffe einsetzen S 236 Die ADCC ist bei der Tumorabwehr Transplantatabstoßung Infektabwehr und bei Autoimmunerkrankungen von großer


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  Eotaxin trägt wesentlich zur Massenansammlung von Eosinophilen Granulozyten an Orten anaphylaktischer Reaktionen bei Konzentrationsabhängig werden darüber hinaus Adhäsion Granulaabgabe und ROS Produktion angeregt Eotaxin


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  nach drei Tagen deutlich erhöht und erreicht bei komplikationsfreiem Verlauf zwischen dem siebenten bis 12 Tag ein


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  Der Schwanzteil kann auch Strukturen wie Makromoleküle oder Vesikel binden und entlang Aktin intrazellulär transportieren b Verbinden sich zwei Myosin


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  mit einem Schlag freisetzt Allgemeines Phylogenetisch hat sich Phagozytose allem Anschein nach aus dem Fressakt von


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  Phagozyten sind der C3b Rezeptor CR1 CD 35 CD11b CD18 und CD11c CD18 S 95 Tabelle 4 Spezifi sches Immunsystem Der Fc Teil von IgG


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  Der Gehalt ist bei Infekten erhöht bei manchen Leukämien und auch bei Diabetes mellitus dagegen verringert Manche erbliche Glykogendefekte


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  nicht merklichem Ausmaß und werden nach Alterung aus dem Verkehr gezogen Anders bei Defekten der Strombahn An Orten mit starken


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  eine Ketonkörperbelastung frühzeitig zur Ketoazidose Die Säurebelastung kann bei Gichtkranken zum Anfall führen Bei Alkoholikern kann Fieber ein Delir


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  Schmerz mit dem Bewusstsein und folglich zusammen mit der Ausbildung des Telencephalons Wird das Bewusstsein ausgeschaltet fehlt auch


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  Abb 104 Hemmung der Entzündungsaktivität durch Glucocorticoide auf zellulärer Ebene 1 Synthetische wie natürliche Glucocorticoide Cortisol diffundieren durch


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  Vermehrung Differenzierung Reifung von Zellen der myeloischen Reihe und letztendlich der Freisetzung reifer Differenzierungsprodukte aus dem Knochenmarksspeicher


id: cord-020646-s7eopu9y
type: PROTEIN
entity:
  NOSTAR auch NSAR verwendet Die cP deckt aber bei weitem nicht das Einsatzgebiet dieser Entzündungshemmer


id: cord-020646-s7eopu9y
type: CL
entity:
  Schwann schen Zellen Monozyten B Lymphozyten und Mastzellen Funktionen NGF steuert das Wachstum und die Differenzierung von Nervenzellen Es ist für auswachsende Neurone


id: cord-020646-s7eopu9y
type: GGP
entity:
  Wirkung somit ausgeschaltet wird Die Gefahr dieses Regelmechanismus besteht allerdings darin dass sich bei massiver systemischer Wirkstofffreisetzung die APP Vorräte im


id: cord-020646-s7eopu9y
type: GGP
entity:
  Primärkontakt mit dem Antigen fünf bis 10 Tage bei Wiederkontakt Sekundärkontakt etwa zwei bis drei Tage wobei die Art und Applikation des Antigens und die individuelle Disposition auf die Immunantwort starken Einfl uss nehmen Bereits vorhandene AK reagieren mit AG sofort und bieten


id: cord-020646-s7eopu9y
type: GGP
entity:
  Salicylsäurederivate z B Acetylsalicylsäure Anthranilsäurederivate z B Etofenamat Essigsäurederivate z B Indomethacin und Propionsäurederivate z B Iboprufen Hemmer S 37 sind dagegen Abkömmlinge von Sulfonamiden und verwandten Schwefelverbindungen lichen Metapher die Entzündung als kriegerischen Akt dar mit dem sich ein Organismus gegen einen Feind


id: cord-020646-s7eopu9y
type: DISEASE
entity:
  Plasmabestandteile wird durch Lückenbildung im Endothelbelag der Venolen erhöht Permeabilitätssteigerung


id: cord-020646-s7eopu9y
type: CHEMICAL
entity:
  Medikamente sind beim Anaphylaktischen Schock zur Kreislaufstabilisierung wirksam Moderne Therapieschemata


id: cord-020646-s7eopu9y
type: CHEMICAL
entity:
  sind bakteriell verdorbene histidinreiche Nahrungsmittel wie etwa mangelhaft gekühlter Fisch Besonders histidinreich sind Makrelenartige wie


id: cord-020646-s7eopu9y
type: CHEMICAL
entity:
  Thrombopenie bis zur völligen Knochenmarkszerstörung aplastisches Syndrom Panmyelophthise führen Erhöhung


id: cord-020646-s7eopu9y
type: CHEMICAL
entity:
  cytotoxische Waffe einsetzen S 236 Die ADCC ist bei der Tumorabwehr Transplantatabstoßung Infektabwehr


id: cord-020646-s7eopu9y
type: DISEASE
entity:
  inaktiven Vorläuferproteinen durch Proteolyse entsteht Die Vorläufer werden von aktivierten Thrombozyten


id: cord-020646-s7eopu9y
type: CHEMICAL
entity:
  Chemoattraktants gesteuert wird Der Wirkungsgrad dieser Chemoattraktants ist allerdings je nach Gewebszugehörigkeit


id: cord-020646-s7eopu9y
type: CHEMICAL
entity:
  zu machen Eine Temperaturerhöhung bis zum kritischen Wert von 40 C bedeutet grundsätzlich eine Erhöhung


id: cord-020646-s7eopu9y
type: CHEMICAL
entity:
  S 274 antworten häufi g auf Entzündungen mit nur geringem Temperaturanstieg dekompensieren jedoch rasch in Richtung eines Coma


id: cord-020646-s7eopu9y
type: DISEASE
entity:
  weiter begünstigt Glucocorticoide sollen daher nur nach strenger Indikationsstellung und wenn nicht umgehbar unter


id: cord-020646-s7eopu9y
type: CHEMICAL
entity:
  diesen Schmerzvermittlern zu sagen dass sie allein kaum oder nur geringgradig Schmerz auslösen aber durch weitere


id: cord-017817-ztp7w9yh
type: PROTEIN
entity:
  AMPactivated protein kinase S phase kinase associated protein 2 p45 coactivatorassociated arginine methyltransferase 1


id: cord-017817-ztp7w9yh
type: PROTEIN
entity:
  CNC homology ECH associated protein 1 Nrf2 nuclear factor erythroid 2 p45 related factors 2 sMAF small musculoaponeurotic fibrosarcoma Ub Ub Ub poly ubiquitin chain


id: cord-017817-ztp7w9yh
type: PROTEIN
entity:
  transcription factor CHOP cytidine cytidine adenosine adenosine thymidine enhancer binding homologous protein eIF2α eukaryotic translational initiation factor 2α ER


id: cord-017817-ztp7w9yh
type: GGP
entity:
  protein kinase S phase kinase associated protein 2 p45 coactivatorassociated arginine methyltransferase 1 regulatory axis


id: cord-293319-oo0w6faj
type: PROTEIN
entity:
  Ag 3 PO 4 date 2020 06 11 journal J Anal Sci Technol DOI 10 1186 s40543 020 00220 y sha afa1c0bc965c3e39a251b1393eaf2e1f9089afb7 doc_id 293319


id: cord-257514-gw9xnb4x
type: PROTEIN
entity:
  specificity phosphatase 1 DUSP1 HSP70 protein Nrf 2 HO 1 TNF NF B INF Fas FasL IL 1 IL 1 IL 6 IL 8 IL


id: cord-257514-gw9xnb4x
type: CELL_TYPE
entity:
  CD8 T cells 123 8 Oxidative Medicine and Cellular Longevity Wang et al interestingly discovered that cytotoxinassociated gene A cytotoxin a virulence factor


id: cord-278846-nqj7ctk3
type: PROTEIN
entity:
  Mer tyrosine kinase MerTK sialic acid dependent adhesion molecule SiglecF hormone receptor F4 8 glycoprotein CD64


id: cord-278846-nqj7ctk3
type: GGP
entity:
  transforming growth factor beta receptor TGF βR interleukin IL 10 receptor IL 10R CD200 receptor CD200R


id: cord-278846-nqj7ctk3
type: CL
entity:
  proinflammatory host responses 2 For example severe Coronavirus disease 19 COVID 19 associated pneumonia patients may exhibit features of systemic hyper inflammation also known as macrophage activation syndrome or cytokine storm which is associated with sustained elevation of macrophage monocytederived pro inflammatory cytokines e g IL 6 IL 8 TNF α IL 1β


id: cord-278846-nqj7ctk3
type: DISEASE
entity:
  asthma chronic obstructive pulmonary disease COPD cystic fibrosis CF idiopathic pulmonary fibrosis IPF


id: cord-273093-u79r80ip
type: GGP
entity:
  Rev Immunol DOI 10 1038 s41577 020 0407 1 sha 7736bde6a21b674ca6b779df0fcfaa379b12d2ec doc_id 273093 cord_uid u79r80ip The


id: cord-313825-bbjxd86y
type: GGP
entity:
  processes 3 4 7 14 24 Anthropogenic sources of outdoor PM are hightemperature processes e g welding smelting combustion e g power generation land traffic residential


id: cord-271939-m1ko4yal
type: DNA
entity:
  3390 antiox9080727 sha b0f42c890cd7093ff951c80e111fab99620d165b doc_id 271939 cord_uid m1ko4yal Manganosalen complexes


id: cord-288238-36hiiw91
type: GGP
entity:
  peroxisome proliferator activated receptors α and γ Differential activation of peroxisome proliferator activated receptors


id: cord-291559-h6czy5bh
type: CL
entity:
  Ecklonia biruncinata Ecklonia brevipes Ecklonia cava EC Ecklonia fastigiata Ecklonia kurome EK Ecklonia maxima EM Ecklonia muratii Ecklonia radiate ER and Ecklonia stolonifera ES Hornemann 1828 Moon et al 2008 EC an edible marine brown alga


id: cord-291559-h6czy5bh
type: GGP
entity:
  gp91 phox a catalytic component of the nicotinamide adenine dinucleotide phosphate NADPH oxidase complex


id: cord-260348-83ftjqev
type: GGP
entity:
  Curcumin 0 02 mg mL 0 001 mg mL and 0 005 mg mL treated groups were significantly lowered in a dose dependent manner The results of Annexin V FITC PI JC 1


id: cord-331673-xv1tcugl
type: ORG
entity:
  Novel Emerging Antiviral Therapeutic Agents High Efficiency of Functional Carbon Nanodots as Entry Inhibitors


id: cord-331673-xv1tcugl
type: ORG
entity:
  Feline Calicivirus Novel Antiviral Characteristics of Nanosized Copper i Iodide Particles Showing Inactivation Activity


id: cord-331673-xv1tcugl
type: WORK_OF_ART
entity:
  Replication by Affecting Virus Maturation without Impairing Protease Activity A New Family of Fullerene Derivatives


id: cord-331673-xv1tcugl
type: WORK_OF_ART
entity:
  Versatile Nanoplatform for Entrapment of Guanine Based Drugs Intracellular Trafficking and Therapeutic Outcome of Multiwalled Carbon Nanotubes


id: cord-331673-xv1tcugl
type: WORK_OF_ART
entity:
  Nanoparticles Promoting Both Humoral and Cellular Immune Responses to HCV Recombinant Proteins DNA Vaccines


id: cord-331673-xv1tcugl
type: ORG
entity:
  Immunization Nanodiamond Enhances Immune Responses in Mice against Recombinant HA H7N9 Assessment of Gold Nanoparticles


id: cord-331673-xv1tcugl
type: ORG
entity:
  a Size Dependent Vaccine Carrier for Enhancing the Antibody Response against Synthetic Foot And Mouth Disease Virus Peptide Consensus M2e Peptide Conjugated to Gold Nanoparticles Confers Protection


id: cord-331673-xv1tcugl
type: DISEASE
entity:
  Herpes Simplex Virus Type 1 Interaction of Silver Nanoparticles with HIV 1 Silver Nanoparticles Impair Peste Des Petits


id: cord-316244-s5ua0re3
type: ORG
entity:
  Proteomic Identification of Overexpressed PRDX 1 and Its Clinical Implications in Ovarian Carcinoma Neuroprotective


id: cord-316244-s5ua0re3
type: ORG
entity:
  Protection of Respiratory Syncytial Virus Induced Cysteinyl Oxidation of Nuclear Cytoskeletal Proteins Phosphorylation


id: cord-316244-s5ua0re3
type: WORK_OF_ART
entity:
  a More Active and Robust Peroxidase Multiple Functions of Peroxiredoxins Peroxidases Sensors and Regulators of the Intracellular Messenger H 2 O 2 and Protein Chaperones Peroxiredoxins A


id: cord-316244-s5ua0re3
type: WORK_OF_ART
entity:
  Proteins in Endothelial Cells Peroxiredoxin 1 Promotes Pancreatic Cancer Cell Invasion by Modulating


id: cord-316244-s5ua0re3
type: DISEASE
entity:
  squamous cell carcinoma bladder cancer lung cancer prostate cancer hepatocellular carcinoma esophageal squamous cell carcinoma


id: cord-335676-7ak53hto
type: PROTEIN
entity:
  angiotensin converting enzyme ACE angiotensin II Ang II angiotensin receptor type 1 AT1 ACE Ang II AT1


id: cord-336201-fl606l3b
type: PROTEIN
entity:
  mannose binding lectin MBL surfactant protein D SP D dendritic cell specific intercellular adhesion molecule 3


id: cord-336201-fl606l3b
type: PROTEIN
entity:
  granulocyte colony stimulating factor G CSF macrophage inflammatory protein 1α MIP1α serum ferritin fibrinogen plasminogen C reactive protein CRP


id: cord-336201-fl606l3b
type: GGP
entity:
  antibioticresistant Escherichia coli Proteus spp Klebsiella spp coagulasenegative staphylococci Enterobacter


id: cord-310723-ogo9mvi5
type: GGP
entity:
  Antioxidants 2020 9 x FOR PEER REVIEW 14 of 29 As we have mentioned above in 122 a change in the signal in this region after BSA


id: cord-297469-26d8o1xk
type: PROTEIN
entity:
  granulocyte macrophage colony stimulating factor GM CSF transforming growth factor beta 1 TGF β1 and tumor necrosis factor alpha TNF


id: cord-313918-uv9xdp5f
type: GGP
entity:
  glyoxalase II GLO2 Glutathione GSH glutathione disulfide GSSG glutathione reductase GR glutathione S transferase GST GSH ethyl ester


id: cord-313918-uv9xdp5f
type: GGP
entity:
  sterol regulatory element binding protein 2 SREBP 2 thioredoxin 2 thioredoxin reductase 2 Trx2 TrxR2 tumor necrosis factor TNF Intracellular cysteine


id: cord-313918-uv9xdp5f
type: WORK_OF_ART
entity:
  Hepatocytes A Diagnostic Hint for Alcoholic Liver Disease PubMed Effects of Ethanol on Proteins of Mitochondrial Membranes


id: cord-268122-74nj66vb
type: PROTEIN
entity:
  nicotinamide nucleotide transhydrogenase G3PDH glyceraldehyde 3 phosphate dehydrogenase 6PGD 6phosphogluconate dehydrogenase G6PD glucose 6 phosphate dehydrogenase GPx glutathione peroxidases IDH1 2 isocitrate dehydrogenase 1 and 2 MDH malate dehydrogenase ME1 3 malic enzyme NADK NAD kinase NOXs NADPH oxidases OXPHOS


id: cord-268122-74nj66vb
type: PROTEIN
entity:
  peroxiredoxin GPx glutathione peroxidases SOD1 2 superoxide dismutase 1 and 2 Trx thioredoxin TrxR thioredoxin reductases XO xanthine oxidase


id: cord-268122-74nj66vb
type: PROTEIN
entity:
  nitric oxide synthase ISGs interferon stimulated genes IV Influenza virus KSHV Kaposi s sarcoma associated herpesvirus MPO myeloperoxidase Mtb Mycobacterium tuberculosis NOXs NADPH oxidases


id: cord-268122-74nj66vb
type: GGP
entity:
  nicotinate mononucleotide QPRT quinolinate phosphoribosyl transferase NAPRT nicotinic acid phosphoribosyltransferase


