BACKGROUND Nonalcoholic fatty liver disease(NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis(NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeo...BACKGROUND Nonalcoholic fatty liver disease(NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis(NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid(UDCA)play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein(SREBP) 1 c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid metabolism.AIM To investigate the functional mechanism of UDCA in an oleic acid(OA)-induced cellular model of NAFLD.METHODS The cellular model of NAFLD was established using OA and treated with UDCA.First, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase(ALT), gamma-glutamyl transpeptidase(GGT), and aspartate aminotransferase(AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western blot.RESULTS In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations(especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with OA.CONCLUSION Our findings demonstrate the effect of UDCA in improving NAFLD. UDCA attenuates OA-induced hepatic steatosis mainly by regulation of AKT/mTOR/SREBP-1 signal transduction.展开更多
Epitaxial growth and structural characteristics of metastableβ-In2Se3 thin films on H-terminated Si(111)substrates are studied.The In2Se3 thin films grown below theβ-to-αphase transition temperature(453 K)are chara...Epitaxial growth and structural characteristics of metastableβ-In2Se3 thin films on H-terminated Si(111)substrates are studied.The In2Se3 thin films grown below theβ-to-αphase transition temperature(453 K)are characterized to be strainedβ-In2Se3 mixed with significantγ-In2Se3 phases.The pure-phased single-crystallineβ-In2Se3 can be reproducibly achieved by in situ annealing the as-deposited poly-crystalline In2Se3 within the phase equilibrium temperature window ofβ-In2Se3.It is suggeted that the observedγ-to-βphase transition triggered by quite a low annealing temperature should be a rather lowered phase transition barrier of the epitaxy-stabilized In2Se3 thin-film system at a state far from thermodynamic equilibrium.展开更多
Objective:Limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese population.Methods:We analyzed laboratory data from a previously published randomized,double-...Objective:Limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese population.Methods:We analyzed laboratory data from a previously published randomized,double-blind phase III trial(NCT03912259)to provide further insight into the safety of dupilumab in Chinese adults with moderate to severe AD.The trial participants received either 300 mg of dupilumab or placebo every 2 weeks for 16 weeks.Hematology,blood chemistry,serum thymus and activation-regulated chemokine(TARC),and total immunoglobulin E(IgE)were evaluated.Results:In total,82 participants received dupilumab and 83 received placebo.With the exception of eosinophil counts of>0.8×109/L,which were found less frequently with dupilumab(9.8%)than with placebo(18.7%),the hematology and blood chemistry values were generally stable in both treatment groups.There were no clinically significant differences between the dupilumab and placebo groups,and no participants developed treatment-emergent abnormalities of potential clinical significance.However,compared with placebo,greater decreases in serum lactate dehydrogenase(mean change,−97.4 vs.−33.5 IU/L),TARC(median percent change,−78.6%vs.−30.8%),and total IgE(median percent change,−53.4%vs.−0.2%)were observed with dupilumab than placebo at week 16.Conclusion:Dupilumab demonstrated a favorable laboratory safety profile in Chinese adults with moderate to severe AD.展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province,China,No.LQ19H290001
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis(NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid(UDCA)play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein(SREBP) 1 c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid metabolism.AIM To investigate the functional mechanism of UDCA in an oleic acid(OA)-induced cellular model of NAFLD.METHODS The cellular model of NAFLD was established using OA and treated with UDCA.First, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase(ALT), gamma-glutamyl transpeptidase(GGT), and aspartate aminotransferase(AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western blot.RESULTS In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations(especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with OA.CONCLUSION Our findings demonstrate the effect of UDCA in improving NAFLD. UDCA attenuates OA-induced hepatic steatosis mainly by regulation of AKT/mTOR/SREBP-1 signal transduction.
基金Project supported by the National Key Research and Development Program of China(Grant Nos.2018YFA0306102 and 2018YFA0306703)the National Natural Science Foundation of China(Grant Nos.61474014 and U1601208)the Sichuan Science and Technology Program,China(Grant Nos.2019YJ0202 and 20GJHZ0229).
文摘Epitaxial growth and structural characteristics of metastableβ-In2Se3 thin films on H-terminated Si(111)substrates are studied.The In2Se3 thin films grown below theβ-to-αphase transition temperature(453 K)are characterized to be strainedβ-In2Se3 mixed with significantγ-In2Se3 phases.The pure-phased single-crystallineβ-In2Se3 can be reproducibly achieved by in situ annealing the as-deposited poly-crystalline In2Se3 within the phase equilibrium temperature window ofβ-In2Se3.It is suggeted that the observedγ-to-βphase transition triggered by quite a low annealing temperature should be a rather lowered phase transition barrier of the epitaxy-stabilized In2Se3 thin-film system at a state far from thermodynamic equilibrium.
基金The phase III trial on which this subanalysis is based (NCT03912259) was sponsored by Sanofi. Medical writing assistance with the preparation of this article was also funded by Sanofi.
文摘Objective:Limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese population.Methods:We analyzed laboratory data from a previously published randomized,double-blind phase III trial(NCT03912259)to provide further insight into the safety of dupilumab in Chinese adults with moderate to severe AD.The trial participants received either 300 mg of dupilumab or placebo every 2 weeks for 16 weeks.Hematology,blood chemistry,serum thymus and activation-regulated chemokine(TARC),and total immunoglobulin E(IgE)were evaluated.Results:In total,82 participants received dupilumab and 83 received placebo.With the exception of eosinophil counts of>0.8×109/L,which were found less frequently with dupilumab(9.8%)than with placebo(18.7%),the hematology and blood chemistry values were generally stable in both treatment groups.There were no clinically significant differences between the dupilumab and placebo groups,and no participants developed treatment-emergent abnormalities of potential clinical significance.However,compared with placebo,greater decreases in serum lactate dehydrogenase(mean change,−97.4 vs.−33.5 IU/L),TARC(median percent change,−78.6%vs.−30.8%),and total IgE(median percent change,−53.4%vs.−0.2%)were observed with dupilumab than placebo at week 16.Conclusion:Dupilumab demonstrated a favorable laboratory safety profile in Chinese adults with moderate to severe AD.
