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10.1172/jci.insight.145027 http://scihub22266oqcxt.onion/10.1172/jci.insight.145027 33284134!7934846!33284134     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\33284134.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       JCI+Insight 2021 ; 6 (2): ä Nephropedia Template TP {{tp|p=33284134|t=2021. Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity |pdf=|usr=}}{{33284134}} gab.com Text Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity JO: JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=33284134 #FOAvip Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2-induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2-induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19. Twit Text FOAVip Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity ????JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=33284134 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33284134 #FOAvip English Wikipedia <ref>{{Cite pmid|33284134}}</ref> Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity #MMPMID33284134 Li S; Ma F; Yokota T; Garcia G Jr; Palermo A; Wang Y; Farrell C; Wang YC; Wu R; Zhou Z; Pan C; Morselli M; Teitell MA; Ryazantsev S; Fishbein GA; Hoeve JT; Arboleda VA; Bloom J; Dillon B; Pellegrini M; Lusis AJ; Graeber TG; Arumugaswami V; Deb A JCI Insight 2021[Jan]; 6 (2): ä PMID33284134show ga Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2-induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2-induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19. |Angiotensin-Converting Enzyme 2/genetics/metabolism[MESH] |Animals[MESH] |Animals, Genetically Modified[MESH] |COVID-19/*complications/metabolism/physiopathology/virology[MESH] |Citric Acid Cycle/physiology[MESH] |DNA Methylation/physiology[MESH] |Disease Models, Animal[MESH] |Epigenesis, Genetic/*immunology[MESH] |Failure to Thrive/*etiology/physiopathology[MESH] |Humans[MESH] |Immunity/genetics[MESH] |Male[MESH] |Mice[MESH] |Oxidative Phosphorylation[MESH] |Renin-Angiotensin System/physiology[MESH] |SARS-CoV-2/metabolism/*pathogenicity[MESH]Metabolic reprogramming and epigenetic changes of vital organs in SAR(epmc).pdf DeepDyve Pubget Overpricing