id: cord-268122-74nj66vb
type: GGP
entity:
  NAD kinases PARPs poly ADP ribose polymerases NNT nicotinamide nucleotide transhydrogenase TDO tryptophan 2 3 dioxygenase SARM1


id: cord-268122-74nj66vb
type: GGP
entity:
  NNMT Nicotinamide N methyltransferase NMN nicotinamide mononucleotide PUFAs polyunsaturated fatty acids


id: cord-268122-74nj66vb
type: GGP
entity:
  glutamate dehydrogenase NNT nicotinamide nucleotide transhydrogenase G3PDH glyceraldehyde 3 phosphate dehydrogenase 6PGD 6phosphogluconate dehydrogenase G6PD glucose 6 phosphate dehydrogenase GPx glutathione peroxidases IDH1 2 isocitrate dehydrogenase 1


id: cord-268122-74nj66vb
type: CL
entity:
  LOX NAD nicotinamide adenine dinucleotide NOXs NADPH oxidases NADPH nicotinamide adenine dinucleotide phosphate


id: cord-268122-74nj66vb
type: GGP
entity:
  Alzheimer s disease and amyotrophic lateral sclerosis Could sirtuin activities modify ALS onset and progression Pathways to mitochondrial


id: cord-268122-74nj66vb
type: DISEASE
entity:
  papillary thyroid cancer renal clear cell carcinoma glioblastoma tumors bladder cancer colorectal cancers gastric cancers


id: cord-307148-k1uo3fxm
type: CELL_LINE
entity:
  AEC II alveolar epithelial cell types I and II DCs dendritic cells FOXO1 forkhead box O1 transcription factor FOXO3 forkhead box O3


id: cord-307148-k1uo3fxm
type: PROTEIN
entity:
  Glut3 glucose transporters 1 and 3 MCT monocarboxylate transporter NNT nicotinamide nucleotide transhydrogenase PDC pyruvate dehydrogenase complex 5


id: cord-307148-k1uo3fxm
type: PROTEIN
entity:
  nuclear respiratory factor 1 NRF1 Abbreviations Ac acetate ARE antioxidant response element CA9 carbonic anhydrase 9 CCR7 C C chemokine receptor type 7 ERR


id: cord-307148-k1uo3fxm
type: PROTEIN
entity:
  heme oxygenase 1 SOD2 263 NADP H quinone oxidoreductase NQO1 gamma glutamylcysteine synthetase GCLC thioredoxin TXN thioredoxin reductase 1 TXNRD1 264


id: cord-307148-k1uo3fxm
type: PROTEIN
entity:
  antioxidant transcriptional master regulator Nrf2 Nitric oxide donor S nitroso N acetylpenicillamine


id: cord-307148-k1uo3fxm
type: GGP
entity:
  box O3 transcription factor HIF 1α hypoxia inducible factor 1 alpha IFN interferon IL 6 interleukin 6 IRF3 IFN regulatory factor 3


id: cord-307148-k1uo3fxm
type: GGP
entity:
  carbonic anhydrase 9 CCR7 C C chemokine receptor type 7 ERR α estrogen related receptor alpha ETC electron transport chain K lysine


id: cord-307148-k1uo3fxm
type: GGP
entity:
  PPARG coactivator 1 alpha PHD2 prolyl hydroxylase domain protein 2 pVHL von Hippel Landau tumor suppressor protein SCOT OXCT1 succinyl CoA 3 oxaloacid CoA transferase


id: cord-307148-k1uo3fxm
type: GGP
entity:
  NADP H quinone oxidoreductase NQO1 gamma glutamylcysteine synthetase GCLC thioredoxin TXN thioredoxin reductase 1 TXNRD1


id: cord-032561-x3qbqy69
type: DNA
entity:
  reference 45 40 Orthoester Imine 34 Hydrazone 35 36 Ester 37 Acetal 38 39 Cis aconityl 40 Orthoester 41 42 Silyl ether 43 c


id: cord-032561-x3qbqy69
type: ORG
entity:
  Responsive Nanoparticles for Drug Delivery Integrated Nanoparticles to Synergistically Elevate Tumor Oxidative Stress and Suppress Antioxidative Capability for Amplified Oxidation Therapy


id: cord-032561-x3qbqy69
type: ORG
entity:
  Sensitive Dissociable Nanoscale Coordination Polymers with Drug Loading for Synergistically Enhanced Chemoradiotherapy Synthesis


id: cord-032561-x3qbqy69
type: ORG
entity:
  Two Stage Rocket Mimetic Drug Delivery System for Improved Tumor Accumulation and Safe Chemotherapy Bond Energy Data Summarized


id: cord-032561-x3qbqy69
type: ORG
entity:
  The Smart Drug Delivery System and Its Clinical Potential Proline Isomerization Regulated Tumor Microenvironment Adaptable Self Assembly of Peptides for Enhanced Therapeutic Efficacy


id: cord-032561-x3qbqy69
type: WORK_OF_ART
entity:
  the Treatment of Rheumatoid Arthritis Phospholipase A2 Enzymes Physical Structure Biological Function Disease Implication Chemical Inhibition and Therapeutic Intervention Expression of Group IIa Secretory Phospholipase A2 Increases with Prostate Tumor Grade Overexpression of group


id: cord-032561-x3qbqy69
type: WORK_OF_ART
entity:
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  Vivo Light Controlled Tools A DNA Azobenzene Nanopump Fueled by Upconversion Luminescence for Controllable Intracellular Drug Release Photo pH


id: cord-032561-x3qbqy69
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  Photoswitchable Organocatalysis Using Light to Modulate the Catalytic Activities of N Heterocyclic Carbenes


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  Fluorescent Probes for Monitoring Intracellular Enzymatic Transformations Engineered pH Responsive Mesoporous Carbon Nanoparticles for Drug Delivery Reactive Oxygen Species ROS Responsive Polymersomes with Site Specific Chemotherapeutic Delivery into Tumors via Spacer Design Chemistry Rational Design of Latent Fluorophores


id: cord-032561-x3qbqy69
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  Functional Molecular Systems From Self Immolative Dendrimers to Long Wavelength Fluorescent Dyes Development


id: cord-032561-x3qbqy69
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  the Treatment of Rheumatoid Arthritis Stabilizing p Dithiobenzyl Urethane Linkers without Rate Limiting Self Immolation for Traceless Drug Release Design and Synthesis of New Protease


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  Role of Immunity and Inflammation in the Pathophysiology of Neurodegenerative Diseases Dysregulation of Mitochondrial Calcium Signaling


id: cord-032561-x3qbqy69
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  poly ester carbamate triblock copolymers PAUR S S 62 63 Vinyldithioether Int J Mol Sci 2020 21 x FOR PEER


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  purine nucleotides cyclic adenosine 3 5 monophosphate cAMP and cyclic guanosine 3 5 monophosphate cGMP


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  cGMP dependent kinase I substrate complexes Salb K Schlossmann J Universität Regensburg Lehrstuhl Pharmakologie Universitätsstrasse 31 93053 Regensburg


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  phospholipase Cmediated signalling Walliser C Löschmann Y Ziegler V Kühne E Schilling P Rasonabe Z Bühler A Vatter P Gierschik P Universitätsklinikum Ulm Institut für Pharmakologie und Toxikologie Albert Einstein Allee 11 89081 Ulm Germany Rho GTPases


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  cGMP s potential pro and or anti tumor activities are not well understood This study has examined the expression and function of components of the cGMP pathway


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  ABCC2 c 24C T rs717620 SLCO19A1 c 80G A p His27Arg rs1051266 SLCO1B1 c 521T C p Val174Ala rs4149056 and SLCO1B1 388A G p Asn130Asp


id: cord-006230-xta38e7j
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  cGMP dependent kinase I substrate complexes Salb K Schlossmann J Universität Regensburg Lehrstuhl Pharmakologie Universitätsstrasse 31 93053 Regensburg Germany The cGMP dependent kinases cGKs


id: cord-006230-xta38e7j
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  n 4 7 P 0 05 Despite significantly higher vascular levels of nitrotyrosine and peroxynitrite neointima


id: cord-006230-xta38e7j
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id: cord-006230-xta38e7j
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entity:
  Fleck S C Pfeiffer E Metzler M KIT Institute of Applied Biosciences Chair of Food Chemistry Adenauerring


id: cord-006230-xta38e7j
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  Huppmann R Governmental Institute of Public Health of Lower Saxony Division of Environmental Medicine and


id: cord-006230-xta38e7j
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  Correlation of Structural Class with No Observed Effect Levels A Proposal for Establishing a Threshold of Concern


id: cord-006230-xta38e7j
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  CXCR7 C terminal domain influences the ligand uptake degradation rate G protein coupling and stability of the receptor This


id: cord-006230-xta38e7j
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id: cord-022940-atbjwpo5
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entity:
  P Boltovets 1 R Radutny 2 T Shevchenko 3 1 Institute of Semiconductor Physics NAS of Ukraine Kyiv Ukraine 2 Scientific and Technical Center of Advanced Technologies NAS of Ukraine Kyiv Ukraine 3 Taras Shevchenko National Univercity


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id: cord-022940-atbjwpo5
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  translation C B arria S Domingues C Arraiano Instituto de Tecnologia Qu ımica e Biol ogica Lisbon Portugal Ribonucleases RNases


id: cord-022940-atbjwpo5
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entity:
  fibrin fragment DD T Yatsenko V Rybachuk L Kapustianenko S Kharchenko O Yusova T Grinenko Palladin Institute of Biochemistry


id: cord-022940-atbjwpo5
type: PROTEIN
entity:
  Carbohydrate antigen 19 9 cancer antigen 125 cancer antigen 15 3 prostate specific antigen alphafetoprotein


id: cord-022940-atbjwpo5
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id: cord-022940-atbjwpo5
type: DNA
entity:
  anti eIF2C miR 17 5p miR 23a miR 23b miR 542 3p miR 21 miR 199a miR 705 miR 20a miR 26a miR 125b miR 200a b c


id: cord-022940-atbjwpo5
type: PROTEIN
entity:
  protein cavity S Ciambellotti 1 C Bernacchioni 2 F Scaletti 3 P Turano 1 1 CERM Magnetic Resonance Centre Florence Italy 2 Department of Biochemical Sciences University of Florence Florence Italy 3 Chemistry Department Ugo Schiff Florence Italy Ferritin


id: cord-022940-atbjwpo5
type: CELL_TYPE
entity:
  human mesenchymal stem cells S K ose 1 F Aerts Kaya 1 D Uc ßkan C ß etinkaya 1 P Korkusuz 2 1 Stem Cell Research


id: cord-022940-atbjwpo5
type: DNA
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  birches E Shadenova 1 2 E Zhumabekov 2 M Sembekov 2 M Burchaeva 2 1 Institute of General Genetic and Cytology Almaty 2


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id: cord-022940-atbjwpo5
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  S aureus S epidermidis E coli P aeruginosa P vulgaris K pneumoniae C albicans C glabrata C guilliermondii C tropicalis C parapsilosis


id: cord-022940-atbjwpo5
type: PROTEIN
entity:
  olive splicing factor 3B subunit 1 M Nurcin E Dundar Department of Molecular Biology and Genetics Balikesir University Balikesir Turkey Splicing factor 3B subunit 1 SF3B1


id: cord-022940-atbjwpo5
type: PROTEIN
entity:
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id: cord-022940-atbjwpo5
type: PROTEIN
entity:
  erythrocyte antioxidant enzymes copper zinc superoxide dismutase CuZn SOD catalase CAT glutathione peroxidase GPx1


id: cord-022940-atbjwpo5
type: PROTEIN
entity:
  superoxide dismutase SOD catalase CAT glutathione S transferase GST glutathione reductase GR glutathione peroxidase


id: cord-022940-atbjwpo5
type: PROTEIN
entity:
  superoxide dismutase SOD catalase CAT glutathione peroxidase GPx glucose 6 phosphate dehydrogenase G6PD


id: cord-022940-atbjwpo5
type: GGP
entity:
  tyrosine p 0 002 isoleucine p 0 001 leucine p 0 001 lysine p 0 008 methionine p 0 008 cysteine p 0 008 tryptophan p 0 000 and glutamic acid p


id: cord-022940-atbjwpo5
type: GGP
entity:
  Mussayeva 1 2 B Bekmanov 1 2 A Amirgalieva 2 K Dosybaev 1 2 Z Orazymbetova 1 2 R Zhapbasov 2 A Zhomartov 2 N Zumadillaev 3 N Zumadillaev 3 1


id: cord-022940-atbjwpo5
type: CL
entity:
  RBC MCV and RDW are different from the RIs suggested by the manufacturer We believe that using this relatively easy technique every laboratory can produce its own iRIs divided where possible according to sex and age and according to local conditions These ranges can be complementary to dRIs obtained for reference individuals


id: cord-022940-atbjwpo5
type: GGP
entity:
  Photosystem I P 02 08 5 005 Nigella sativa reduces paracetamol induced nephrotoxicity and oxidative stress in rats


id: cord-022940-atbjwpo5
type: GGP
entity:
  superoxide dismutase SOD catalase CAT glutathione S transferase GST glutathione reductase GR glutathione peroxidase GSH


id: cord-022940-atbjwpo5
type: GGP
entity:
  berberine F Aygenli H C ß imen Yeditepe Proteomics and Mass Spectrometry Group YediPROT Genetics and Bioengineering Yeditepe


id: cord-022940-atbjwpo5
type: ORG
entity:
  Yıldız Technical University Scientific Research Projects Coordination Department Project Number 2014


id: cord-022940-atbjwpo5
type: ORG
entity:
  the University of Bucharest ICUB Bucharest Romania 3 Faculty of Biology University of Bucharest Bucharest Romania Patients


id: cord-022940-atbjwpo5
type: FAC
entity:
  D Velic S Henry C Charlier M Popova P Weigel J Masson I Nabiev F Fleury CNRS University of Nantes Nantes France


id: cord-022940-atbjwpo5
type: FAC
entity:
  A Ugur Kurtoglu 1 V Aslan 2 E Kurtoglu 2 1 Department of Biochemistry Antalya Education and Research Hospital Antalya


id: cord-022940-atbjwpo5
type: PERCENT
entity:
  3 1 Shubnikov Institute of Crystallography of FSRC Crystallography and Photonics RAS Moscow Russia 2


id: cord-022940-atbjwpo5
type: PRODUCT
entity:
  J K Hyun 1 2 3 J Kim 1 2 J Y Hong 1 1 Dankook University Cheonan South Korea 2 Institute of Tissue Regeneration Engineering


id: cord-022940-atbjwpo5
type: ORG
entity:
  CDE European University Association Council on Doctoral Education FEBS Education Committee Federation of European Biochemical Societies


id: cord-022940-atbjwpo5
type: ORG
entity:
  University of Balikesir Faculty of Veterinary Balikesir 2 University of Balikesir Faculty of Arts and


id: cord-022940-atbjwpo5
type: ORG
entity:
  Department of Medical Genetic Turgut Ozal University Ankara 2 Faculty of Medicine Turgut Ozal University


id: cord-022940-atbjwpo5
type: ORG
entity:
  the Cerrahpasa Medical Faculty Hospital Department of Neurology and Department of Internal Medicine Geriatrics


id: cord-022940-atbjwpo5
type: PERCENT
entity:
  3 1 Gaziantep University School of Medicine Gaziantep 2 Haran University Sanliurfa 3 Department of Neurosurgery Medical School Gaziantep


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  used 4nitrophenyl butyrate 4 nitrophenyl caprylate 4 nitrophenyl laurate 4 nitrophenyl myristate 4 nitrophenyl palmitate


id: cord-022940-atbjwpo5
type: DISEASE
entity:
  drug adverse reactions I Lupu 1 I Gheorghe 2 3 M Popa 2 3 A Ion 3 M Mihai 1 V Lazar 2 3 M C Chifiriuc 2 3 1 Carol Davila


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  myristicin 3 4 5 trimethoxyphenyl 4 methoxyphenyl dillapiol 3 methoxyphenyl 3 4dimethoxyphenyl 2 3 4 5 tetramethoxyphenyl derivatives A methylenedioxy moiety


