Alcohol dehydrogenase 5(ADH5)is a member of medium-chain dehydro-genase/reductase family and takes part in cellular formaldehyde and S-nitrosoglutathione metabolic network.2-tridecanone(2-TD)is a toxic compound in man...Alcohol dehydrogenase 5(ADH5)is a member of medium-chain dehydro-genase/reductase family and takes part in cellular formaldehyde and S-nitrosoglutathione metabolic network.2-tridecanone(2-TD)is a toxic compound in many Solanaceae crops to defend against a variety of herbivory insects.In the broader context of insect development and pest control strategies,this study investigates how a new ADHS from Helicoverpa armigera(HaADH5)regulates the expression of CYP6B6,a gene involved in molting and metamorphosis,in response to 2-TD treatment.Cloning of the HaADH5 complementary DNA sequence revealed that its 1002 bp open reading frame encodes 334 amino acids with a predicted molecular weight of 36.5 kD.HaADH5 protein was purified in the Es-cherichia coli Transetta(pET32a-HaADH5)strain using a prokaryotic expression system.The ability of HaADH5 protein to interact with the 2-TD responsive region within the promoter of CYP6B6 was confirmed by an in vitro electrophoretic mobility shift assay and transcription activity validation in yeast.Finally,the expression levels of both HaADH5 and CYP6B6 were found to be significantly decreased in the midgut of 6th instar larvae after 48 h of treatment with 10 mg/g 2-TD artificial diet.These results indicate that upon 2-TD treatment of cotton bollworm,HaADHS regulates the expression of CYP6B6 by interacting with its promoter.As HaADH5 regulation of CYP6B6 expression may con-tribute to the larval xenobiotic detoxification,molting and metamorphosis,HaADH5 is a.candidate target for controlling the growth and development of cotton bollworm.展开更多
AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieve...AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.展开更多
It is well known that exposure to environmental stresses could enhance the adaptability of bacteria and up-regulate the expression of a variety of oxidative stress-related genes and antioxidant enzymes.It is unclear w...It is well known that exposure to environmental stresses could enhance the adaptability of bacteria and up-regulate the expression of a variety of oxidative stress-related genes and antioxidant enzymes.It is unclear whether the adaptability of microorganisms formed naturally in special environments could transfer to other organisms.The study aimed to evaluate the effects of untreated and ethanol-induced Lactococcus lactis intracellular extracts(U-IE and E-IE)on alcohol metabolism in mice.The positive effects of E-IE on alcohol metabolism in mice were revealed by the enhanced latency of loss of righting reflex(LORR),the reduced duration of LORR,the decrease of blood alcohol concentration,as well as the elevation of alcohol dehydrogenase(ADH)activities in the stomach and liver tissues.Furthermore,the potential benefits of E-IE on the liver were evaluated by biochemical parameters including the activities of serum transaminase,the levels of antioxidant enzymes,and the pathological changes of liver tissue.The present work put forward a new point that appropriate ethanol stress could enhance the intracellular ADH activity of L.lactis,and its intracellular extracts could continue to enhance alcohol metabolism in mice.展开更多
Objective:To explore the expression and prognostic significance of ADHs in Hepatocellular carcinoma(HCC).Methods:The clinical data in this study were obtained from The Cancer Genome Atlas(TCGA).The expression of ADHs ...Objective:To explore the expression and prognostic significance of ADHs in Hepatocellular carcinoma(HCC).Methods:The clinical data in this study were obtained from The Cancer Genome Atlas(TCGA).The expression of ADHs was differentially analyzed in normal liver tissues and HCC using the Metabolic gEne RApid Visualizer and the TCGA database,and the differentially expressed ADHs were selected for kaplan-meier survival analysis.Cox analysis was performed to select factors that may influence the prognosis of HCC and to verify independent risk factors for HCC patients.The interaction among ADHs was explored at the gene level and protein expression level through GeneMAMIA and STRING,and the functional enrichment analysis of ADH family was carried out using DAVID bioinformatics resources.Results:The expression of ADH1A,ADH1B,ADH1C,ADH4 and ADH7 in HCC is low.The low-expression groups of ADH1A,ADH1B,ADH1C and ADH4 had poor survival rates,which may be related to the poor prognosis of HCC patients.Univariate Cox regression analysis showed that the expression levels of ADH1A,ADH1C and ADH4,as well as the clinical stage,T stage and M stage of the tumor were closely related to the overall survival rate of the patients.Multivariate Cox regression analysis further suggested that the low expression of ADH1A,ADH1C and ADH4 was an independent risk factor affecting the prognosis of HCC patients.There is a pathway between ADH1A-ADH1B,ADH1B-ADH1C,ADH1A-ADH1C,and the ADHs is closely related to Esterase D and Aldehyde dehydrogenase.The ADHs is mainly involved in biological processes such as Ethanol oxidation and Retinol metabolism,and plays a biological role in Glycolysis/Gluconeogenesis,Chemical carcinogenesis and Metabolism of xenobiotics by cytochrome P450.Conclusion:ADH1A,ADH1C and ADH4 may be biomarkers for the prognosis of HCC,providing reference value for the practical application of ADHs in HCC.展开更多
基金This work was supported by the National Natural Science Foundation of China(31471781)Natural Science Foun-dation of Xinjiang Region in China(2016D01C042)Tianshan Cedar Project in 2017(2017xs20).
