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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 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 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\28507324 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Sci+Rep 2017 ; 7 (1 ): 1884 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[May]; 7 (1 ): 1884 PMID28507324 show 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. |Animals [MESH] |Cell Line [MESH] |Disease Models, Animal [MESH] |Extracellular Matrix/metabolism [MESH] |Fibrosis [MESH] |Hepatitis/drug therapy/etiology/metabolism/pathology [MESH] |Histones/metabolism [MESH] |Humans [MESH] |I-kappa B Kinase/metabolism [MESH] |Indoles/*pharmacology [MESH] |Kidney Diseases/drug therapy/etiology/*metabolism/*pathology [MESH] |Lipopolysaccharides/adverse effects [MESH] |Male [MESH] |Methylation [MESH] |Mice [MESH] |Models, Biological [MESH] |Phosphorylation/drug effects [MESH] |Signal Transduction/*drug effects [MESH] |Smad3 Protein/metabolism [MESH] |Transforming Growth Factor beta1/*metabolism [MESH]A novel indole compound MA-35 attenuates renal fibrosis by inhibiting (epmc).pdf DeepDyve Pubget Overpricing