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  cefuroximesodium ampicillin sulbactam amoxicillin trihydrate potassium clavulanate cefazolin sodium gentamicin sulfate


id: cord-022940-atbjwpo5
type: DISEASE
entity:
  crimean Congo hemorrhagic fever I B ut un 1 S Sahin 1 F Duygu 2 1 University of Gaziosmanpasa Department of Biochemistry Tokat Turkey 2


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  extract precursor microRNA sequences 111 of precursor sequences showing 100 homology to Triticum urartu genome were


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  K Demirsoy 1 N Eruygur 2 E S uleymanoglu 3 1 Biotechnology Central Laboratory Biotechnology Institute Ankara University Ankara Turkey 2 Department of Pharmacognosy Faculty of


id: cord-022940-atbjwpo5
type: DISEASE
entity:
  banana mushroom butter lettuce Napoleon grape potato coffee marula fruit artichoke heads longan fruit tobacco wheat flour


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  NH 4 2 SO 4 the enzyme activity recovery and purification fold of interfacial phase for t butanol ratio 1 0 5 1 1 1 1 5 1 2 were 61 6 48 1 127 6 126 1 and 1 79 0 6 1 84 1 41 Finally


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  Butanoic acid hexadecanoic acid palmitic acid 7 Methyl Z tetradecen 1 ol acetate octadecanoic acid stearic acid


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  K Dobrev D Stanoeva M Velichkova A V Popova Institute of Biophysics and Biomedical Engineering Bulgarian Academy of Sciences Sofia Bulgaria Photosynthetic reactions taking place in thylakoid membranes


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  N 333 337 Tooke C 231 Topaloglu H 292 Topbas M 200 Topcu B 247 Topcu C 292 Topcu G 144 358 377 Topçu V 393 Topcu C 417 Topçuoglu C 193


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  L 266 Tsvetkova E 253 Tsyba L 362 Tsyganov D 158 Tsymbal D 165 Tüfekçi A R 241 358 Tufekci A R 296 Tufenkci H 139


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  Turan V 173 Turan Y 333 Turan C 411 Turano P 217 290 Türel S 329 341 Turhan T 193 242 Turhan Y 316 317 Turk S 373 Turkan A 219 Türkcan


id: cord-022940-atbjwpo5
type: CHEMICAL
entity:
  bread Triticum aestivum L durum Triticum turgidum ssp durum Desf wheat cultivars and einkorn Triticum monococcum ssp monococcum wheat


# bib

id: cord-000799-s70onyix
author: Wang, Ting
date: 2012-08-29
txt: ./txt/cord-000799-s70onyix.txt
cache: ./cache/cord-000799-s70onyix.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489700/
doi: 10.1186/1743-8977-9-35
summary:
  title: Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation OBJECTIVES: We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC) barrier integrity and enhanced cardiopulmonary dysfunction. We investigated the role of ROS and calpain in PM-induced pulmonary inflammation by examining protein leakage, white blood cell infiltration (inflammatory leukocytes), and the release of proinflammatory cytokines into BAL fluids ( Figure 5 ). These data represent the first evidence that calpain signaling, via calcium leakage from activated TRPM2 by ROS, plays a critical role in modulating endothelial cell barrier function, resulting in tight junction protein ZO-1 degradation (Additional file 1 Figure S7 ). Particulate matter induces endothelial cell intracellular oxidative stress, which leads to the activation of calpain, one of the major cytoskeletal regulators.

title:
  Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation

abstract:
  BACKGROUND: Exposure to particulate matter (PM) is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation. OBJECTIVES: We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC) barrier integrity and enhanced cardiopulmonary dysfunction. METHODS: Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER) in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm). Biochemical assessment of ROS generation and Ca(2+) mobilization were also measured. RESULTS: PM exposure induced tight junction protein Zona occludens-1 (ZO-1) relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin). N-acetyl-cysteine (NAC, 5 mM) reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2), in a ROS-dependent manner with subsequent activation of the Ca(2+)-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro. CONCLUSIONS: These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes.


id: cord-001347-ssrs0cwf
author: Michaelis, Martin
date: 2014-06-23
txt: ./txt/cord-001347-ssrs0cwf.txt
cache: ./cache/cord-001347-ssrs0cwf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080993/
doi: 10.1186/1756-0500-7-384
summary:
  title: Effects of flavonoid-induced oxidative stress on anti-H5N1 influenza a virus activity exerted by baicalein and biochanin A Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells. Next, we investigated whether the reduction of baicalein-or biochanin A-induced enhanced ROS levels in H5N1-infected A549 cells by NAC influences the antiviral effects of these flavonoids. Notably, NAC also inhibited baicalein-and biochanin A-induced oxidative stress in H5N1-infected primary human monocytederived macrophages but did not affect H5N1 replication in this cell type (Figure 3 ). These findings emphasise that flavonoids, a class of natural compounds known to exert anti-influenza effects [16] [17] [18] [19] 28] , induce a complex range of pharmacological actions by which they modify influenza A virus replication including highly pathogenic avian H5N1 strains. Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells

title:
  Effects of flavonoid-induced oxidative stress on anti-H5N1 influenza a virus activity exerted by baicalein and biochanin A

abstract:
  BACKGROUND: Different flavonoids are known to interfere with influenza A virus replication. Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells. Here, we investigated the effects of both compounds on H5N1-induced reactive oxygen species (ROS) formation and the role of ROS formation during H5N1 replication. FINDINGS: Baicalein and biochanin A enhanced H5N1-induced ROS formation in A549 cells and primary human monocyte-derived macrophages. Suppression of ROS formation induced by baicalein and biochanin A using the antioxidant N-acetyl-L-cysteine strongly increased the anti-H5N1 activity of both compounds in A549 cells but not in macrophages. CONCLUSIONS: These findings emphasise that flavonoids induce complex pharmacological actions some of which may interfere with H5N1 replication while others may support H5N1 replication. A more detailed understanding of these actions and the underlying structure-activity relationships is needed to design agents with optimised anti-H5N1 activity.


id: cord-001769-2sdg5ll7
author: Guo, Sheng
date: 2015-09-14
txt: ./txt/cord-001769-2sdg5ll7.txt
cache: ./cache/cord-001769-2sdg5ll7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569300/
doi: 10.1371/journal.ppat.1005155
summary:
  We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver. Further experiments show that mice deficient of p47 (phox), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1β secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. The hallmarks of MHV-3-induced FH in susceptible BALB/cJ and C57BL/6 mice include the appearance of liver sinusoidal thrombosis and hepatocellular necrosis, resulting from over expression of a virus-induced, monocyte/macrophage-specific procoagulant, fibrinogen-like protein-2 (FGL2).

title:
  The NLRP3 Inflammasome and IL-1β Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis

abstract:
  Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver. Whereas, the viral infection in IL-1β receptor-I deficient (IL-1R1 (-/-)) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality. IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45(+)Gr-1(high) neutrophil infiltration in the liver. The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation. Further experiments show that mice deficient of p47 (phox), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1β secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1β induction along with ameliorated hepatitis. Our results demonstrate that the ROS/NLRP3/IL-1β axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases.


id: cord-003841-7uaj9hmx
author: Desmonts de Lamache, D.
date: 2019-08-23
txt: ./txt/cord-003841-7uaj9hmx.txt
cache: ./cache/cord-003841-7uaj9hmx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707645/
doi: 10.1371/journal.pone.0221560
summary:
  The findings indicate that tulathromycin, in the absence of a direct anti-viral effect, is able to restore the phagocytic function and to attenuate the pro-inflammatory phenotype of PRRSV-infected monocyte-derived porcine macrophages. However, Immuno-modulating properties of Tulathromycin in PRRSV-infected porcine monocyte-derived macrophages PRRSV-induced IL-10 inhibition was abolished when the cells were pre-treated with tulathromycin at 2 and 12 hours post infection (Fig 6) . Another set of experiments assessed the effects of PRRSV, and of tulathromycin, on the nonopsonized and opsonized phagocytic functions of MDMs. PRRSV infection significantly Immuno-modulating properties of Tulathromycin in PRRSV-infected porcine monocyte-derived macrophages inhibited both phagocytic functions of the cells (Figs 10 and 11 ). The findings indicate that TUL inhibits PRRSV-induced inflammatory responses in porcine monocyte-derived macrophages and protects against the phagocytic impairment caused by the virus, in the absence of any direct anti-viral effects.

title:
  Immuno-modulating properties of Tulathromycin in porcine monocyte-derived macrophages infected with porcine reproductive and respiratory syndrome virus

abstract:
  Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus that grows in macrophages and causes acute pneumonia in pigs. PRRSV causes devastating losses to the porcine industry. However, due to its high antigenic variability and poorly understood immunopathogenesis, there is currently no effective vaccine or treatment to control PRRSV infection. The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics with immunomodulating properties for the treatment of the disease it causes. The macrolide antibiotic Tulathromycin (TUL) has been found to exhibit potent anti-inflammatory and immunomodulating properties in cattle and pigs. The aim of this study was to characterize the anti-viral and immunomodulating properties of TUL in PRRSV-infected porcine macrophages. Our findings indicate that blood monocyte-derived macrophages are readily infected by PRRSV and can be used as an effective cellular model to study PRRSV pathogenesis. TUL did not change intracellular or extracellular viral titers, not did it alter viral receptors (CD163 and CD169) expression on porcine macrophages. In contrast, TUL exhibited potent immunomodulating properties, which therefore occurred in the absence of any direct antiviral effects against PRRSV. TUL had an additive effect with PRRSV on the induction of macrophage apoptosis, and inhibited virus-induced necrosis. TUL significantly attenuated PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevented PRRSV inhibition of non-opsonized and opsonized phagocytic function. Together, these data demonstrate that TUL inhibits PRRSV-induced inflammatory responses in porcine macrophages and protects against the phagocytic impairment caused by the virus. Research in live pigs is warranted to assess the potential clinical benefits of this antibiotic in the context of virally induced inflammation and tissue injury.


id: cord-004508-ok3px98z
author: Armando, Federico
date: 2020-02-11
txt: ./txt/cord-004508-ok3px98z.txt
cache: ./cache/cord-004508-ok3px98z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077254/
doi: 10.3390/v12020200
summary:
  Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress. In a hypothesis-driven approach, an online available microarray data set of quadruplicates of non-infected DH82 and DH82Ond pi cells (ArrayExpress; http://www.ebi.ac.uk/arrayexpress; accession number E-MTAB-3942 [11, 44] ) was investigated for differentially expressed genes related to ROS production and scavenging, ER-stress and HIF-1α pathway, with a special focus on the angiogenic downstream targets of the latter.

title:
  Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1α Downstream Pathway Resulting in a Reduced Expression of VEGF-B In Vitro

abstract:
  Histiocytic sarcomas represent malignant tumors which require new treatment strategies. Canine distemper virus (CDV) is a promising candidate due to its oncolytic features reported in a canine histiocytic sarcoma cell line (DH82 cells). Interestingly, the underlying mechanism might include a dysregulation of angiogenesis. Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. Microarray data analysis, immunofluorescence for 8-hydroxyguanosine, superoxide dismutase 2 and catalase, and flow cytometry for oxidative burst displayed an increased oxidative stress in persistently CDV-infected DH82 cells (DH82Ond pi) compared to controls. The HIF-1α expression in DH82Ond pi increased, as demonstrated by Western blot, and showed an unexpected, often sub-membranous distribution, as shown by immunofluorescence and immunoelectron microscopy. Furthermore, microarray data analysis and immunofluorescence confirmed a reduced expression of VEGF-B in DH82Ond pi compared to controls. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress.


id: cord-005280-a23oy0sz
title: ROS and diseases: role in metabolism and energy supply
author: Yang, Shenshu
date: 2019-12-07
txt: ./txt/cord-005280-a23oy0sz.txt
cache: ./cache/cord-005280-a23oy0sz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089381/
doi: 10.1007/s11010-019-03667-9
summary:
  Although ROS play an important role in pathogen resistance and cellular signalling, they are also broadly recognized as harmful reactive particles to cell as they damage intracellular proteins, lipids and nucleic acids. The homeostasis of ROS plays an important role in reducing oxidative damage and fulfil energy demand. Relatively high levels of ROS may cause oxidative damage or induce apoptosis during immunological defences or pathological conditions. However, ROS themselves could activate extracellular signal-regulated kinase (ERK) by targeting proteins Gαi and Gα0 and protect cardiac cell from oxidative damage [18] . Apart from oxidative damage, ROS also serve as signalling molecules and play an important role in homeostasis, metabolism, growth and differentiation [3] . PGC-1α could protect neural cells from oxidative damage by reducing ROS level via antioxidative enzymes GPx1 and SOD2 [15] . ROS regulate vascular cell proliferation and apoptosis with their fundamental role in metabolism.

abstract:
  Researches dedicated to reactive oxygen species (ROS) had been performed for decades, yet the outcomes remain controversial. With the relentless effort of studies, researchers have explored the role of ROS in biosystem and various diseases. ROS are beneficial for biosystem presenting as signalling molecules and enhancing immunologic defence. However, they also have harmful effects such as causing tissue and organ damages. The results are controversial in studies focusing on ROS and ROS-related diseases by regulating ROS with inhibitors or promotors. These competing results hindered the process for further investigation of the specific mechanisms lying behind. The opinions presented in this review interpret the researches of ROS from a different dimension that might explain the competing results of ROS introduced so far from a broader perspective. This review brings a different thinking to researchers, with the neglected features and potentials of ROS, to relate their works with ROS and to explore the mechanisms between their subject and ROS.


id: cord-006230-xta38e7j
title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V.
author: nan
date: 2012-02-22
txt: ./txt/cord-006230-xta38e7j.txt
cache: ./cache/cord-006230-xta38e7j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100643/
doi: 10.1007/s00210-012-0736-0
abstract: nan
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.


id: cord-012495-r6nkdeaw
title: Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology
author: Bonora, Massimo
date: 2020-07-04
txt: ./txt/cord-012495-r6nkdeaw.txt
cache: ./cache/cord-012495-r6nkdeaw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408088/
doi: 10.3390/biom10070998
summary:
  Mitochondrial calcium overload and ROS levels can trigger either the activation of intrinsic apoptotic pathway (left side) through the recruitment of Bcl-2 family proteins at the mitochondria, or permeability transition pore complex (PTPC) formation which could lead to mitochondrial outer membrane permeabilization (MOMP), energetic imbalance, and subsequent release of proapoptotic cofactors from the inter membrane space, such as SMAC/DIABLO, CytC, and ENDOG (right side). MPT is associated with the opening of the mitochondrial permeability transition pore complex (PTPC), a voltage-dependent, high-conductance Mitochondrial calcium overload and ROS levels can trigger either the activation of intrinsic apoptotic pathway (left side) through the recruitment of Bcl-2 family proteins at the mitochondria, or permeability transition pore complex (PTPC) formation which could lead to mitochondrial outer membrane permeabilization (MOMP), energetic imbalance, and subsequent release of proapoptotic cofactors from the inter membrane space, such as SMAC/DIABLO, CytC, and ENDOG (right side).

abstract:
  Mitochondrial permeability transition (MPT) is the sudden loss in the permeability of the inner mitochondrial membrane (IMM) to low-molecular-weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse of the organelle. Thus, MPT can initiate outer-mitochondrial-membrane permeabilization (MOMP), promoting the activation of the apoptotic caspase cascade and caspase-independent cell-death mechanisms. The induction of MPT is mostly dependent on mitochondrial reactive oxygen species (ROS) and Ca(2+), but is also dependent on the metabolic stage of the affected cell and signaling events. Therefore, since its discovery in the late 1970s, the role of MPT in human pathology has been heavily investigated. Here, we summarize the most significant findings corroborating a role for MPT in the etiology of a spectrum of human diseases, including diseases characterized by acute or chronic loss of adult cells and those characterized by neoplastic initiation.


