BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and ...BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS According to the inclusion and exclusion criteria,27 patients with ALC and 24 healthy controls(HCs)were selected,and plasma and feces samples were collected.Liver function,blood routine,and other indicators were detected with automatic biochemical and blood routine analyzers.Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces.Also,the correlation between metabolites and clinical features was analyzed.RESULTS More than 300 common metabolites were identified in the plasma and feces of patients with ALC.Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways.Compared to HCs,patients with ALC had a higher level of glycocholic acid(GCA)and taurocholic acid(TCA)in plasma and a lower level of deoxycholic acid(DCA)in the feces,while L-threonine,L-phenylalanine,and L-tyrosine increased simultaneously in plasma and feces.GCA,TCA,L-methionine,L-phenylalanine,and L-tyrosine in plasma were positively correlated with total bilirubin(TBil),prothrombin time(PT),and maddrey discriminant function score(MDF)and negatively correlated with cholinesterase(CHE)and albumin(ALB).The DCA in feces was negatively correlated with TBil,MDF,and PT and positively correlated with CHE and ALB.Moreover,we established a P/S BA ratio of plasma primary bile acid(GCA and TCA)to fecal secondary bile acid(DCA),which was relevant to TBil,PT,and MDF score.CONCLUSION The enrichment of GCA,TCA,L-phenylalanine,L-tyrosine,and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC.These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.展开更多
Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential.The main reason is that malignant glioma holds key cluster cells,glioma stem cells(GSCs).GSCs contribute to tum...Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential.The main reason is that malignant glioma holds key cluster cells,glioma stem cells(GSCs).GSCs contribute to tumorigenesis,tumor progression,recurrence,and treatment resistance.Interferon-beta(IFN-β)is well known for its anti-proliferative efficacy in diverse cancers.IFN-βalso displayed potent antitumor effects in malignant glioma.IFN-βaffect both GSCs and Neural stem cells(NSCs)in the treatment of gliomas.However,the functional comparison,similar or different effects of IFN-βon GSCs and NSCs are rarely reported.Here,we studied the similarities and differences of the responses to IFN-βbetween human GSCs and normal NSCs.We found that IFN-βpreferentially inhibited GSCs over NSCs.The cell body and nucleus size of GSCs increased after IFN-βtreatment,and the genomic analysis revealed the enrichment of the upregulated immune response,cell adhesion genes and down regulated cell cycle,ribosome pathways.Several typical cyclin genes,including cyclin A2(CCNA2),cyclin B1(CCNB1),cyclin B2(CCNB2),and cyclin D1(CCND1),were significantly downregulated in GSCs after IFN-βstimulation.We also found that continuous IFN-βstimulation after passage further enhanced the inhibitory effect.Our study revealed how genetic diversity resulted in differential effects in response to IFN-βtreatment.These results may contribute to improve the applications of IFN-βin anti-cancer immunotherapy.In addition,these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.展开更多
基金Supported by National Key R&D Program of China,No.21YFC2301801Capital's Funds for Health Improvement and Research of China,No.2020-1-2171.
文摘BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS According to the inclusion and exclusion criteria,27 patients with ALC and 24 healthy controls(HCs)were selected,and plasma and feces samples were collected.Liver function,blood routine,and other indicators were detected with automatic biochemical and blood routine analyzers.Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces.Also,the correlation between metabolites and clinical features was analyzed.RESULTS More than 300 common metabolites were identified in the plasma and feces of patients with ALC.Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways.Compared to HCs,patients with ALC had a higher level of glycocholic acid(GCA)and taurocholic acid(TCA)in plasma and a lower level of deoxycholic acid(DCA)in the feces,while L-threonine,L-phenylalanine,and L-tyrosine increased simultaneously in plasma and feces.GCA,TCA,L-methionine,L-phenylalanine,and L-tyrosine in plasma were positively correlated with total bilirubin(TBil),prothrombin time(PT),and maddrey discriminant function score(MDF)and negatively correlated with cholinesterase(CHE)and albumin(ALB).The DCA in feces was negatively correlated with TBil,MDF,and PT and positively correlated with CHE and ALB.Moreover,we established a P/S BA ratio of plasma primary bile acid(GCA and TCA)to fecal secondary bile acid(DCA),which was relevant to TBil,PT,and MDF score.CONCLUSION The enrichment of GCA,TCA,L-phenylalanine,L-tyrosine,and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC.These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.
基金This work was supported by funds from the National Natural Science Foundation of China[31600819 to CCH,81901031 to HXX,32070862 and 31571058 to GZL]the Shanghai Municipal Population and Family Planning Commission[20174Y0216 to CCH]+2 种基金the Natural Science Foundation of Shanghai[19ZR1445400 to HXX]the National Key R&D Program of China[2019YFA0110300]the Shanghai Easter Scholar[8101219003 to GZL].
文摘Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential.The main reason is that malignant glioma holds key cluster cells,glioma stem cells(GSCs).GSCs contribute to tumorigenesis,tumor progression,recurrence,and treatment resistance.Interferon-beta(IFN-β)is well known for its anti-proliferative efficacy in diverse cancers.IFN-βalso displayed potent antitumor effects in malignant glioma.IFN-βaffect both GSCs and Neural stem cells(NSCs)in the treatment of gliomas.However,the functional comparison,similar or different effects of IFN-βon GSCs and NSCs are rarely reported.Here,we studied the similarities and differences of the responses to IFN-βbetween human GSCs and normal NSCs.We found that IFN-βpreferentially inhibited GSCs over NSCs.The cell body and nucleus size of GSCs increased after IFN-βtreatment,and the genomic analysis revealed the enrichment of the upregulated immune response,cell adhesion genes and down regulated cell cycle,ribosome pathways.Several typical cyclin genes,including cyclin A2(CCNA2),cyclin B1(CCNB1),cyclin B2(CCNB2),and cyclin D1(CCND1),were significantly downregulated in GSCs after IFN-βstimulation.We also found that continuous IFN-βstimulation after passage further enhanced the inhibitory effect.Our study revealed how genetic diversity resulted in differential effects in response to IFN-βtreatment.These results may contribute to improve the applications of IFN-βin anti-cancer immunotherapy.In addition,these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.
