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10.1038/s41598-017-01702-7 http://scihub22266oqcxt.onion/10.1038/s41598-017-01702-7 C5432497!5432497!28507324     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Sci+Rep 2017 ; 7 (ä): ä Nephropedia Template TP {{tp|p=28507324|t=2017. A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-? and TGF-?1 pathways |pdf=|usr=}}{{28507324}} gab.com Text A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF- and TGF- 1 pathways JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=28507324 #FOAvip Renal fibrosis is closely related to chronic inflammation and is under the control of epigenetic regulations. Because the signaling of transforming growth factor-?1 (TGF-?1) and tumor necrosis factor-? (TNF-?) play key roles in progression of renal fibrosis, dual blockade of TGF-?1 and TNF-? is desired as its therapeutic approach. Here we screened small molecules showing anti-TNF-? activity in the compound library of indole derivatives. 11 out of 41 indole derivatives inhibited the TNF-? effect. Among them, Mitochonic Acid 35 (MA-35), 5-(3, 5-dimethoxybenzyloxy)-3-indoleacetic acid, showed the potent effect. The anti-TNF-? activity was mediated by inhibiting I?B kinase phosphorylation, which attenuated the LPS/GaIN-induced hepatic inflammation in the mice. Additionally, MA-35 concurrently showed an anti-TGF-?1 effect by inhibiting Smad3 phosphorylation, resulting in the downregulation of TGF-?1-induced fibrotic gene expression. In unilateral ureter obstructed mouse kidney, which is a renal fibrosis model, MA-35 attenuated renal inflammation and fibrosis with the downregulation of inflammatory cytokines and fibrotic gene expressions. Furthermore, MA-35 inhibited TGF-?1-induced H3K4me1 histone modification of the fibrotic gene promoter, leading to a decrease in the fibrotic gene expression. MA-35 affects multiple signaling pathways involved in the fibrosis and may recover epigenetic modification; therefore, it could possibly be a novel therapeutic drug for fibrosis. Twit Text FOAVip A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF- and TGF- 1 pathways ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=28507324 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28507324 #FOAvip English Wikipedia <ref>{{Cite pmid|28507324}}</ref> A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-? and TGF-?1 pathways #MMPMID28507324 Shima H; Sasaki K; Suzuki T; Mukawa C; Obara T; Oba Y; Matsuo A; Kobayashi T; Mishima E; Watanabe S; Akiyama Y; Kikuchi K; Matsuhashi T; Oikawa Y; Nanto F; Akiyama Y; Ho HJ; Suzuki C; Saigusa D; Masamune A; Tomioka Y; Masaki T; Ito S; Hayashi Ki; Abe T Sci Rep 2017[]; 7 (ä): ä PMID28507324show ga Renal fibrosis is closely related to chronic inflammation and is under the control of epigenetic regulations. Because the signaling of transforming growth factor-?1 (TGF-?1) and tumor necrosis factor-? (TNF-?) play key roles in progression of renal fibrosis, dual blockade of TGF-?1 and TNF-? is desired as its therapeutic approach. Here we screened small molecules showing anti-TNF-? activity in the compound library of indole derivatives. 11 out of 41 indole derivatives inhibited the TNF-? effect. Among them, Mitochonic Acid 35 (MA-35), 5-(3, 5-dimethoxybenzyloxy)-3-indoleacetic acid, showed the potent effect. The anti-TNF-? activity was mediated by inhibiting I?B kinase phosphorylation, which attenuated the LPS/GaIN-induced hepatic inflammation in the mice. Additionally, MA-35 concurrently showed an anti-TGF-?1 effect by inhibiting Smad3 phosphorylation, resulting in the downregulation of TGF-?1-induced fibrotic gene expression. In unilateral ureter obstructed mouse kidney, which is a renal fibrosis model, MA-35 attenuated renal inflammation and fibrosis with the downregulation of inflammatory cytokines and fibrotic gene expressions. Furthermore, MA-35 inhibited TGF-?1-induced H3K4me1 histone modification of the fibrotic gene promoter, leading to a decrease in the fibrotic gene expression. MA-35 affects multiple signaling pathways involved in the fibrosis and may recover epigenetic modification; therefore, it could possibly be a novel therapeutic drug for fibrosis. äA novel indole compound MA-35 attenuates renal fibrosis by inhibiting (epmc).pdf DeepDyve Pubget Overpricing