id: cord-013415-110b95cg
title: Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?
author: Aquino-Martinez, Ruben
date: 2020-10-09
txt: ./txt/cord-013415-110b95cg.txt
cache: ./cache/cord-013415-110b95cg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587987/
doi: 10.3390/ijms21207441
summary:
  Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. In contrast to transient DNA damage, persistent genomic lesions promote constitutive DNA damage signaling and cellular senescence, which is correlated with increased secretion of inflammatory signals [26, 30] In agreement with this observation, several studies have reported that premature senescence can also be induced by exposing human cells to subtoxic H 2 O 2 concentrations [31, 32] . As a consequence of chronological aging, the burden of senescent cells increases in different tissues in humans, mice, and other species, where they contribute to the development of chronic pathologies including arthritis, osteoporosis, Alzheimer''s disease, atherosclerosis, cancer, and diabetes [58, 59] Similar to other agerelated pathologies, the etiology of diabetes may be the result of the impact of different aging mechanism, including stem cell exhaustion, chronic low-grade inflammation, macromolecular damage, and cellular senescence.

abstract:
  The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease etiology. DNA damage-driven senescence is perhaps one of the most underappreciated delayed consequences of persistent Gram-negative bacterial infection and inflammation. Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. What happens to those healthy cells that reside in this harmful environment? Emerging evidence indicates that cells that survive irreparable genomic damage undergo cellular senescence, a crucial intermediate mechanism connecting DNA damage and the immune response. In this review, we hypothesize that sustained Gram-negative bacterial challenge, chronic inflammation itself, and the constant renewal of damaged tissues create a permissive environment for the abnormal accumulation of senescent cells. Based on emerging data we propose a model in which the dysfunctional presence of senescent cells may aggravate the initial immune reaction against pathogens. Further understanding of the role of senescent cells in periodontal disease pathogenesis may have clinical implications by providing more sophisticated therapeutic strategies to combat tissue destruction.


id: cord-014661-mrh2pbi6
title: Critical physiological and pathological functions of Forkhead Box O tumor suppressors
author: Dumitrascu, Georgiana R.
date: 2013-12-31
txt: ./txt/cord-014661-mrh2pbi6.txt
cache: ./cache/cord-014661-mrh2pbi6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941590/
doi: 10.15190/d.2013.5
summary:
  FOXO proteins are considered unique cellular targets, regulating a wide variety of critical cellular processes, such as: apoptosis, oxidative stress, DNA damage repair, cell cycle, stem cell proliferation and maintenance, metabolism, angiogenesis, vascular tone, cardiovascular development, fertility, immune response and neuronal survival 4, 20 . Hence, the FOXO transcription factors control the expression of a wide spectrum of genes that regulate essential physiological cellular processes, such as cell death/cell survival, cell cycle, cell proliferation, cell differentiation/development, angiogenesis, cell metabolism, stress response and stem cell maintenance 33,34,35,36,37,38 (Figure 2) . Moreover, the consensus FOXO recognition element (FRE) -(G/C)(T/A)AA(C/T)AA -which differs from that of other forkhead proteins, seems to have a very important role in both apoptotic pathways, since matching functional FRE sites have been identified in the promoters of FOXO target genes encoding Fas ligand (FasL), insulin like growth factorbinding protein 1 (IGFBP1), the apoptotic regulator Bcl-2 interacting mediator of cell death (Bim) and others 30 .

abstract:
  The Forkhead box, subclass O (FOXO) proteins are critical transcription factors, ubiquitously expressed in the human body. These proteins are characterized by a remarkable functional diversity, being involved in cell cycle arrest, apoptosis, oxidative detoxification, DNA damage repair, stem cell maintenance, cell differentiation, cell metabolism, angiogenesis, cardiac development, aging and others. In addition, FOXO have critical implications in both normal and cancer stem cell biology. New strategies to modulate FOXO expression and activity may now be developed since the discovery of novel FOXO regulators and non-coding RNAs (such as microRNAs) targeting FOXO transcription factors. This review focuses on physiological and pathological functions of FOXO proteins and on their action as fine regulators of cell fate and context-dependent cell decisions. A better understanding of the structure and critical functions of FOXO transcription factors and tumor suppressors may contribute to the development of novel therapies for cancer and other diseases.


id: cord-017817-ztp7w9yh
title: Cell-Autonomous (Cell-Intrinsic) Stress Responses
author: Land, Walter Gottlieb
date: 2018-03-28
txt: ./txt/cord-017817-ztp7w9yh.txt
cache: ./cache/cord-017817-ztp7w9yh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122488/
doi: 10.1007/978-3-319-78655-1_18
summary:
  Autophagy is an evolutionarily highly conserved self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components such as defective/damaged or redundant organelles or protein aggregates are delivered to the lysosome for recycling and degradation. More recent studies then revealed that these transcription factors, notably Nrf2, are activated by Keap1 as the primary negative regulator of Nrf2, that is, a molecule that simultaneously operates as a sensor protein able to perceive dyshomeostatic Subclass IIC-4 DAMPs, for example, in terms of redox changes reflecting electrophilic stress. Strikingly, a complex relationship reportedly exists between autophagy and DAMPs in cellular adaption to stress and injury and cell death characterized by a crosstalk between autophagy induction and secretion or release of DAMPs. In fact, growing evidence indicates that autophagic mechanisms are involved in regulating release and degradation of DAMPs including CALR, HMGB1, ATP, and DNA in several cell types [37, 148, 175] .

abstract:
  In this chapter, the role of cell-intrinsic stress responses is examined which include autophagic processes, the oxidative stress response, the heat shock response, the unfolded proteins response, and the DNA damage response. Autophagy (macroautophagy, microautophagy, and chaperone-mediated autophagy) is a self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components are delivered to the lysosome for recycling and degradation. The oxidative stress response is directed against any oxidative stress and is mediated by antioxidative defense systems including antioxidant enzymes such as superoxide dismutase, detoxifying enzymes such as glutathione peroxidase, and energy-dependent efflux pumps. The heat shock response is induced upon exposure of cells to any stress condition and characterized by emission of heat shock proteins which operate as DAMPs to maintain and restore homeostasis. The unfolded protein response is induced by any stress of the endoplasmic reticulum that is perceived by three sensor molecules. Under remediable endoplasmic reticulum stress conditions, the sensors trigger signalling pathways to resolve this stress. However, in severe irremediable endoplasmic reticulum stress, the unfolded protein response may lead to pro-inflammatory and pro-apoptotic responses resulting in regulated cell death. Finally, the DNA damage response is induced by any DNA damage that occurs in a variety of exogenous and endogenous conditions. When successful, this stress response leads to DNA repair and is associated with the emission of various DAMPs which contribute to restoration of homeostasis. When unsuccessful, the DNA damage response, like the unsuccessful unfolded protein response, can result in regulated cell death, either in form of apoptosis or necrosis. Together, the ultimate goal of all the stress responses is to maintain cellular homeostasis and ensure cell integrity. When they fail, the incidence of regulated cell death is frequently observed.


id: cord-020646-s7eopu9y
title: Die Pathophysiologie der Entzündung
author: nan
date: 2005
txt: ./txt/cord-020646-s7eopu9y.txt
cache: ./cache/cord-020646-s7eopu9y.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143866/
doi: 10.1007/3-211-29899-1_2
abstract: nan
summary:
  Die Wirkung des Histamins auf Zielzellen erfolgt über spezifi sche Rezeptoren, von denen zwei Arten bekannt und gut studiert sind. Bei plötzlicher Aufhebung der Rezeptorblockade nach Ende einer Therapie sind die betroffenen Zellen mit einer hohen Rezeptorzahl bestückt und reagieren folglich auf Histamin verstärkt, was zum massiven Wiederauftreten der Krankheitssymptomatik führen kann (sog. Disponierte Personen, die als "Atopiker" bezeichnet werden, reagieren auf gewisse Antigene (AG) mit der Bildung spezifi scher Antikörper (AK) vom IgE-Typ. Die atopische Veranlagung ist angeboren, tritt oft familiär auf und zeigt eine Konvergenz mit gewissen MHC I Typen. Dem PAF wird heute eine wesentliche Rolle beim Pathomechanismus des Asthma bronchiale und der COPD zugeschrieben, wobei die Wirkung auch indirekt, nämlich über eine Potenzierung anderer Mediatoren wie LT, PG, Histamin zu laufen scheint. Diese Bindung ist der Mechanismus, über den die Zelle ein Partikel erkennt und von Material unterscheidet, das nicht phagozytiert werden soll, und der den Phagozytosereiz auslöst.


id: cord-022940-atbjwpo5
title: Poster Sessions
author: nan
date: 2016-09-07
txt: ./txt/cord-022940-atbjwpo5.txt
cache: ./cache/cord-022940-atbjwpo5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164006/
doi: 10.1111/febs.13808
abstract: nan
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.


id: cord-032561-x3qbqy69
title: Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment
author: Liu, Gengqi
date: 2020-09-02
txt: ./txt/cord-032561-x3qbqy69.txt
cache: ./cache/cord-032561-x3qbqy69.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504550/
doi: 10.3390/ijms21176380
summary:
  demonstrated that nanodrug carriers with diselenides could release more drugs using poly (ester carbamate) triblock copolymers (PAUR-Se-Se) with Se-Se bonds compared with poly (ester carbamate) triblock copolymers (PAUR-S-S) [54, 55] Thioether Selenium Tellurium Besides the development of drug delivery systems, pH-responsive systems can also be used for tumor detection and image-guided surgery [46] . demonstrated that nanodrug carriers with diselenides could release more drugs using poly (ester carbamate) triblock copolymers (PAUR-Se-Se) with Se-Se bonds compared with poly (ester carbamate) triblock copolymers (PAUR-S-S) [65] PBA/PBE Besides the development of drug delivery systems, pH-responsive systems can also be used for tumor detection and image-guided surgery [46] . Therefore, pH responsive system can be combined with other stimulus conditions such as light, redox, enzymes and others with the aim of improved selectivity for drug release in diseased tissues [47, 48] . In addition to photothermal therapy and PDT, light-responsive strategies have also been applied in the design of prodrug systems and drug delivery carriers.

abstract:
  Stimulus-responsive drug delivery systems generally aim to release the active pharmaceutical ingredient (API) in response to specific conditions and have recently been explored for disease treatments. These approaches can also be extended to molecular imaging to report on disease diagnosis and management. The stimuli used for activation are based on differences between the environment of the diseased or targeted sites, and normal tissues. Endogenous stimuli include pH, redox reactions, enzymatic activity, temperature and others. Exogenous site-specific stimuli include the use of magnetic fields, light, ultrasound and others. These endogenous or exogenous stimuli lead to structural changes or cleavage of the cargo carrier, leading to release of the API. A wide variety of stimulus-responsive systems have been developed—responsive to both a single stimulus or multiple stimuli—and represent a theranostic tool for disease treatment. In this review, stimuli commonly used in the development of theranostic nanoplatforms are enumerated. An emphasis on chemical structure and property relationships is provided, aiming to focus on insights for the design of stimulus-responsive delivery systems. Several examples of theranostic applications of these stimulus-responsive nanomedicines are discussed.


id: cord-034294-ti1cc24m
title: Progress in the mechanism and targeted drug therapy for COPD
author: Wang, Cuixue
date: 2020-10-27
txt: ./txt/cord-034294-ti1cc24m.txt
cache: ./cache/cord-034294-ti1cc24m.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588592/
doi: 10.1038/s41392-020-00345-x
summary:
  Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways. EPAC and PKA inhibit the human airway smooth muscle induced by a cigarette smoke extract (CSE) by blocking the activation of the NF-κB and ERK, respectively, and by releasing neutrophil chemokine IL-8, which together exert anti-inflammatory effects. 101 In COPD, increases in cAMP levels, activation of PKA and enhanced protein phosphorylation have the potential to reduce inflammation and immunomodulation, relax airway smooth muscle, inhibit chemotaxis and abnormal release of inflammatory and cytotoxic mediators, and reduce proliferation and migration of inflammatory cells. 135 The PI3K/Akt signalling pathway plays an important role in COPD by regulating inflammatory cell activation, inflammatory mediator release and airway remodelling.

abstract:
  Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow. The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression. Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs. Among these new drugs, we focussed on thioredoxin (Trx). Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways. The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses. In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF). Taken together, these findings suggest that Trx may be the ideal drug for treating COPD.


id: cord-034321-ohjik0pf
title: NETosis: Molecular Mechanisms, Role in Physiology and Pathology
author: Vorobjeva, N. V.
date: 2020-10-27
txt: ./txt/cord-034321-ohjik0pf.txt
cache: ./cache/cord-034321-ohjik0pf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590568/
doi: 10.1134/s0006297920100065
summary:
  NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. NETosis includes release of the granule components into the cytosol, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope, as well as formation of pores in the plasma membrane. 1178 Abbreviations: ARDS, acute respiratory distress syndrome; CGD, chronic granulomatous disease; COPD, chronic obstructive pulmonary disease; GSDMD, gasdermin D; LPS, lipopolysaccharide of the bacterial wall; MPO, myeloper oxidase; mPTP, nonselective mitochondrial permeability tran sition pore; NE, neutrophil elastase; NETs, Neutrophil Extra cellular Traps; PCD, programmed cell death; PKC, protein kinase C; PMA, phorbol 12 myristate 13 acetate; ROS, reac tive oxygen species. At the same time, we also showed that in neutrophils isolated from the blood of patients with X linked CGD formation of NETs in response to A23187 depended on the enhanced gener ation of mtROS without participation of NADPH oxi dase [16] .

abstract:
  NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. Various pathogens, antibodies and immune complexes, cytokines, microcrystals, and other physiological stimuli can cause NETosis. Induction of NETosis depends on reactive oxygen species (ROS), the main source of which is NADPH oxidase. Activation of NADPH oxidase depends on increase in the concentration of Ca(2+) in the cytoplasm and in some cases on the generation of ROS in mitochondria. NETosis includes release of the granule components into the cytosol, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope, as well as formation of pores in the plasma membrane. In this review, basic mechanisms of NETosis, as well as its role in the pathogenesis of some diseases including COVID-19 are discussed.


id: cord-035015-slgywe0c
title: SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing
author: Nunn, Alistair V. W.
date: 2020-11-09
txt: ./txt/cord-035015-slgywe0c.txt
cache: ./cache/cord-035015-slgywe0c.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649575/
doi: 10.1186/s12979-020-00204-x
summary:
  Data is now showing that COVID-19 patients do have populations of T-cells displaying mitochondrial dysfunction, as well as altered mitochondrial markers in monocyteshinting that immune-metabolic phenotyping could be used to understand disease pathogenesis and possible treatments; this could include targeting mitochondria [32] . The underlying aetiology for "inflammaging" has long thought to be associated with mitochondrial dysfunction as suggested by Nick Lane in 2003 in his "double agent" theory [5] , and is now receiving renewed interest, for instance, in how decreasing mitochondrial function can reduce T-cell function and enhance immune senescence, as mitochondria are pivotal in metabolic reprogramming towards the Warburg effect [40] . Furthermore, as evidence indicates that many viruses, which most likely include SARs-CoV-2, modulate bioenergetics and redox in both the immune system and other cells they infect to enhance their own replication, they could potentially induce excessive stress in these systems if their mitochondria are already sub-optimally functional.

abstract:
  Infection with SARs-COV-2 displays increasing fatality with age and underlying co-morbidity, in particular, with markers of the metabolic syndrome and diabetes, which seems to be associated with a “cytokine storm” and an altered immune response. This suggests that a key contributory factor could be immunosenescence that is both age-related and lifestyle-induced. As the immune system itself is heavily reliant on mitochondrial function, then maintaining a healthy mitochondrial system may play a key role in resisting the virus, both directly, and indirectly by ensuring a good vaccine response. Furthermore, as viruses in general, and quite possibly this new virus, have also evolved to modulate immunometabolism and thus mitochondrial function to ensure their replication, this could further stress cellular bioenergetics. Unlike most sedentary modern humans, one of the natural hosts for the virus, the bat, has to “exercise” regularly to find food, which continually provides a powerful adaptive stimulus to maintain functional muscle and mitochondria. In effect the bat is exposed to regular hormetic stimuli, which could provide clues on how to resist this virus. In this paper we review the data that might support the idea that mitochondrial health, induced by a healthy lifestyle, could be a key factor in resisting the virus, and for those people who are perhaps not in optimal health, treatments that could support mitochondrial function might be pivotal to their long-term recovery.


