Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy pre...Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.展开更多
Silicon anodes are considered to have great prospects for use in batteries;however,many of their defects still need to be improved.The preparation of hybrid materials based on porous carbon is one of the effective way...Silicon anodes are considered to have great prospects for use in batteries;however,many of their defects still need to be improved.The preparation of hybrid materials based on porous carbon is one of the effective ways to alleviate the adverse impact resulting from the volume change and the inferior electronic conductivity of a silicon electrode.Herein,a chain-like carbon cluster structure is prepared,in which MOF-derived porous carbon acts as a shell structure to integrally encapsulate Si nanoparticles,and CNTs play a role in connecting carbon shells.Based on the exclusive structure,the carbon shell can accommodate the volume expansion more effectively,and CNTs can improve the overall stability and conductivity.The resulting composite reveals excellent rate capacity and enhanced cycling stability;in particular,a capacity of 732 mA·h·g^(-1) at 2 A·g^(-1) is achieved with a reservation rate of 72.3% after cycling 100 times at 1 A·g^(-1).展开更多
OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho.logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel.lular carcinoma.The purpose of thi...OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho.logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel.lular carcinoma.The purpose of this study was to determine whether Ganoderma lucidum polysaccha.ride peptide(GLPP) has therapeutic effect on NAFLD.METHODS ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic path.ways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophospholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7 A1,CYP8 B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1 c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepato.cytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a therapeutic drug for NAFLD.展开更多
基金Beijing Natural Science Foundation,Grant/Award Number:L222145 and L222030Emerging Engineering Interdisciplinary Project and the Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2022XGK008Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation,Grant/Award Number:BMU2022PY010。
文摘Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.
基金financially supported by the“Light of West China”Program of the Chinese Academy of Sciences.
文摘Silicon anodes are considered to have great prospects for use in batteries;however,many of their defects still need to be improved.The preparation of hybrid materials based on porous carbon is one of the effective ways to alleviate the adverse impact resulting from the volume change and the inferior electronic conductivity of a silicon electrode.Herein,a chain-like carbon cluster structure is prepared,in which MOF-derived porous carbon acts as a shell structure to integrally encapsulate Si nanoparticles,and CNTs play a role in connecting carbon shells.Based on the exclusive structure,the carbon shell can accommodate the volume expansion more effectively,and CNTs can improve the overall stability and conductivity.The resulting composite reveals excellent rate capacity and enhanced cycling stability;in particular,a capacity of 732 mA·h·g^(-1) at 2 A·g^(-1) is achieved with a reservation rate of 72.3% after cycling 100 times at 1 A·g^(-1).
基金supported by National Natural Science Foundation of China(8133007481620108029+1 种基金81261160507) Beijing Natural Science Foundation(7172113)
文摘OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho.logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel.lular carcinoma.The purpose of this study was to determine whether Ganoderma lucidum polysaccha.ride peptide(GLPP) has therapeutic effect on NAFLD.METHODS ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic path.ways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophospholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7 A1,CYP8 B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1 c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepato.cytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a therapeutic drug for NAFLD.
