key: cord-0054068-j3d4w22c
authors: nan
title: This Month in AJP
date: 2020-12-19
journal: Am J Pathol
DOI: 10.1016/j.ajpath.2020.12.003
sha: c3e4fe60eb563358b74442ceb83c4bb7797d94bf
doc_id: 54068
cord_uid: j3d4w22c

nan

The lack of Q2 relevant animal models has limited our understanding of coronavirus disease 2019 (COVID-19) pathobiology and testing possible interventions. Using aged African green monkeys (AGMs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Blair et al (Am J Pathol 2021, XXXXeXXXX) modeled acute respiratory distress syndrome (ARDS), which is a common symptom in severely ill COVID-19 patients, and often a cause of death. Eight aged AGMs were exposed to SARS-CoV-2, and they exhibited mild to severe COVID-19 with increased levels of plasma IL-6, a predictive biomarker and potential therapeutic target. In two AGMs, the disease progressed to ARDS, and these AGMs exhibited pathologic lesions and disease reported in severely ill COVID-19 human patients. Aged AGMs may help model severe COVID-19 to study the pathobiology and underlying mechanisms and explore treatment options.

The link between oxidative stress and inflammation in the lacrimal gland (LG) is unclear. Using mouse models, de Souza et al (Am J Pathol 2021, XXXXeXXXX) explored the role of age-related oxidative stress in LG inflammation. An age-dependent increase in the infiltration of immune cells was observed in the LG. The number of goblet cells was significantly lower in aged mice compared with young mice.

LG inflammation was increased and correlated with an increased level of oxidative stress markers. Lack of nuclear factor erythroid-derived-2erelated factor 2 (Nrf2), a regulator of antioxidant genes, increased inflammation in middle-aged Nrf2-deficient mice compared with control mice. Inflammation in LG decreased, and the number of goblet cells increased, when normal aged mice were fed Nrf2-inducing diet compared with standard diet. Oxidative stress pathways may be targeted to treat age-related dry eye.

Integrins are critical for hepatocyteeextracellular matrix (ECM) interactions. Using inducible integrin b1edeficient mice and liver cell cultures, Masuzaki et al (Am J Pathol 2021, XXXXeXXXX) studied the role of integrin b1 in liver microstructure development and restructuring after liver injury. Integrin b1 was found to be critical for microscopic patterning of the liver, bile canaliculi formation in developing liver, re-establishment of liver architecture after liver injury, and inhibition of transforming growth factor-b1 signaling from hepatocytes during liver maturation. Integrin b1 is critical in maintaining liver architecture; disrupting hepatocyte-ECM interaction may be sufficient to drive fibrosis.

The ubiquitin-conjugating enzyme RAD6B Q3 stabilizes bcatenin, and its depletion reverses epithelial-tomesenchymal transition in breast cancer cells. Using gene editing and a small-molecule inhibitor of RAD6, Sarma et al (Am J Pathol 2021, XXXXeXXXX) studied the role of RAD6B in the development and progression of melanoma. Limiting RAD6 inhibited melanoma cell proliferation. Loss or inhibition of RAD6B in metastatic melanoma cells downregulated b-catenin signaling and downstream effectors, and decreased cell migration/invasion, tumor growth, and lung metastasis. RAD6B may be targeted to treat melanoma.

The role of the GTPase R-Ras in high endothelial venule (HEV) function is unclear. Using Rras knockout (KO) mice and cell cultures, Sawada et al (Am J Pathol 2021, XXXXeXXXX) explored this role. Endothelial cellespecific inducible Rras KO mice were generated, and pathogen-induced naïve T-cell trafficking to lymph nodes was studied. On immune challenge, HEVs transiently upregulated R-Ras in mice in a tumor necrosis factoredependent manner. Vascular R-Ras is critical in regulating transendothelial migration of naïve T cells into the inflamed lymph nodes. 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60  61  62  63  64  65 

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