id: cord-048478-ftlb5b95
title: Apoptotic signals induce specific degradation of ribosomal RNA in yeast
author: Mroczek, Seweryn
date: 2008-04-01
txt: ./txt/cord-048478-ftlb5b95.txt
cache: ./cache/cord-048478-ftlb5b95.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2396418/
doi: 10.1093/nar/gkm1100
summary:
  One striking characteristic, which accompanies apoptosis in both vertebrates and yeast, is a fragmentation of cellular DNA and mammalian apoptosis is often associated with degradation of different RNAs. We show that in yeast exposed to stimuli known to induce apoptosis, such as hydrogen peroxide, acetic acid, hyperosmotic stress and ageing, two large subunit ribosomal RNAs, 25S and 5.8S, became extensively degraded with accumulation of specific intermediates that differ slightly depending on cell death conditions. For example, in metazoans the programmed cell death (PCD) called apoptosis, in addition to irreversible DNA damage, which is considered an apoptotic hallmark (3) , also involves specific cleavage of several RNA species, including 28S rRNA, U1 snRNA or Ro RNP-associated Y RNAs (4) . Together, this strongly suggests that rRNA degradation observed in apoptotic and oxidative stress conditions is not simply a result of cell death but is produced in the process that requires enzymatic activity and functional cellular machinery.

abstract:
  Organisms exposed to reactive oxygen species, generated endogenously during respiration or by environmental conditions, undergo oxidative stress. Stress response can either repair the damage or activate one of the programmed cell death (PCD) mechanisms, for example apoptosis, and finally end in cell death. One striking characteristic, which accompanies apoptosis in both vertebrates and yeast, is a fragmentation of cellular DNA and mammalian apoptosis is often associated with degradation of different RNAs. We show that in yeast exposed to stimuli known to induce apoptosis, such as hydrogen peroxide, acetic acid, hyperosmotic stress and ageing, two large subunit ribosomal RNAs, 25S and 5.8S, became extensively degraded with accumulation of specific intermediates that differ slightly depending on cell death conditions. This process is most likely endonucleolytic, is correlated with stress response, and depends on the mitochondrial respiratory status: rRNA is less susceptible to degradation in respiring cells with functional defence against oxidative stress. In addition, RNA fragmentation is independent of two yeast apoptotic factors, metacaspase Yca1 and apoptosis-inducing factor Aif1, but it relies on the apoptotic chromatin condensation induced by histone H2B modifications. These data describe a novel phenotype for certain stress- and ageing-related PCD pathways in yeast.


id: cord-102808-c7ajfvt5
author: Sundqvist, Martina
date: 2020-05-01
txt: ./txt/cord-102808-c7ajfvt5.txt
cache: ./cache/cord-102808-c7ajfvt5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.04.30.070011
doi: 10.1101/2020.04.30.070011
summary:
  The formyl peptide receptor 2 (FPR2), belonging to the family of G protein-coupled receptors (GPCRs), regulates directional neutrophil migration (chemotaxis), granule secretion (degranulation), formation of F-actin filaments (through polymerization of G-actin), and activation of the reactive oxygen species (ROS) producing NADPH-oxidase [3, 5, 6] . The fact that F2Pal10 and Cmp 14 cannot induce -arrestin recruitment at these concentrations ([9-11], Fig 2A) , strongly suggests that the priming effect of Barbadin on FPR2-mediated ROS production is independent of the ability of the activating agonist to recruit -arrestin. Collectively, these results suggest that Barbadin primes neutrophils in their response to FPR2 agonists, and the increased NADPH-oxidase activation is regulated independently of FPR2 internalization and FPR2-induced -arrestin recruitment. Barbadin was added to WKYMVM-activated neutrophils at a time point when ROS production had returned to a background level; interestingly, these FPR2-desensitized cells could be resensitized to produce ROS also by Barbadin, similar to the effect of latrunculin A ( Fig 5A) .

title:
  Barbadin selectively modulates FPR2-mediated neutrophil functions independent of receptor endocytosis

abstract:
  Formyl peptide receptor 2 (FPR2), a member of the family of G protein-coupled receptors (GPCRs), mediates neutrophil migration, a response that has been linked to β-arrestin recruitment. β-Arrestin regulates GPCR endocytosis and can also elicit non-canonical receptor signaling. To determine the poorly understood role of β-arrestin in FPR2 endocytosis and in NADPH-oxidase activation in neutrophils, Barbadin was used as a research tool in this study. Barbadin has been shown to bind the clathrin adaptor protein (AP2) and thereby prevent β- arrestin/AP2 interaction and β-arrestin-mediated GPCR endocytosis. In agreement with this, AP2/β-arrestin interaction induced by an FPR2-specific agonist was inhibited by Barbadin. Unexpectedly, however, Barbadin did not inhibit FPR2 endocytosis, indicating that a mechanism independent of β-arrestin/AP2 interaction may sustain FPR2 endocytosis. This was confirmed by the fact, that FPR2 also underwent agonist-promoted endocytosis in β-arrestin deficient cells, albeit at a diminished level as compared to wild type cells. Dissection of the Barbadin effects on FPR2-mediated neutrophil functions including NADPH-oxidase activation mediated release of reactive oxygen species (ROS) and chemotaxis reveled that Barbadin had no effect on chemotactic migration whereas the release of ROS was potentiated/primed. The effect of Barbadin on ROS production was reversible, independent of β-arrestin recruitment, and similar to that induced by latrunculin A. Taken together, our data demonstrate that endocytic uptake of FPR2 occurs independently of β-arrestin, while Barbadin selectively augments FPR2-mediated neutrophil ROS production independently of receptor endocytosis. Given that Barbadin binds to AP2 and prevents the AP2/β-arrestin interaction, our results indicate a role for AP2 in FPR2-mediated ROS release from human neutrophils.


id: cord-257514-gw9xnb4x
title: Hydrogen: A Novel Option in Human Disease Treatment
author: Yang, Mengling
date: 2020-09-05
txt: ./txt/cord-257514-gw9xnb4x.txt
cache: ./cache/cord-257514-gw9xnb4x.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1155/2020/8384742
doi: 10.1155/2020/8384742
summary:
  H(2) gas may regulate the anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (apoptosis, autophagy, pyroptosis, ferroptosis, and circadian clock, among others) and has therapeutic potential for many systemic diseases. found that HW inhibited cardiomyocyte apoptosis by activating the PI3K/AKT and JAK2-STAT3 signaling pathways and can also reduce the level of oxidative stress in myocardial tissue by upregulating the expression of the nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway, which alleviated I/R injury in isolated rat hearts [39, 40, 91] . Effects of hydrogen-rich water on the PI3K/AKT signaling pathway in rats with myocardial 12 Oxidative Medicine and Cellular Longevity ischemia-reperfusion injury Effects of hydrogen-rich saline on early acute kidney injury in severely burned rats by suppressing oxidative stress induced apoptosis and inflammation

abstract:
  H(2) has shown anti-inflammatory and antioxidant ability in many clinical trials, and its application is recommended in the latest Chinese novel coronavirus pneumonia (NCP) treatment guidelines. Clinical experiments have revealed the surprising finding that H(2) gas may protect the lungs and extrapulmonary organs from pathological stimuli in NCP patients. The potential mechanisms underlying the action of H(2) gas are not clear. H(2) gas may regulate the anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (apoptosis, autophagy, pyroptosis, ferroptosis, and circadian clock, among others) and has therapeutic potential for many systemic diseases. This paper reviews the basic research and the latest clinical applications of H(2) gas in multiorgan system diseases to establish strategies for the clinical treatment for various diseases.


id: cord-260348-83ftjqev
title: Cepharanthine and Curcumin inhibited mitochondrial apoptosis induced by PCV2
author: Xu, Yinlan
date: 2020-09-18
txt: ./txt/cord-260348-83ftjqev.txt
cache: ./cache/cord-260348-83ftjqev.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32948186/
doi: 10.1186/s12917-020-02568-0
summary:
  The results of qPCR and Western blot showed that, compared with the PCV2 infected group, the expression of Cap in Paeonol (0.4 mg/mL and 0.2 mg/mL), Cepharanthine (0.003 mg/mL, 0.0015 mg/mL and 0.00075 mg/mL) and Curcumin (0.02 mg/mL, 0.001 mg/mL and 0.005 mg/mL) treated groups were significantly lowered in a dose-dependent manner. The results of Annexin V-FITC/PI, JC-1, Western blot and ROS analysis showed that the expression of cleaved caspase-3 and Bax were up-regulated Bcl-2 was down-regulated in Cepharanthine or Curcumin treated groups, while ROS and MMP value were decreased at different degrees and the apoptosis rate was reduced. The results showed that Compared to the PCV2-infected group, the cell apoptosis rates were significantly decreased in the group treated with Cepharanthine, Curcumin or Ribavirin, demonstrating a dose-dependent response except the group of 0.005 mg/mL Paeonol (P < 0.05) ( Fig. 3a and b).

abstract:
  BACKGROUND: Porcine circovirus type 2 (PCV2) is an immunosuppressive pathogen with high prevalence rate in pig farms. It has caused serious economic losses to the global pig industry. Due to the rapid mutation of PCV2 strain and co-infection of different genotypes, vaccination could not eradicate the infection of PCV2. It is necessary to screen and develop effective new compounds and explore their anti-apoptotic mechanism. The 13 natural compounds were purchased, with a clear plant origin, chemical structure and content and specific biological activities. RESULTS: The maximum no-cytotoxic concentration (MNTC) and 50% cytotoxic concentration (CC(50)) of 13 tested compounds were obtained by the cytopathologic effect (CPE) assay and (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in PK-15 cells. The results of qPCR and Western blot showed that, compared with the PCV2 infected group, the expression of Cap in Paeonol (0.4 mg/mL and 0.2 mg/mL), Cepharanthine (0.003 mg/mL, 0.0015 mg/mL and 0.00075 mg/mL) and Curcumin (0.02 mg/mL, 0.001 mg/mL and 0.005 mg/mL) treated groups were significantly lowered in a dose-dependent manner. The results of Annexin V-FITC/PI, JC-1, Western blot and ROS analysis showed that the expression of cleaved caspase-3 and Bax were up-regulated Bcl-2 was down-regulated in Cepharanthine or Curcumin treated groups, while ROS and MMP value were decreased at different degrees and the apoptosis rate was reduced. In this study, Ribavirin was used as a positive control. CONCLUSIONS: Paeonol, Cepharanthine and Curcumin have significant antiviral effect. And the PCV2-induced Mitochondrial apoptosis was mainly remitted by Cepharanthine and Curcumin.


id: cord-262759-ec2c25q3
author: Hsieh, Yi-Ting
date: 2013-11-04
txt: ./txt/cord-262759-ec2c25q3.txt
cache: ./cache/cord-262759-ec2c25q3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24223971/
doi: 10.1371/journal.pone.0079566
summary:
  The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. We hypothesized that G6PD-deficient cells are less tolerant to oxidative stress upon bacterial infection, leading to the accumulation of more intracellular ROS when compared to the control scramble cells. To determine whether the reduced ROS accumulation and apoptotic activity, particularly in G6PD-deficient cells, was due to deceased αhemolysin expression upon VRSA infection in the presence of vancomycin, the production of intracellular ROS and cell apoptosis when the α-hemolysin inhibitor Oroxylin A was added to the media was quantified by flow cytometry. Our results presented here indicate that expression of active caspase-9, as well as the downstream caspase-3, was much higher in G6PD-deficient cells than in control scramble cells upon VRSA infection, suggesting that mitochondrial dysfunction may be the major cause of the increase in cell apoptosis (Figure 4) .

title:
  Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus

abstract:
  Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells.


id: cord-268122-74nj66vb
title: NAD(+) metabolism: pathophysiologic mechanisms and therapeutic potential
author: Xie, Na
date: 2020-10-07
txt: ./txt/cord-268122-74nj66vb.txt
cache: ./cache/cord-268122-74nj66vb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41392-020-00311-7
doi: 10.1038/s41392-020-00311-7
summary:
  The NAD + decline during normal aging results in oxidative damage, metabolic disorder, circadian rhythm abnormalities, and mitochondrial dysfunction through regulating signaling pathways, such as p53, NF-κB, PGC-1α and HIF-1α, by sirtuins and PARPs. NAD + and its metabolites function as crucial regulators to maintain cellular redox homeostasis through replenishing the reducing power or modulating the activity of NAD + -consuming enzymes including sirtuins and PARPs. However, disequilibrium of NAD + metabolism could disturb physiological processes, including mitochondria function, circadian rhythm, inflammation, DNA repair and metabolism, leading to aging-associated dysfunction and cancer. c The deduced NAD + levels in kidney are attributed to the decreased expression of enzymes in NAD + de novo synthesis and increased consumption by DNA damage activated PARPs. NAD + depletion inhibits the SIRT1/PGC1α mediated mitochondrial quality control, ATP production and NAD + de novo biosynthesis.

abstract:
  Nicotinamide adenine dinucleotide (NAD(+)) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD(+) on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD(+)-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP(+). Prolonged disequilibrium of NAD(+) metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD(+)-regulated physiological responses to stresses, the contribution of NAD(+) deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.


id: cord-268527-wbfnhedy
title: Transient hyperglycosylation of rhodopsin with galactose
author: Smith, Sylvia B.
date: 1991-10-31
txt: ./txt/cord-268527-wbfnhedy.txt
cache: ./cache/cord-268527-wbfnhedy.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/001448359190170J
doi: 10.1016/0014-4835(91)90170-j
summary:
  Following subcellular fractionation of retinas, ConA purified rhodopsin from ROS was applied to one of two additional lectin columns: Ricinus communis agglutinin (RCA) or Griffonia simplicifolia I (GSA). To radiolabel existing galactose moieties on rhodopsin, bovine ROS purified by a discontinuous sucrose density gradient procedure, were subjected to enzymatic treatment with galactose oxidase followed by a reduction with tritium labeled sodium borohydride. In this method, ConA purified rhodopsin or in some cases the clarified extract of ROS from six rat retinas labeled with [35S]methionine was applied to columns of either Ricinus communis agglutinin I (RCA) or GrifSonia simplicijolia I (GSA), specific for P-linked or a-linked galactose residues, respectively. Rats injected intravitreally with [35S]methionine were maintained in darkness for 2 hr at which time 12 retinas were collected for subcellular fractionation and rhodopsin purification by ConA sepharose chromatography.

abstract:
  Abstract Rhodopsin's oligosaccharide chains contain predominantly two types of sugar residues: mannose and N-acetylglucosamine. In the present work, bovine and rat rhodopsin were analysed biochemically for the presence of a third sugar, galactose. Treatment of bovine rod outer segments (ROS) with galactose oxidase followed by reduction with tritium-labeled sodium borohydride revealed the presence of existing molecules of galactose on rhodopsin. Rats injected intravitreally with [3H]galactose and [14C]leucine and maintained in darkness were killed 1 hr, 6 hr, 1, 3, or 5 days following the injection. Retinas were collected for subcellular fractionation and rhodopsin from each of the fractions was purified by ConA sepharose chromatography and SDS-PAGE. During the first 6 hr, galactose selectively labeled rhodopsin in the Golgi-enriched fraction resulting in increased [3H] [14C] ratios in both Golgi and ROS. The data suggested that trimming was occurring at the transition from Golgi to ROS. Furthermore, a decrease in isotope ratio in the ROS between 6 hr and 1 day suggested further trimming of rhodopsin after membrane assembly in the ROS. Additional in vivo experiments demonstrated existing molecules of galactose on rhodopsin's oligosaccharide chain using lectin affinity chromatography. Rats injected intravitreally with [35S]methionine were dark-adapted for 2 hr. Following subcellular fractionation of retinas, ConA purified rhodopsin from ROS was applied to one of two additional lectin columns: Ricinus communis agglutinin (RCA) or Griffonia simplicifolia I (GSA). Eight to nine per cent of the labeled rhodopsin was bound to and eluted from RCA, whereas none bound to GSA, indicating the presence of a β-galactoside. The RCA agarose eluted protein co-electrophoresed with a rhodopsin standard and was light sensitive. Galactose was shown to be the terminal sugar on this subset of rhodopsin and was not capped by neuraminic acid. Binding of rhodopsin's oligosaccharide to RCA was abolished by pre-treatment with β-galactosidase. Decreased binding of rhodopsin to RCA was observed following intravitreal injection of castanospermine but not swainsonine. Of those two inhibitors of glycoprotein trimming, only castanospermine would be expected to prevent the addition of galactose to the oligosaccharide. The association of galactose with rat rhodopsin appeared to be a transient one. At 2 hr, 8–9% of rhodopsin contained galactose, at 6 hr only 2·2% had galactose and by 24 hr less than 1% did. The galactose was trimmed from rhodopsin's oligosaccharide presumably after its role was complete. Separation of rhodopsin of the plasma membranes from rhodopsin of discs indicated that 75% of the galactose-containing rhodopsin was in the plasma membrane and only 25% was in the discs. These findings suggested a possible role for galactose in new disc formation with subsequent removal after the discs are sealed.


