This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(P34HB)ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem ...This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(P34HB)ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells(HUCMSCs).Utilizing dual-nozzle and cell electrospinning techniques,the system encapsulates L-ascorbic acid-2-phosphate magnesium(AsP),βB-glycerophosphate sodium and dexamethasone(DEX)within the'fbers,ensuring sustained osteogenic differentiation.The scaffold's morphology,characterization,hydrophilicity,mechanical properties and cellular behavior were examined.Immediate subcutaneous implantation in rabbits was con-ducted to observe its ectopic osteogenic induction effect.Successfully fabricated P34HB ultrafine fiber slow-release sys-tem.Charact ization med.theuniform distribution of HUCMSCs and inducing components within the scaffold,with no chemical reactions affecting the active components.In vitro tests showcased a prolonged release of DEX and ASP,while biocompatibility assays highlighted the scaffold's suitability for cellular growth.Alizarin Red,type I collagen,and osteopontin(OPN)staining verifed the scaffold's potent osteogenic induction effect on HUCMsCs.Notably,immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks.These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction,marking a promising advancement in bone tissue engineering.展开更多
Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produce...Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions.Mechanistically,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors.Disruption of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.展开更多
基金supported by National Natural Science Foundation of China[81960416(C.Y.)and 82260428(L.Y.)]Department of Science and Technology of Guizhou Province[2020]6013-2(C.Y.)+1 种基金Doctor start-up Fund of Affiliated Hospital of Guizhou Medical University[gyfybsky-2022-13(L.Y.)]Excellent Reserve talents Fund of Affiliated Hospital of Guizhou Medical University[gyfyxkrc-2023-11(L.Y.)].
文摘This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(P34HB)ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells(HUCMSCs).Utilizing dual-nozzle and cell electrospinning techniques,the system encapsulates L-ascorbic acid-2-phosphate magnesium(AsP),βB-glycerophosphate sodium and dexamethasone(DEX)within the'fbers,ensuring sustained osteogenic differentiation.The scaffold's morphology,characterization,hydrophilicity,mechanical properties and cellular behavior were examined.Immediate subcutaneous implantation in rabbits was con-ducted to observe its ectopic osteogenic induction effect.Successfully fabricated P34HB ultrafine fiber slow-release sys-tem.Charact ization med.theuniform distribution of HUCMSCs and inducing components within the scaffold,with no chemical reactions affecting the active components.In vitro tests showcased a prolonged release of DEX and ASP,while biocompatibility assays highlighted the scaffold's suitability for cellular growth.Alizarin Red,type I collagen,and osteopontin(OPN)staining verifed the scaffold's potent osteogenic induction effect on HUCMsCs.Notably,immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks.These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction,marking a promising advancement in bone tissue engineering.
基金supported by the National Natural Science Foundation of China(No.82130022,31925021)the National Key Research and Development Program of China(No.2018YFA0800700 and 2022YFC3401500).
文摘Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions.Mechanistically,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors.Disruption of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.