To the Editor:Sarcopenia is defined as age-related loss of skeletal musclemass and strength,with an incidence of5%to 13%in persons aged>60 years.[1]Sarcopenia is considered a major contributor of frailty in the eld...To the Editor:Sarcopenia is defined as age-related loss of skeletal musclemass and strength,with an incidence of5%to 13%in persons aged>60 years.[1]Sarcopenia is considered a major contributor of frailty in the elderly,and frailty is reported to be associated withpoor outcomes of older people.Sarcopenia can also increase the risk of falls and fractures.展开更多
Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary stricture.Mesenchymal stem cells(MSCs)are used to treat liver diseases because of their immune regul...Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary stricture.Mesenchymal stem cells(MSCs)are used to treat liver diseases because of their immune regulation and regeneration-promoting functions.This study was performed to explore the therapeutic potential of human placental MSCs(hP-MSCs)in PSC through the Takeda G protein-coupled receptor 5(TGR5)receptor pathway.Liver tissues were collected from patients with PSC and healthy donors(n=4)for RNA sequencing and intrahepatic cholangiocyte organoid construction.hP-MSCs were injected via the tail vein into Mdr2^(-/-),bile duct ligation(BDL),and 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary cholangitis.Changes in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry(LC-MS/MS).Compared with healthy controls,liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis,and marked downregulation of bile acid receptor TGR5 expression.hP-MSC treatment apparently reduced the inflammation,cholestasis,and fibrosis in Mdr2^(-/-),BDL,and DDC model mice.By activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway,hP-MSC treatment promoted the proliferation of cholangiocytes,and affected the transcription of downstream nuclear factorκB through regulation of the binding of TGR5 and Pellino3,thereby affecting the cholangiocyte inflammatory phenotype.展开更多
基金supported by the National Key Research and Development Program(No.2018YFC2000301)Key Research&Development Program of Zhejiang(No.2022C03161)
文摘To the Editor:Sarcopenia is defined as age-related loss of skeletal musclemass and strength,with an incidence of5%to 13%in persons aged>60 years.[1]Sarcopenia is considered a major contributor of frailty in the elderly,and frailty is reported to be associated withpoor outcomes of older people.Sarcopenia can also increase the risk of falls and fractures.
基金supported by the National Key Research and Development Program of China(No.2020YFA0113003)the Key Research and Development Project of Zhejiang Province(No.2023C03046)+1 种基金the Fundamental Research Funds for the Central Universities(No.2022ZFJH003)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(Nos.JNL-2022026C and JNL-2023003C).
文摘Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary stricture.Mesenchymal stem cells(MSCs)are used to treat liver diseases because of their immune regulation and regeneration-promoting functions.This study was performed to explore the therapeutic potential of human placental MSCs(hP-MSCs)in PSC through the Takeda G protein-coupled receptor 5(TGR5)receptor pathway.Liver tissues were collected from patients with PSC and healthy donors(n=4)for RNA sequencing and intrahepatic cholangiocyte organoid construction.hP-MSCs were injected via the tail vein into Mdr2^(-/-),bile duct ligation(BDL),and 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary cholangitis.Changes in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry(LC-MS/MS).Compared with healthy controls,liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis,and marked downregulation of bile acid receptor TGR5 expression.hP-MSC treatment apparently reduced the inflammation,cholestasis,and fibrosis in Mdr2^(-/-),BDL,and DDC model mice.By activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway,hP-MSC treatment promoted the proliferation of cholangiocytes,and affected the transcription of downstream nuclear factorκB through regulation of the binding of TGR5 and Pellino3,thereby affecting the cholangiocyte inflammatory phenotype.