id: cord-271939-m1ko4yal
title: Pursuing the Elixir of Life: In Vivo Antioxidative Effects of Manganosalen Complexes
author: Rouco, Lara
date: 2020-08-10
txt: ./txt/cord-271939-m1ko4yal.txt
cache: ./cache/cord-271939-m1ko4yal.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/antiox9080727
doi: 10.3390/antiox9080727
summary:
  Thus, manganosalen complexes have been shown to exhibit superoxide dismutase, catalase, and glutathione peroxidase activities, and they could potentially facilitate the scavenging of excess reactive oxygen species (ROS), thereby restoring the redox balance in damaged cells and organs. Manganosalen complexes exhibit high SOD, catalase, and peroxidase activities, which has led to their development as catalytic antioxidants [6] [7] [8] [9] [10] 13, [18] [19] [20] [21] 23] , a term used for all cases in which one single molecule of catalyst induces the detoxification of numerous ROS molecules. This manganese complex and the cyclic analogue EUK-207 were used in a study with C57BL/6N Sim middle-age mice [105] , which usually exhibit a dramatic decrease in learning and memory function between 8 and 11 months of age, associated with oxidative protein damage in the brain [106] . Salen-manganese complexes for controlling ROS damage: Neuroprotective effects, antioxidant activity and kinetic studies

abstract:
  Manganosalen complexes are coordination compounds that possess a chelating salen-type ligand, a class of bis-Schiff bases obtained by condensation of salicylaldehyde and a diamine. They may act as catalytic antioxidants mimicking both the structure and the reactivity of the native antioxidant enzymes active site. Thus, manganosalen complexes have been shown to exhibit superoxide dismutase, catalase, and glutathione peroxidase activities, and they could potentially facilitate the scavenging of excess reactive oxygen species (ROS), thereby restoring the redox balance in damaged cells and organs. Initial catalytic studies compared the potency of these compounds as antioxidants in terms of rate constants of the chemical reactivity against ROS, giving catalytic values approaching and even exceeding that of the native antioxidative enzymes. Although most of these catalytic studies lack of biological relevance, subsequent in vitro studies have confirmed the efficiency of many manganosalen complexes in oxidative stress models. These synthetic catalytic scavengers, cheaper than natural antioxidants, have accordingly attracted intensive attention for the therapy of ROS-mediated injuries. The aim of this review is to focus on in vivo studies performed on manganosalen complexes and their activity on the treatment of several pathological disorders associated with oxidative damage. These disorders, ranging from the prevention of fetal malformations to the extension of lifespan, include neurodegenerative, inflammatory, and cardiovascular diseases; tissue injury; and other damages related to the liver, kidney, or lungs.


id: cord-273093-u79r80ip
title: Tissue damage from neutrophil-induced oxidative stress in COVID-19
author: Laforge, Mireille
date: 2020-07-29
txt: ./txt/cord-273093-u79r80ip.txt
cache: ./cache/cord-273093-u79r80ip.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41577-020-0407-1
doi: 10.1038/s41577-020-0407-1
summary:
  The high neutrophil to lymphocyte ratio observed in critically ill patients with COVID-19 is associated with excessive levels of reactive oxygen species (ROS), which promote a cascade of biological events that drive pathological host responses. By producing excessive ROS, deregulated neutrophils can spread a local inflammatory response so that it becomes systemic, which explains why they have been involved The high neutrophil to lymphocyte ratio observed in critically ill patients with COVID-19 is associated with excessive levels of reactive oxygen species (ROS), which promote a cascade of biological events that drive pathological host responses. ROS induce tissue damage, thrombosis and red blood cell dysfunction, which contribute to COVID-19 disease severity. ROS induce tissue damage, thrombosis and red blood cell dysfunction, which contribute to COVID-19 disease severity. In conclusion, the presence of oxidative stress markers (for example, lipid peroxidation, rTEM and a high neutrophil to lymphocyte ratio) in patients with COVID-19 may help to identify high-risk individuals early in the course of the disease and prevent their sudden deterioration.

abstract:
  The high neutrophil to lymphocyte ratio observed in critically ill patients with COVID-19 is associated with excessive levels of reactive oxygen species (ROS), which promote a cascade of biological events that drive pathological host responses. ROS induce tissue damage, thrombosis and red blood cell dysfunction, which contribute to COVID-19 disease severity. We suggest that free radical scavengers could be beneficial for the most vulnerable patients.


id: cord-273992-xddikzxs
author: Wiseman, A.
date: 2004-11-10
txt: ./txt/cord-273992-xddikzxs.txt
cache: ./cache/cord-273992-xddikzxs.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15613000/
doi: 10.1111/j.1472-765x.2004.01624.x
summary:
  The main impact of the study is that the utilization of genetically modified (GM) yeast produced by recombinant DNA technology genomic strategies could circumvent the bioprocessing problems that otherwise result from the bioprocess perturbations: this is as a result of oxidative stress caused by ROS, which is avoidable by deployment of appropriate antioxidants such as vitamins E, C and D (and antioxidant proteins and enzymes often of microbial origin via recombinant DNA technology). Catalases ( Table 3 ) in yeasts and other micro-organisms (Antioxidants such as vitamins E and C chain terminate the formation of membrane-degrading ROS) relates to more than just structural damage that is sometimes obvious and predictable: functional damage may also follow. Avoidance biostrategies against ROS and RSS in many oxidatively stressed bioprocesses that utilise yeasts (and other micro-organisms) are essential where human therapeutic proteins are expected to be produced in high yield.

title:
  Avoidance of oxidative‐stress perturbation in yeast bioprocesses by proteomic and genomic biostrategies?

abstract:
  Aims: Bioprocess oxidative stress caused by many reactive oxygen species (ROS) can lead to largely irreversible perturbation of yeast bioprocesses. These include the production of proteins derived from recombinant DNA yeast technology (aerobically grown Saccharomyces cerevisiae). These proteins include rennin, amyloglucosidases (glucamylases), interferons, interleukins, insulin, monoclonal antibodies, tissue plasminogen activators (t‐PA), sexually transmitted disease antigens, and measles, mumps and rubella antigens, growth hormones, somatotropin, blood clotting factors VIII and XIII. In addition, there may be a demand for severe acute respiratory syndrome–coronavirus antigens, hepatitis A, B and C viral‐selected antigens, HIV retroviral antigens, influenza antigens, trypanosomal antigens, and foot and mouth disease antigens. Prevention of oxidative stress has been achieved by application of antioxidant redox metalloenzymes such as superoxide dismutases (containing Cu/Zn cytosolic, Mn mitochondrial and Fe bacterial) glutathione peroxidases (and other Se‐containing proteins and enzymes such as the thioredoxins), catalases (Fe‐containing), cytochrome c peroxidases (Fe‐containing), ceruloplasmins (Cu‐containing), metallothionines (these cysteine thiol‐rich proteins bind ions of cadmium and mercury) and tyrosinases(Cu‐containing). Methods and Results: ROS are generated inadvertently by single metal valency couples such as FeII/FeIII and by FeIII/FeV present in 2700 (including 57 human) isoforms in cytochromes P450 mixed‐function oxidases (EC 1·14·14·1; O(2) : mono‐oxygenase NADPH/NADH requiring). In addition, mixed‐metal couples such as valency unmatched forms in CuI/FeII and FeIII/MnIV can recycle electrons. Moreover, proteins/protein chaperone couples can recycle electrons, often where futile‐recycling systems have been instigated. Furthermore, oxidized membrane phospholipids (R) can form ROOH (lipid hydroperoxides) and ROH (lipid alkoxides) that can generate ROS through Fenton chemistry (iron‐catalysed) chain reactions. Utilization of chain‐breaking antioxidants such as vitamin E (α‐tocopherol) in the lipid phase and vitamin C (ascorbate) in the aqueous phase can terminate these ROS‐producing reactions. Conclusions: The main significance of the study is that proteomic strategies of relief from bioprocess perturbation by ROS of yeast fermentations (used to manufacture proteins required in the food and therapeutic bioindustries) may become possible through addition of selected proteins (including metalloenzymes). The main impact of the study is that the utilization of genetically modified (GM) yeast produced by recombinant DNA technology genomic strategies could circumvent the bioprocessing problems that otherwise result from the bioprocess perturbations: this is as a result of oxidative stress caused by ROS, which is avoidable by deployment of appropriate antioxidants such as vitamins E, C and D (and antioxidant proteins and enzymes often of microbial origin via recombinant DNA technology).


id: cord-278846-nqj7ctk3
title: Macrophage metabolic reprogramming during chronic lung disease
author: Ogger, Patricia P.
date: 2020-11-12
txt: ./txt/cord-278846-nqj7ctk3.txt
cache: ./cache/cord-278846-nqj7ctk3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33184475/
doi: 10.1038/s41385-020-00356-5
summary:
  While these initial observations were made during steady state or using in vitro polarised macrophages, recent studies have indicated that during many chronic lung diseases (CLDs), AMs adapt their metabolic profile to fit their local niche. By generating reactive oxygen species (ROS) for pathogen defence, utilising aerobic glycolysis to rapidly generate cytokines, and employing mitochondrial respiration to fuel inflammatory responses, AMs utilise metabolic reprogramming for host defence, although these changes may also support chronic pathology. Indeed, many recent studies have indicated that in chronic lung diseases (CLDs), such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and during infection such as with Mycobacterium Tuberculosis (Mtb), there are significant alterations in AM metabolic processes and that targeting these pathways could represent an exciting therapeutic approach 6, 7 . Iron metabolism is therefore likely a key pathway in IPF-AMs and targeting it would be a viable option to decrease ROS, oxidative stress and macrophage activation.

abstract:
  Airway macrophages (AMs) play key roles in the maintenance of lung immune tolerance. Tissue tailored, highly specialised and strategically positioned, AMs are critical sentinels of lung homoeostasis. In the last decade, there has been a revolution in our understanding of how metabolism underlies key macrophage functions. While these initial observations were made during steady state or using in vitro polarised macrophages, recent studies have indicated that during many chronic lung diseases (CLDs), AMs adapt their metabolic profile to fit their local niche. By generating reactive oxygen species (ROS) for pathogen defence, utilising aerobic glycolysis to rapidly generate cytokines, and employing mitochondrial respiration to fuel inflammatory responses, AMs utilise metabolic reprogramming for host defence, although these changes may also support chronic pathology. ﻿This review focuses on how metabolic alterations underlie AM phenotype and function during CLDs. Particular emphasis is given to how our new understanding of AM metabolic plasticity may be exploited to develop AM-focused therapies.


id: cord-288238-36hiiw91
title: Metabolic host response and therapeutic approaches to influenza infection
author: Keshavarz, Mohsen
date: 2020-03-05
txt: ./txt/cord-288238-36hiiw91.txt
cache: ./cache/cord-288238-36hiiw91.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32161622/
doi: 10.1186/s11658-020-00211-2
summary:
  It is also reported that influenza infection significantly increases ROS production by inducing Nox4, and the proliferation of this virus in lung epithelial cells is dependent on redox-sensitive pathways activated by Nox4-derived ROS [16] . IFN can also exert its function on metabolic changes by producing several mediators including indoleamine-2,3-dioxygenase (IDO) and nitric oxide (NO), both of which appear to have either an inducible or an inhibitory role in viral replication [33] . In addition, increased temperature of cells during infection (which could be the result of virus replication and fever) causes heat stress which in turn can considerably downregulate carnitine palmitoyltransferase II (CPT II) activity and reduce the β-oxidation and ATP levels in fibroblasts of influenza-associated encephalopathy patients and healthy volunteers [110] . Through enhancing the activity of the mTORC1 complex, the influenza virus strengthens several metabolic pathways, including glycolysis, glutaminolysis, pentose phosphate, and fatty acid synthesis, to provide more ATP and structural materials for viral replication.

abstract:
  Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid β-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.


id: cord-289034-yl3emjef
title: Mitochondria at the Crossroads of Physiology and Pathology
author: Moro, Loredana
date: 2020-06-24
txt: ./txt/cord-289034-yl3emjef.txt
cache: ./cache/cord-289034-yl3emjef.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/jcm9061971
doi: 10.3390/jcm9061971
summary:
  Two mitochondria quality control mechanisms are in place to meet the functional needs of any given cell under different physiological and pathological conditions: (a) mitochondrial biogenesis, fusion and fission [4] [5] [6] ; (b) mitophagy [7, 8] . The second mechanism, mitophagy, is a specific form of autophagy that removes damaged mitochondria and reduces the mitochondrial mass upon microenvironmental stresses, such as hypoxia and nutrient starvation, promoting cell survival [11] . In this context, mutations in three TCA cycle enzymes, namely succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase, have been shown to play a causal role in carcinogenesis [54, 55] , thus providing compelling evidence for the involvement of mitochondrial metabolic alterations as cancer drivers. Mitochondrial dysfunction is implicated in several pathological conditions, ranging from neurodegenerative and cardiovascular diseases, to aging, cancer and inflammation.

abstract:
  Mitochondria play a crucial role in cell life and death by regulating bioenergetic and biosynthetic pathways. They are able to adapt rapidly to different microenvironmental stressors by accommodating the metabolic and biosynthetic needs of the cell. Mounting evidence places mitochondrial dysfunction at the core of several diseases, notably in the context of pathologies of the cardiovascular and central nervous system. In addition, mutations in some mitochondrial proteins are bona fide cancer drivers. Better understanding of the functions of these multifaceted organelles and their components may finetune our knowledge on the molecular bases of certain diseases and suggest new therapeutic avenues.


id: cord-291190-f6km3c7z
author: Nasi, Aikaterini
date: 2020-06-18
txt: ./txt/cord-291190-f6km3c7z.txt
cache: ./cache/cord-291190-f6km3c7z.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S221475002030336X?v=s5
doi: 10.1016/j.toxrep.2020.06.003
summary:
   SARS-CoV has been reported to modulate PARP function and thereby NAD+ biosynthesis  Cellular homeostasis and redox imbalances by SARS-CoV2 can cause stress responses  Antioxidants such as NAC could limit ROS mediated tissue damage during COVID-19 Hereby, based on literature review from the current pandemic and previous outbreaks with corona viruses we analyze the impact of the virus infection on cell stress responses and redox balance. PLA2G2D expression was shown to be increased in the lungs of middle aged mice, resulting in decreased survival and impaired T cell responses upon infection with SARS-CoV1 [20] . Interestingly, NAC administration to aged mice, diminished PLAG2D expression in both lung cells and CD11c+ DCs. In addition, increased levels of oxidized phospholipidsare a common feature associated with acute respiratory distress syndrome (ARDS) caused by viruses including SARS and H5N1.

title:
  Reactive oxygen species as an initiator of toxic innate immune responses in retort to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention

abstract:
  During the current COVID-19 pandemic, a need for evaluation of already available drugs for treatment of the disease is crucial. Hereby, based on literature review from the current pandemic and previous outbreaks with corona viruses we analyze the impact of the virus infection on cell stress responses and redox balance. High levels of mortality are noticed in elderly individuals infected with SARS-CoV2 and during the previous SARS-CoV1 outbreak. Elderly individuals maintain a chronic low level of inflammation which is associated with oxidative stress and inflammatory cytokine production, a condition that increases the severity of viral infections in this population. SARS-CoV2 infection can lead to alterations of redox balance in infected cells through modulation of NAD + biosynthesis, PARP function along with altering proteasome and mitochondrial function in the cell thereby leading to enhanced cell stress responses which further exacerbate inflammation. ROS production can increase IL-6 production and lipid peroxidation resulting in cell damage. Therefore, early treatment with anti-oxidants such as NAC during COVID-19 can be a way to bypass the excessive inflammation and cell damage that lead to severe infection.


