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10.3389/fphar.2021.626510 http://scihub22266oqcxt.onion/10.3389/fphar.2021.626510 34276356!8284048!34276356     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Front+Pharmacol 2021 ; 12 (ä): 626510 Nephropedia Template TP {{tp|p=34276356|t=2021. Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys |pdf=|usr=}}{{34276356}} gab.com Text Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys JO: Front Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=34276356 #FOAvip Aim: Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys is currently unknown. We aimed to determine the effect of remdesivir on renal fibrosis and its downstream mechanisms. Methods: Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-beta stimulated renal fibroblasts (NRK-49F) and human renal epithelial (HK2) cells. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson's trichrome staining and Western blotting. Results: Remdesivir and GS-441524 inhibited the expression of fibrotic markers (fibronectin and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis in UUO kidneys. Renal and liver function were unchanged in remdesivir treated UUO mice. Two remdesivir metabolites were detected after injection. Phosphorylation of Smad3 that was enhanced in cell and animal models for renal fibrosis was attenuated by remdesivir. In addition, the expression of Smad7, an anti-fibrotic factor, was increased after remdesivir treatment in vitro and in vivo. Moreover, knockdown of Smad7 blocked the antifibrotic effect of GS and RDV on renal cells. Conclusion: Remdesivir inhibits renal fibrosis in obstructed kidneys. Twit Text FOAVip Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys ????Front Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=34276356 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34276356 #FOAvip English Wikipedia <ref>{{Cite pmid|34276356}}</ref> Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys #MMPMID34276356 Xu L; Tan B; Huang D; Yuan M; Li T; Wu M; Ye C Front Pharmacol 2021[]; 12 (ä): 626510 PMID34276356show ga Aim: Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys is currently unknown. We aimed to determine the effect of remdesivir on renal fibrosis and its downstream mechanisms. Methods: Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-beta stimulated renal fibroblasts (NRK-49F) and human renal epithelial (HK2) cells. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson's trichrome staining and Western blotting. Results: Remdesivir and GS-441524 inhibited the expression of fibrotic markers (fibronectin and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis in UUO kidneys. Renal and liver function were unchanged in remdesivir treated UUO mice. Two remdesivir metabolites were detected after injection. Phosphorylation of Smad3 that was enhanced in cell and animal models for renal fibrosis was attenuated by remdesivir. In addition, the expression of Smad7, an anti-fibrotic factor, was increased after remdesivir treatment in vitro and in vivo. Moreover, knockdown of Smad7 blocked the antifibrotic effect of GS and RDV on renal cells. Conclusion: Remdesivir inhibits renal fibrosis in obstructed kidneys. äRemdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys (epmc).pdf DeepDyve Pubget Overpricing