Background:Tauroursodeoxycholic acid(TUDCA),a hydrophilic bile acid,is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases.Meanwhile,TUDCA has been shown to modu...Background:Tauroursodeoxycholic acid(TUDCA),a hydrophilic bile acid,is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases.Meanwhile,TUDCA has been shown to modulate the intestinal barrier function and alleviate DSS-induced colitis in mice.However,the effect of TUDCA on the intestinal barrier of weaned piglets remains largely unclear.Methods:The weaned piglets and porcine IPEC-J2 intestinal epithelial cells were used to investigate the effects of TUDCA on intestinal barrier function in weaned piglets and explore the possible underlying mechanisms.In vivo,72 healthy weaned piglets were randomly allocated into 2 groups according to their gender and body weight,and piglets were fed the basal diet with 0(control,CON)and 200 mg/kg TUDCA for 30 d,respectively.Three female and three male piglets reflecting the average bodyweight were slaughtered in each group and samples were collected.In vitro,IPEC-J2 cells were subjected to 100μmol/L TUDCA to explore the possible underlying mechanisms.Results:Our results demonstrated that dietary TUDCA supplementation significantly reduced the diarrhea incidence of weaned piglets,possibly attributing to the TUDCA-enhanced intestinal barrier function and immunity.In addition,TUDCA supplementation altered serum metabolites and the relative abundance of certain gut bacteria,which might contribute to the improved intestinal barrier function.Furthermore,the in-vitro results showed that TUDCA improved the E.coli-induced epithelial barrier impairment of IPEC-J2 cells and increased Takeda G-coupled protein receptor 5(TGR5)protein expression.However,knockdown of TGR5 and inhibition of myosin light chain kinase(MLCK)pathway abolished the TUDCA-improved epithelial barrier impairment in E.coli-treated IPEC-J2 cells,indicating the involvement of TGR5-MLCK in this process.Conclusions:These findings showed that TUDCA improved intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets,suggesting the potential application of TUDCA in improving gut health in piglet production.展开更多
Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seaso...Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza(HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid(TUDCA), a clinically available ER stress inhibitor, both in vitro and in vivo. Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity,an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals.展开更多
Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"...Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"No pretreated and without TUDCA"of the published article.Therefore,the corrected Fig.2c should be as follows:The online version of the original artice can be found at https://doi.org/10.101/j.scib.2018.08.0131.展开更多
基金supported by the National Natural Science Foundation of China(31972636,31672508,31790411 and 31802103)the National Key Research and Development Program of China(2017YFD0500501)+1 种基金the Guangdong Key Areas Research and Development Project(2019B020218001)the Provincial Agricultural Science and Technology Innovation Promotion and Agricultural Resources and Ecological Environmental Protection Construction Project(2021KJ266).
文摘Background:Tauroursodeoxycholic acid(TUDCA),a hydrophilic bile acid,is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases.Meanwhile,TUDCA has been shown to modulate the intestinal barrier function and alleviate DSS-induced colitis in mice.However,the effect of TUDCA on the intestinal barrier of weaned piglets remains largely unclear.Methods:The weaned piglets and porcine IPEC-J2 intestinal epithelial cells were used to investigate the effects of TUDCA on intestinal barrier function in weaned piglets and explore the possible underlying mechanisms.In vivo,72 healthy weaned piglets were randomly allocated into 2 groups according to their gender and body weight,and piglets were fed the basal diet with 0(control,CON)and 200 mg/kg TUDCA for 30 d,respectively.Three female and three male piglets reflecting the average bodyweight were slaughtered in each group and samples were collected.In vitro,IPEC-J2 cells were subjected to 100μmol/L TUDCA to explore the possible underlying mechanisms.Results:Our results demonstrated that dietary TUDCA supplementation significantly reduced the diarrhea incidence of weaned piglets,possibly attributing to the TUDCA-enhanced intestinal barrier function and immunity.In addition,TUDCA supplementation altered serum metabolites and the relative abundance of certain gut bacteria,which might contribute to the improved intestinal barrier function.Furthermore,the in-vitro results showed that TUDCA improved the E.coli-induced epithelial barrier impairment of IPEC-J2 cells and increased Takeda G-coupled protein receptor 5(TGR5)protein expression.However,knockdown of TGR5 and inhibition of myosin light chain kinase(MLCK)pathway abolished the TUDCA-improved epithelial barrier impairment in E.coli-treated IPEC-J2 cells,indicating the involvement of TGR5-MLCK in this process.Conclusions:These findings showed that TUDCA improved intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets,suggesting the potential application of TUDCA in improving gut health in piglet production.
基金supported by the National Natural Science Foundation of China (81788101, 81573587 and 81490531)the Ministry of Science and Technology of China (2015CB5534/6)+3 种基金111 project (B08007)the Peking Union Medical College Youth FundFundamental Research Funds for Central Universities (3332013132)the CAMS Innovation Fund for Medical Sciences (2017-I2M-1-009)
文摘Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza(HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid(TUDCA), a clinically available ER stress inhibitor, both in vitro and in vivo. Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity,an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals.
文摘Following the published article[1].the authors noticed an error duplication of image of DAPI in Fig.2c"AF"and"No pretreated and without TUDCA".The correct DAPI image was in the merged image of"No pretreated and without TUDCA"of the published article.Therefore,the corrected Fig.2c should be as follows:The online version of the original artice can be found at https://doi.org/10.101/j.scib.2018.08.0131.