id: cord-291559-h6czy5bh
title: Recent advances in pharmacological research on Ecklonia species: a review
author: Koirala, Prashamsa
date: 2017-08-24
txt: ./txt/cord-291559-h6czy5bh.txt
cache: ./cache/cord-291559-h6czy5bh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12272-017-0948-4
doi: 10.1007/s12272-017-0948-4
summary:
  A study investigated the protective effect of ES in alcoholic fatty liver and found that ES treatment suppressed adipogenesis and increased the expression of fatty acid oxidation-related genes, e.g., peroxisome proliferator-activated receptor (PPAR)-a and CPT-1, but decreased the expression of sterol regulatory element-binding protein (SREBP)-1, a triglyceride (TG) synthesis-related gene, suggesting that ES extract could be useful in preventing fatty acid oxidation and reducing lipogenesis in ethanol-induced fatty liver (Bang et al. Fucoidan extracted from EC exhibited prominent effects on peroxyl radical scavenging activity and 2, 2 0 -azobisdihydrochloride-induced oxidative stress in Vero cells and reduced ROS generation, lipid peroxidation, and cell death in a zebrafish model, proving its antioxidant capacities in vitro and in vivo despite being neither a polyphenol nor a flavonoid. Dieckol, isolated from the edible brown algae Ecklonia cava, induces apoptosis of ovarian cancer cells and inhibits tumor xenograft growth

abstract:
  The genus Ecklonia (Lessoniaceae, Phaeophyceae), commonly called kelp (brown algae), is abundant on the coasts of Japan and Korea. During the past few decades, Ecklonia species have received tremendous attention for their wide range of therapeutic properties and multiple health benefits, such as great nutritional value and being rich in vitamins, minerals, dietary fiber, proteins, and polysaccharides. Several novel functional ingredients with diversified biological activities have been isolated and possess antimicrobial, antiviral, hepatoprotective, cardioprotective, anti-inflammatory, neuroprotective, anticarcinogenic, immunomodulatory, hypolipidemic, anti-diabetic, and antioxidant therapeutic properties. The present review discusses the phytochemical, pharmacological, therapeutic, nutritional, and health benefits of different species of genus Ecklonia, as well as their use in the prevention of disease and maintenance of good health.


id: cord-293319-oo0w6faj
author: Seo, Youngsik
date: 2020-06-11
txt: ./txt/cord-293319-oo0w6faj.txt
cache: ./cache/cord-293319-oo0w6faj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s40543-020-00220-y
doi: 10.1186/s40543-020-00220-y
summary:
  The antibacterial activities against Escherichia coli, Listeria innocua, and Pseudomonas syringae DC3000 in both the absence and presence of Ag(3)PO(4) under dark conditions and in the presence of Ag(3)PO(4) under red-light (625 nm) and blue-light (460 nm) irradiation were examined. The photoinduced enhancement of the Ag(3)PO(4) antibacterial activity under blue-light irradiation is explained by the formation of ROS during the antibacterial action of the Ag(3)PO(4). Moreover, the antiviral activity of Ag(3)PO(4) against amphotropic 10A1 murine leukemia virus enhanced under blue-light irradiation via ROS production. coli in the absence and presence of Ag 3 PO 4 under dark conditions and in the presence of Ag 3 PO 4 under red-light (625 nm) and blue-light (460 nm) irradiation. These data indicate that the antibacterial activity of Ag 3 PO 4 under blue-light irradiation corresponds to the amount of ROS in E. The photoinduced enhancement of the antibacterial and antiviral activities of Ag 3 PO 4 under blue-light irradiation was observed.

title:
  Reactive-oxygen-species-mediated mechanism for photoinduced antibacterial and antiviral activities of Ag(3)PO(4)

abstract:
  Cubic-shaped Ag(3)PO(4) crystals with a mean size of 1 μm were synthesized by a precipitation method from a mixed solution of AgNO(3), Na(2)HPO(4), and triethanolamine. The antibacterial activities against Escherichia coli, Listeria innocua, and Pseudomonas syringae DC3000 in both the absence and presence of Ag(3)PO(4) under dark conditions and in the presence of Ag(3)PO(4) under red-light (625 nm) and blue-light (460 nm) irradiation were examined. The concentrations of reactive oxygen species (ROS) were also measured in the antibacterial action of the Ag(3)PO(4) against Escherichia coli. The photoinduced enhancement of the Ag(3)PO(4) antibacterial activity under blue-light irradiation is explained by the formation of ROS during the antibacterial action of the Ag(3)PO(4). Moreover, the antiviral activity of Ag(3)PO(4) against amphotropic 10A1 murine leukemia virus enhanced under blue-light irradiation via ROS production. These results provide an insight into extended bio-applications of Ag(3)PO(4).


id: cord-295459-ffi1043k
author: Khan, Naseem Ahmed
date: 2020-05-27
txt: ./txt/cord-295459-ffi1043k.txt
cache: ./cache/cord-295459-ffi1043k.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1128/msphere.00447-20
doi: 10.1128/msphere.00447-20
summary:
  Small interfering RNA (siRNA)-mediated knockdown of the ubiquitous zinc uptake transporter ZIP1 suggests that labile zinc levels are increased due to the increased uptake by RSV-infected cells as an antiviral response. Our results suggest that zinc homeostasis plays a critical role in the host response to RSV infection by regulating oxidative stress and inhibiting virus replication. As with A549 cells, we observed a time-dependent increase in labile zinc levels in SAECs infected with RSV without any effect on cell viability ( Fig. 2A and B) . To further confirm the role of oxidative stress in RSV infection, cells infected with RSV were treated with 300 M H 2 O 2 (one of the ROS) and virus titers were measured at 24 h p.i. As observed in the case of zinc chelation, addition of H 2 O 2 led to a modest but significant increase in RSV titers at 24 h p.i.

title:
  Respiratory Syncytial Virus-Induced Oxidative Stress Leads to an Increase in Labile Zinc Pools in Lung Epithelial Cells

abstract:
  Zinc supplementation in cell culture has been shown to inhibit various viruses, like herpes simplex virus, rotavirus, severe acute respiratory syndrome (SARS) coronavirus, rhinovirus, and respiratory syncytial virus (RSV). However, whether zinc plays a direct antiviral role in viral infections and whether viruses have adopted strategies to modulate zinc homeostasis have not been investigated. Results from clinical trials of zinc supplementation in infections indicate that zinc supplementation may be beneficial in a pathogen- or disease-specific manner, further underscoring the importance of understanding the interaction between zinc homeostasis and virus infections at the molecular level. We investigated the effect of RSV infection on zinc homeostasis and show that RSV infection in lung epithelial cells leads to modulation of zinc homeostasis. The intracellular labile zinc pool increases upon RSV infection in a multiplicity of infection (MOI)-dependent fashion. Small interfering RNA (siRNA)-mediated knockdown of the ubiquitous zinc uptake transporter ZIP1 suggests that labile zinc levels are increased due to the increased uptake by RSV-infected cells as an antiviral response. Adding zinc to culture medium after RSV infection led to significant inhibition of RSV titers, whereas depletion of zinc by a zinc chelator, N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) led to an increase in RSV titers. The inhibitory effect of zinc was specific, as other divalent cations had no effect on RSV titers. Both RSV infection and zinc chelation by TPEN led to reactive oxygen species (ROS) induction, whereas addition of zinc blocked ROS induction. These results suggest a molecular link between RSV infection, zinc homeostasis, and oxidative-stress pathways and provide new insights for developing strategies to counter RSV infection. IMPORTANCE Zinc deficiency rates in developing countries range from 20 to 30%, and zinc supplementation trials have been shown to correct clinical manifestations attributed to zinc deficiency, but the outcomes in the case of respiratory infections have been inconsistent. We aimed at understanding the role of zinc homeostasis in respiratory syncytial virus (RSV) infection. Infection of lung epithelial cell lines or primary small-airway epithelial cells led to an increase in labile zinc pools, which was due to increased uptake of zinc. Zinc supplementation inhibited RSV replication, whereas zinc chelation had an opposing effect, leading to increases in RSV titers. Increases in labile zinc in RSV-infected cells coincided with induction of reactive oxygen species (ROS). Both zinc depletion and addition of exogenous ROS led to enhanced RSV infection, whereas addition of the antioxidant inhibited RSV, suggesting that zinc is part of an interplay between RSV-induced oxidative stress and the host response to maintain redox balance.


id: cord-297469-26d8o1xk
author: Choi, Won Hyung
date: 2019-05-09
txt: ./txt/cord-297469-26d8o1xk.txt
cache: ./cache/cord-297469-26d8o1xk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31075881/
doi: 10.3390/pathogens8020061
summary:
  gondii effects of ursolic acid, and analyzed the production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines through co-cultured immune cells, as well as the expression of intracellular organelles of T. Furthermore, ursolic acid effectively increased the production of NO, ROS, interleukin (IL)-10, IL-12, granulocyte macrophage colony stimulating factor (GM-CSF), and interferon-β, while reducing the expression of IL-1β, IL-6, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) in T. gondii-infected cells were treated with different concentrations (12.5-200 µg/mL) of ursolic acid (UA) and sulfadiazine (SF) at 37 • C for 24 h, respectively; their survival rates were inhibited a dose-dependent manner. We evaluated the effect of ROS and NO production induced by ursolic acid in immune cells infected with T. We evaluated the effect of ROS and NO production induced by ursolic acid in immune cells infected with T.

title:
  The Mechanism of Action of Ursolic Acid as a Potential Anti-Toxoplasmosis Agent, and Its Immunomodulatory Effects

abstract:
  This study was performed to investigate the mechanism of action of ursolic acid in terms of anti-Toxoplasma gondii effects, including immunomodulatory effects. We evaluated the anti-T. gondii effects of ursolic acid, and analyzed the production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines through co-cultured immune cells, as well as the expression of intracellular organelles of T. gondii. The subcellular organelles and granules of T. gondii, particularly rhoptry protein 18, microneme protein 8, and inner membrane complex sub-compartment protein 3, were markedly decreased when T. gondii was treated with ursolic acid, and their expressions were effectively inhibited. Furthermore, ursolic acid effectively increased the production of NO, ROS, interleukin (IL)-10, IL-12, granulocyte macrophage colony stimulating factor (GM-CSF), and interferon-β, while reducing the expression of IL-1β, IL-6, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) in T. gondii-infected immune cells. These results demonstrate that ursolic acid not only causes anti-T. gondii activity/action by effectively inhibiting the survival of T. gondii and the subcellular organelles of T. gondii, but also induces specific immunomodulatory effects in T. gondii-infected immune cells. Therefore, this study indicates that ursolic acid can be effectively utilized as a potential candidate agent for developing novel anti-toxoplasmosis drugs, and has immunomodulatory activity.


id: cord-298265-elbnzgx6
title: A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics
author: Mutua, Victoria
date: 2020-08-01
txt: ./txt/cord-298265-elbnzgx6.txt
cache: ./cache/cord-298265-elbnzgx6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12016-020-08804-7
doi: 10.1007/s12016-020-08804-7
summary:
  Studies have demonstrated that circulating neutrophils of RA patients are more easily stimulated to NETosis than those from healthy subjects [73, 74] , and as in other autoimmune conditions, NETs act as a source of extracellular autoantigens leading to excessive innate and adaptive immune responses in the joints and subsequent tissue injury [73, 75] . Inhibits ROS production, prevents thrombus formation [190] [191] [192] [193] [194] [195] Nucleases Recombinant human DNase DNA matrixes Reduces neutrophil infiltration, cleaves DNA matrixes [196] [197] [198] [199] [200] [201] [202] [203] [204] [205] [206] [207] Staphylokinase Plasminogen, alpha-defensins Converting NETs to deoxyadenosine mediating death of immune cells [208] [209] [210] [211] Notable compounds Probiotics PKC pathway run a study to evaluate the effect of inhibition of PAD4 in NETosis using an antagomiR-155, a pleiotropic microRNA important in the regulation of immune responses, demonstrating a decreased induction of PAD4 mRNA and subsequent reduced NETs in response to PMA challenge [13] .

abstract:
  Activated neutrophils release neutrophil extracellular traps (NETs) in response to a variety of stimuli. NETosis is driven by protein-arginine deiminase type 4, with the release of intracellular granule components that function by capturing and destroying microbes, including viral, fungal, bacterial, and protozoal pathogens. The positive effects of pathogen control are countered by pro-inflammatory effects as demonstrated in a variety of diseases. Components of NETS are non-specific, and other than controlling microbes, they cause injury to surrounding tissue by themselves or by increasing the pro-inflammatory response. NETs can play a role in enhancement of the inflammation seen in autoimmune diseases including psoriasis, rheumatoid arthritis, and systemic lupus erythematosis. In addition, autoinflammatory diseases such as gout have been associated with NETosis. Inhibition of NETs may decrease the severity of many diseases improving survival. Herein, we describe NETosis in different diseases focusing on the detrimental effect of NETs and outline possible therapeutics that can be used to mitigate netosis. There is a need for more studies and clinical trials on these and other compounds that could prevent or destroy NETs, thereby decreasing damage to patients.


id: cord-307148-k1uo3fxm
title: COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm
author: Bradshaw, Patrick C.
date: 2020-09-09
txt: ./txt/cord-307148-k1uo3fxm.txt
cache: ./cache/cord-307148-k1uo3fxm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33014275/
doi: 10.1155/2020/6401341
summary:
  R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. Others have also suggested that increasing systemic ketone levels may aid host defenses against respiratory viral infection, in part, by decreasing inflammation [1, 2] , including a recent comprehensive review [3] , while a clinical trial of the effects of a ketogenic diet on intubated SARS-CoV-2 patients has recently been registered (NCT04358835). Coronaviruses have been shown to increase the oxidation of phospholipids, which stimulate toll-like receptor 4 (TLR4) signaling on macrophages, leading to cytokine production and acute lung injury [163] , so HDAC inhibition with R-BHB appears to be a viable treatment to decrease cytokine levels and inflammation.

abstract:
  Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.


id: cord-310723-ogo9mvi5
title: The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin
author: Belinskaia, Daria A.
date: 2020-10-09
txt: ./txt/cord-310723-ogo9mvi5.txt
cache: ./cache/cord-310723-ogo9mvi5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/antiox9100966
doi: 10.3390/antiox9100966
summary:
  Therefore, the correct extrapolation of in vivo results obtained in rats to a human organism requires the identification of amino acids involved in protein-ligand interaction, determination of all structural and conformational features of the binding sites and comparison of the obtained characteristics in HSA vs. Therefore, the correct extrapolation of in vivo results obtained in rats to a human organism requires the identification of amino acids involved in protein-ligand interaction, determination of all structural and conformational features of the binding sites and comparison of the obtained characteristics in HSA vs. It was demonstrated by the method of electron paramagnetic resonance (EPR) that oxidation of albumin of the healthy subjects with hydrogen peroxide and tert-butyl hydroperoxide led to conformational changes in the microenvironment of the binding sites of maleimide and iodoacetamide spin labels, which interact predominantly with the thiol group of Cys34.

abstract:
  As a carrier of many biologically active compounds, blood is exposed to oxidants to a greater extent than the intracellular environment. Serum albumin plays a key role in antioxidant defence under both normal and oxidative stress conditions. This review evaluates data published in the literature and from our own research on the mechanisms of the enzymatic and non-enzymatic activities of albumin that determine its participation in redox modulation of plasma and intercellular fluid. For the first time, the results of numerous clinical, biochemical, spectroscopic and computational experiments devoted to the study of allosteric modulation of the functional properties of the protein associated with its participation in antioxidant defence are analysed. It has been concluded that it is fundamentally possible to regulate the antioxidant properties of albumin with various ligands, and the binding and/or enzymatic features of the protein by changing its redox status. The perspectives for using the antioxidant properties of albumin in practice are discussed.