文摘Alcohol dehydrogenase 5(ADH5)is a member of medium-chain dehydro-genase/reductase family and takes part in cellular formaldehyde and S-nitrosoglutathione metabolic network.2-tridecanone(2-TD)is a toxic compound in many Solanaceae crops to defend against a variety of herbivory insects.In the broader context of insect development and pest control strategies,this study investigates how a new ADHS from Helicoverpa armigera(HaADH5)regulates the expression of CYP6B6,a gene involved in molting and metamorphosis,in response to 2-TD treatment.Cloning of the HaADH5 complementary DNA sequence revealed that its 1002 bp open reading frame encodes 334 amino acids with a predicted molecular weight of 36.5 kD.HaADH5 protein was purified in the Es-cherichia coli Transetta(pET32a-HaADH5)strain using a prokaryotic expression system.The ability of HaADH5 protein to interact with the 2-TD responsive region within the promoter of CYP6B6 was confirmed by an in vitro electrophoretic mobility shift assay and transcription activity validation in yeast.Finally,the expression levels of both HaADH5 and CYP6B6 were found to be significantly decreased in the midgut of 6th instar larvae after 48 h of treatment with 10 mg/g 2-TD artificial diet.These results indicate that upon 2-TD treatment of cotton bollworm,HaADHS regulates the expression of CYP6B6 by interacting with its promoter.As HaADH5 regulation of CYP6B6 expression may con-tribute to the larval xenobiotic detoxification,molting and metamorphosis,HaADH5 is a.candidate target for controlling the growth and development of cotton bollworm.
基金Supported by The Medical Faculty of the Heinrich Heine University Düsseldorf
文摘AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.
基金supported by the National Natural Science Foundation of China(81870093)the Research Project of People’s Liberation Army(BX115C007,BFP20C006)+1 种基金the Special Subject Funding of Zhengzhou Universitythe Natural Science Foundation of Henan Province for Outstanding Youth(202300410365)。
文摘It is well known that exposure to environmental stresses could enhance the adaptability of bacteria and up-regulate the expression of a variety of oxidative stress-related genes and antioxidant enzymes.It is unclear whether the adaptability of microorganisms formed naturally in special environments could transfer to other organisms.The study aimed to evaluate the effects of untreated and ethanol-induced Lactococcus lactis intracellular extracts(U-IE and E-IE)on alcohol metabolism in mice.The positive effects of E-IE on alcohol metabolism in mice were revealed by the enhanced latency of loss of righting reflex(LORR),the reduced duration of LORR,the decrease of blood alcohol concentration,as well as the elevation of alcohol dehydrogenase(ADH)activities in the stomach and liver tissues.Furthermore,the potential benefits of E-IE on the liver were evaluated by biochemical parameters including the activities of serum transaminase,the levels of antioxidant enzymes,and the pathological changes of liver tissue.The present work put forward a new point that appropriate ethanol stress could enhance the intracellular ADH activity of L.lactis,and its intracellular extracts could continue to enhance alcohol metabolism in mice.
基金supported by Wuhan Municipal Project of Scientific Problem Tackling(No.201161038342-02)。
文摘Objective:To explore the expression and prognostic significance of ADHs in Hepatocellular carcinoma(HCC).Methods:The clinical data in this study were obtained from The Cancer Genome Atlas(TCGA).The expression of ADHs was differentially analyzed in normal liver tissues and HCC using the Metabolic gEne RApid Visualizer and the TCGA database,and the differentially expressed ADHs were selected for kaplan-meier survival analysis.Cox analysis was performed to select factors that may influence the prognosis of HCC and to verify independent risk factors for HCC patients.The interaction among ADHs was explored at the gene level and protein expression level through GeneMAMIA and STRING,and the functional enrichment analysis of ADH family was carried out using DAVID bioinformatics resources.Results:The expression of ADH1A,ADH1B,ADH1C,ADH4 and ADH7 in HCC is low.The low-expression groups of ADH1A,ADH1B,ADH1C and ADH4 had poor survival rates,which may be related to the poor prognosis of HCC patients.Univariate Cox regression analysis showed that the expression levels of ADH1A,ADH1C and ADH4,as well as the clinical stage,T stage and M stage of the tumor were closely related to the overall survival rate of the patients.Multivariate Cox regression analysis further suggested that the low expression of ADH1A,ADH1C and ADH4 was an independent risk factor affecting the prognosis of HCC patients.There is a pathway between ADH1A-ADH1B,ADH1B-ADH1C,ADH1A-ADH1C,and the ADHs is closely related to Esterase D and Aldehyde dehydrogenase.The ADHs is mainly involved in biological processes such as Ethanol oxidation and Retinol metabolism,and plays a biological role in Glycolysis/Gluconeogenesis,Chemical carcinogenesis and Metabolism of xenobiotics by cytochrome P450.Conclusion:ADH1A,ADH1C and ADH4 may be biomarkers for the prognosis of HCC,providing reference value for the practical application of ADHs in HCC.