id: cord-313825-bbjxd86y
author: Xia, Tian
date: 2016-10-08
txt: ./txt/cord-313825-bbjxd86y.txt
cache: ./cache/cord-313825-bbjxd86y.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/nsr/nww064
doi: 10.1093/nsr/nww064
summary:
  The lung is the first target organ for air pollution and PM exposure is associated with reduced lung function, increased lung inflammation, asthma, respiratory infections, lung cancer and exacerbation of COPD, which lead to systemic inflammation and oxidative stress affecting blood, vasculature, heart and brain, ultimately contribute to the premature mortality ( Fig. 2) [3, 8, 14, 16] . These specific features of UFPs can significantly contribute to the adverse effects through ROS over-production by the redox-active organic chemicals and metals on particle surface, resulting in cellular oxidative stress [18, 19, 21, 44, 48] . These include: (i) carbon core of PM and UFPs could induce ROS generation and oxidative stress; (ii) catalytic conversion of PAHs to quinones by cytochrome P450 in the endoplasmic reticulum; (iii) quinone redox cycling by NADPH-dependent P450 reductase in microsomes; (iv) mitochondrial perturbation leading to electron leakage in the inner membrane; and (v) NADPH oxidase activity in the macrophage surface membrane and associated phagosomes.

title:
  Pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century

abstract:
  Air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. Among different air pollutants, particulate matter (PM), particularly combustion-produced fine PM (PM(2.5)) has been shown to play a major role in inducing various adverse health effects. Strong associations have been demonstrated by epidemiological and toxicological studies between increases in PM(2.5) concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. The mechanisms of PM-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. Particles in the ultrafine range (<100 nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. Yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with PM(2.5). In addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. All these add to the complexity of PM-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future.


id: cord-313918-uv9xdp5f
title: Mitochondrial Glutathione: Recent Insights and Role in Disease
author: Marí, Montserrat
date: 2020-09-24
txt: ./txt/cord-313918-uv9xdp5f.txt
cache: ./cache/cord-313918-uv9xdp5f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32987701/
doi: 10.3390/antiox9100909
summary:
  Abbreviations 2-oxoglutarate carrier (OGC; SLC25A11); adenine nucleotide translocator (ANT); alcoholic liver disease (ALD); alcoholic steatohepatitis (ASH); Alzheimer''s disease (AD); amyloid beta peptides (Aβ); amyloid precursor protein/presenilin 1 (APP/PS1); amyotrophic lateral sclerosis (ALS); Cu/Zn-superoxide dismutase (SOD1); diabetic nephropathy (DN); electron transport chain (ETC); endoplasmic reticulum (ER); free cholesterol (FC); glyoxalase II (GLO2); Glutathione (GSH); glutathione disulfide (GSSG); glutathione reductase (GR); glutathione S-transferase (GST); GSH ethyl ester (GEE); GSH peroxidases (GPx); hepatic steatosis (HS); metabolic associated fatty liver disease (MAFLD); mitochondrial dicarboxylate carrier (DIC; SLC25A10); mitochondrial glutathione (mGSH); mitochondrial NADP+-dependent isocitrate dehydrogenase (IDPm); mitochondrial permeability transition (MPT); non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); Parkinson''s disease (PD); peroxiredoxins (Prx); protein disulfide isomerase (PDI); reactive oxygen species (ROS); S-adenosyl-l-methionine (SAM); S-d-lactoylglutathione (SLG); sterol regulatory element binding protein 2 (SREBP-2); thioredoxin 2/thioredoxin reductase 2 (Trx2/TrxR2); tumor necrosis factor (TNF).

abstract:
  Mitochondria are the main source of reactive oxygen species (ROS), most of them deriving from the mitochondrial respiratory chain. Among the numerous enzymatic and non-enzymatic antioxidant systems present in mitochondria, mitochondrial glutathione (mGSH) emerges as the main line of defense for maintaining the appropriate mitochondrial redox environment. mGSH’s ability to act directly or as a co-factor in reactions catalyzed by other mitochondrial enzymes makes its presence essential to avoid or to repair oxidative modifications that can lead to mitochondrial dysfunction and subsequently to cell death. Since mitochondrial redox disorders play a central part in many diseases, harboring optimal levels of mGSH is vitally important. In this review, we will highlight the participation of mGSH as a contributor to disease progression in pathologies as diverse as Alzheimer’s disease, alcoholic and non-alcoholic steatohepatitis, or diabetic nephropathy. Furthermore, the involvement of mitochondrial ROS in the signaling of new prescribed drugs and in other pathologies (or in other unmet medical needs, such as gender differences or coronavirus disease of 2019 (COVID-19) treatment) is still being revealed; guaranteeing that research on mGSH will be an interesting topic for years to come.


id: cord-316244-s5ua0re3
title: Roles of peroxiredoxins in cancer, neurodegenerative diseases and inflammatory diseases
author: Park, Mi Hee
date: 2016-04-26
txt: ./txt/cord-316244-s5ua0re3.txt
cache: ./cache/cord-316244-s5ua0re3.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0163725816300407
doi: 10.1016/j.pharmthera.2016.03.018
summary:
  PRDX6 is an oxidative stress inducible protein regulated by Nrf2 and activation of the gene expression was observed in mouse lungs by hyperoxia and in cultured lung epithelial cells following treatment with H 2 O 2 or paraquat . One previous study reported that hypoxia increases AR activity in prostate cancer cells, and that PRDX1, which is upregulated by hypoxia, interacts with AR to enhance the expression of androgen-regulated genes (Chhipa, Lee, Onate, Wu, & Ip, 2009; Park et al., 2006) . PRDX2 is overexpressed in colorectal carcinoma tissues compared with the matched non-cancer colorectal mucosa tissues and that expression is positively associated with tumor metastasis and the TNM stage by regulation of oxidation induced apoptosis (Lu et al., 2014a) . Other researchers also demonstrated that PRDX2 knockdown using a lentiviral vector-mediated specific shRNA inhibited cell growth, stimulated apoptosis, and augmented the production of endogenous ROS that led to an altered expression of proteins associated with the Wnt signaling pathway (Lu et al., 2014b) .

abstract:
  Peroxiredoxins (PRDXs) are antioxidant enzymes, known to catalyze peroxide reduction to balance cellular hydrogen peroxide (H(2)O(2)) levels, which are essential for cell signaling and metabolism and act as a regulator of redox signaling. Redox signaling is a critical component of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Early studies demonstrated that PRDXs regulates cell growth, metabolism and immune regulation and therefore involved in the pathologic regulator or protectant of several cancers, neurodegenerative diseases and inflammatory diseases. Oxidative stress and antioxidant systems are important regulators of redox signaling regulated diseases. In addition, thiol-based redox systems through peroxiredoxins have been demonstrated to regulate several redox-dependent process related diseases. In this review article, we will discuss recent findings regarding PRDXs in the development of diseases and further discuss therapeutic approaches targeting PRDXs. Moreover, we will suggest that PRDXs could be targets of several diseases and the therapeutic agents for targeting PRDXs may have potential beneficial effects for the treatment of cancers, neurodegenerative diseases and inflammatory diseases. Future research should open new avenues for the design of novel therapeutic approaches targeting PRDXs.


id: cord-319614-4qi59pbz
author: Benej, Martin
date: 2019-10-25
txt: ./txt/cord-319614-4qi59pbz.txt
cache: ./cache/cord-319614-4qi59pbz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31708904/
doi: 10.3389/fmicb.2019.02438
summary:
  Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. Increased levels of ROS were accompanied by changes in the pattern of telomere restriction fragments (TRFs) in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. These data suggest that LCMV maintains its replication in persistently infected cells by regulating redox signaling through modulation of local levels of H 2 O 2 and subsequent activation of cellular processes that it uses for its own benefit. Notably, the treatment with antioxidants also resulted in reduced levels of viral NP in HeLa, as well as in A549 LCMV-infected cells, suggesting a link between ROS-dependent signaling and virus replication (Figures 7B,D and Supplementary Figure S2B ).

title:
  Quantitative Proteomics Reveal Peroxiredoxin Perturbation Upon Persistent Lymphocytic Choriomeningitis Virus Infection in Human Cells

abstract:
  Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. In order to shed more light on these processes, two-dimensional differential in-gel electrophoresis (2D-DIGE) and MALDI-TOF tandem mass spectrometry were used to determine the proteome response of the HeLa cell line to persistent LCMV infection. Quantitative analysis revealed 24 differentially abundant proteins. Functional analysis showed that LCMV-responsive proteins were primarily involved in metabolism, stress, and the defense response. Among identified proteins, we discovered significant changes for peroxiredoxins, a family of antioxidant enzymes. Decreased amount of these antioxidant proteins correlated with elevation of reactive oxygen species (ROS) in infected cells. Increased levels of ROS were accompanied by changes in the pattern of telomere restriction fragments (TRFs) in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Moreover, treatment with antioxidants resulted in reduced levels of viral nucleoprotein, indicating a connection between ROS-dependent signaling and viral replication.


id: cord-320591-re99v1qt
author: Le, Thanh Ninh
date: 2020-07-27
txt: ./txt/cord-320591-re99v1qt.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/32727144/
doi: 10.3390/plants9080946
summary:
  Particularly, these studies mostly focused on the antioxidant and anticancer activities of broccoli sprouts and microgreens owing to the functions of glucosinolates and phenolic compounds (Tables 4 and 5 ). Particularly, these studies mostly focused on the antioxidant and anticancer activities of broccoli sprouts and microgreens owing to the functions of glucosinolates and phenolic compounds (Tables 4 and 5 ). In summary, previous studies showed that broccoli sprout extracts rich in vitamins, carotenoids, and phenolic compounds showed very high antioxidant activity in both in vitro and in vivo tests (Table 4) . Moreover, the previous studies have focused on several biological activities of broccoli seedlings, such as antioxidant, anticancer, antimicrobial, and anti-inflammatory, as well as the potentially beneficial effects for patients with cancers, diabetes, and obesity.

title:
  Bioactive Compounds and Bioactivities of Brassica oleracea L. var. Italica Sprouts and Microgreens: An Updated Overview from a Nutraceutical Perspective

abstract:
  Sprouts and microgreens, the edible seedlings of vegetables and herbs, have received increasing attention in recent years and are considered as functional foods or superfoods owing to their valuable health-promoting properties. In particular, the seedlings of broccoli (Brassica oleracea L. var. Italica) have been highly prized for their substantial amount of bioactive constituents, including glucosinolates, phenolic compounds, vitamins, and essential minerals. These secondary metabolites are positively associated with potential health benefits. Numerous in vitro and in vivo studies demonstrated that broccoli seedlings possess various biological properties, including antioxidant, anticancer, anticancer, antimicrobial, anti-inflammatory, anti-obesity and antidiabetic activities. The present review summarizes the updated knowledge about bioactive compounds and bioactivities of these broccoli products and discusses the relevant mechanisms of action. This review will serve as a potential reference for food selections of consumers and applications in functional food and nutraceutical industries.


id: cord-323730-5iawbnua
title: Oxidative stress in multiple sclerosis: Central and peripheral mode of action
author: Ohl, Kim
date: 2016-03-31
txt: ./txt/cord-323730-5iawbnua.txt
cache: ./cache/cord-323730-5iawbnua.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26626971/
doi: 10.1016/j.expneurol.2015.11.010
summary:
  Whatever the trigger factors for lesion Experimental Neurology 277 (2016) [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] Abbreviations: APCs, antigen-presenting cells; ARE, antioxidant response element; DMF, dimethyl fumarate; FAEs, fumaric acid esters; GSH, glutathione; HO, heme oxygenase; IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; Keap1, Kelch ECH associating protein 1; MDSC, myeloid-derived suppressor cells; MMF, monomethyl fumarate; NQO1, NAD(P)H: quinone oxidoreductase 1; Nrf2, nuclear factor (erythroid-derived 2)-like 2; RNS, reactive nitrogen species; ROS, reactive oxygen species; S1P, sphingosine 1-phosphate; TGF, transforming growth factor; T h , T helper cell; T reg , regulatory T cell; Trx, thioredoxin. Furthermore, redox stress is important for the functional outcome during experimentally-induced adaptive-immunity responses; e.g. in a graft-versus-host disease mouse model, free radical scavenger therapy with NecroX-7 attenuates disease severity, probably via the induction of T reg cells (Im et al., 2015) and oxidative damage regulates antigen-specific T cell responses in agerelated macular degeneration (Cruz-Guilloty et al., 2014) .

abstract:
  Accumulating evidence suggests that oxidative stress plays a major role in the pathogenesis of multiple sclerosis (MS). Reactive oxygen species (ROS), which if produced in excess lead to oxidative stress, have been implicated as mediators of demyelination and axonal damage in both MS and its animal models. One of the most studied cell populations in the context of ROS-mediated tissue damage in MS are macrophages and their CNS companion, microglia cells. However, and this aspect is less well appreciated, the extracellular and intracellular redox milieu is integral to many processes underlying T cell activation, proliferation and apoptosis. In this review article we discuss how oxidative stress affects central as well as peripheral aspects of MS and how manipulation of ROS pathways can potentially affect the course of the disease. It is our strong belief that the well-directed shaping of ROS pathways has the potential to ameliorate disease progression in MS.


id: cord-331673-xv1tcugl
title: Hard Nanomaterials in Time of Viral Pandemics
author: Reina, Giacomo
date: 2020-07-15
txt: ./txt/cord-331673-xv1tcugl.txt
cache: ./cache/cord-331673-xv1tcugl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1021/acsnano.0c04117
doi: 10.1021/acsnano.0c04117
summary:
  For instance, in the case of Herpesviridae and Paramyxoviridae viruses (both enveloped viruses with embedded viral-encoded glycoproteins), AgNPs can effectively reduce their infectivity, by blocking the interaction between the viral particles and the host cells with an antiviral activity strictly dependent on the size and ζ potential of the AgNPs. As a general observation, it was reported that smaller nanoparticles have better antiviral effect. cAgNPs could reduce cytopathic effects induced by RSV and showed efficient antiviral activity against infection by directly inactivating the virus prior to entry into the host cells. have reported that porous AuNPs are able to inhibit influenza A infection more efficiently than nonporous AuNPs. 39 This effect has been associated with the higher surface area of the porous material that favors their interaction with capsids and thus increases their antiviral activity ( Figure 4 ).

abstract:
  [Image: see text] The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.


id: cord-335676-7ak53hto
author: Meftahi, Gholam Hossein
date: 2020-06-11
txt: ./txt/cord-335676-7ak53hto.txt
cache: ./cache/cord-335676-7ak53hto.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s00011-020-01372-8
doi: 10.1007/s00011-020-01372-8
summary:
  It seems that "cytokine storm" phenomenon in elderly patients with severe COVID-19 infection, is associated with many age-related pathophysiologic processes, including alteration of angiotensin-converting enzyme 2 (ACE2) receptor expression [9] , excess ROS production [10] , alteration of autophagy [11] , the inflammatory phenotype of senescent cell activity, particularly adipose tissue [12] , and immune-senescence [13] , as well as lack of vitamin D content [14] . As shown in Fig. 2 , several factors, including alteration of ACE2 receptor expression, excess reactive oxygen species (ROS) production, senescent adipocytes activity, alteration of autophagy and mitophagy, immune-senescent, as well as vitamin D (VD) deficiency, may associate "inflame-aging" to cytokine storm in elderly patients of COVID-19. Furthermore, the lack of VD in aged subjects is associated with the pro-inflammatory phenotype of immune cells, leading to likely increasing the risk of elderly adults with chronic mild inflammation condition [122] .

title:
  The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging”

abstract:
  PURPOSE: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by “inflamm-aging”. It is highly likely that “inflamm-aging” is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. RESULTS: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of “inflamm-aging”, mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.


id: cord-336201-fl606l3b
title: The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System
author: Daryabor, Gholamreza
date: 2020-07-22
txt: ./txt/cord-336201-fl606l3b.txt
cache: ./cache/cord-336201-fl606l3b.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32793223/
doi: 10.3389/fimmu.2020.01582
summary:
  Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. T2DM, the most common form of diabetes (∼90%), is characterized by a systemic inflammatory disease accompanied by insulin resistance (IR) or decreased metabolic response to insulin in several tissues, including the adipose tissue, liver, and skeletal muscle, as well as by reduced insulin synthesis by pancreatic beta cells (4, 5) . During the progression of diabetes, hyperglycemia promotes mitochondrial dysfunction and induces the formation of reactive oxygen species (ROS) that cause oxidative stress in several tissues such as blood vessels and pancreatic beta cells (7) (8) (9) . In addition, the attachment of AGEs to their receptors [e.g., CD36, galectin-3, scavenger receptors types I (SR-A1), and II (SR-A2)] on the surfaces of immune cells in the circulation and tissues activates the expression of pro-inflammatory cytokines and increases free radical generation (18) .

abstract:
  Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.


