Aim To investigate the protective effects of gentiopicroside (GPS) on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol (5 g · kg^-11 of body weight) by gavage every 12 h for a total of...Aim To investigate the protective effects of gentiopicroside (GPS) on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol (5 g · kg^-11 of body weight) by gavage every 12 h for a total of three do- ses to induce acute fatty liver. GPS (40 or 80 mg · kg^-1 ) was garaged with ethanol simultaneously for three doses. Administration of GPS significantly prevented the increases of serum ALT and AST caused by ethanol, as well as se- rum and hepatic TG. Results GPS could significantly prevent ethanol-induced hepatic steatosis and necrosis by H&E and Oil Red O staining. GPS also significantly inhibited lipogenic genes including sterol regulatory element binding transcription factor 1 ( SREBP-1 ), fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC) in eth- anol-treated mice. Additionally, GPS possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through inducing the phosphorylation of AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1). Af- ter treatment with GPS, peroxisome proliferator-activated receptor eL (PPARoL) protein expression in mouse liver was recovered as that level of normal mice. Ethanol treatment evoked P2X7r and caspase-1 protein expression, while GPS significantly suppressed those protein expressions. GPS may be developed as a potential therapeutic can- didate for ethanol-induced hepatic steatosis and inflammation.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
Acupuncture has been shown to be effective on alcohol use disorder.However,the underlying mechanism remains poorly understood.To investigate the effects of Shenmen(HT7)acupoint on brain activation induced by cue-elici...Acupuncture has been shown to be effective on alcohol use disorder.However,the underlying mechanism remains poorly understood.To investigate the effects of Shenmen(HT7)acupoint on brain activation induced by cue-elicited alcohol craving,30 right-handed healthy light to moderate alcohol drinkers were recruited from the community.They were randomly assigned to undergo acupuncture either at HT7(experimental acupoint,n=15)or Jingqu(LU8,control acupoint,n=15)acupoints.This randomized controlled study was performed in Daegu Haany University and Daegu-Gyeongbuk Medical Innovation Foundation,Republic of Korea.Recruitment and data collection were conducted from December 2018 to May 2019.The results showed that after acupuncture at HT7 acupoint,the activation of orbitofrontal cortex and dorsolateral prefrontal cortex was greatly increased,while the activation of dorsolateral prefrontal cortex was obviously reduced,and subject's craving for alcohol was reduced when he/she seeing alcohol-related video clips involving various alcohols(beer,wine,or soju)or drinking scenarios.Acupuncture at HT7 more greatly reduced subject's alcohol cravings than acupuncture at LU8 acupoint.These findings suggest that acupuncture can improve the self-control of mild to moderate social drinkers through the activation of the orbitofrontal cortex and dorsolateral prefrontal cortex,thereby reducing the craving for alcohol.The study protocol was approved by the Institutional Review Board of Daegu Haany University Korean Medicine Hospital,Republic of Korea(approval No.DHUMC-D-18026-PRO-02)on November 30,2018.展开更多
目的评价膜结合O-酰基转移酶7(MBOAT7)rs641738多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)易感性的关系。方法围绕MBOAT7多态性与NAFLD相关性所实施的病例-对照研究开展文献检索,所涉及数据库有中国生物医...目的评价膜结合O-酰基转移酶7(MBOAT7)rs641738多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)易感性的关系。方法围绕MBOAT7多态性与NAFLD相关性所实施的病例-对照研究开展文献检索,所涉及数据库有中国生物医学数据库、PubMed、万方、中国知网及Web of Science。对发表时间在2018年4月20日(含)之前的相关文献进行检索。指定两名评价者独立完成对纳入文献的数据抽提工作。采用Revman 5.3和STAT 12.0软件进行Meta分析。结果共纳入6篇文献,含NAFLD患者2 365例,病例对照9 058例。Meta分析结果显示,在加性、显性、隐性或等位基因模型下,两组比较差异均无统计学意义(CC vs TT:OR=0.93;CC vs TC+TT:OR=0.96;CC+CT vs TT:OR=0.92;C vs T:OR=0.96)。依据种族不同进行亚族分析后,发现在高加索人和亚洲人中,MBOAT7 rs641738多态性与NAFLD发病率均无关联(P>0.05)。结论 MBOAT7 rs641738突变与NAFLD易感性无关联。展开更多
文摘Aim To investigate the protective effects of gentiopicroside (GPS) on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol (5 g · kg^-11 of body weight) by gavage every 12 h for a total of three do- ses to induce acute fatty liver. GPS (40 or 80 mg · kg^-1 ) was garaged with ethanol simultaneously for three doses. Administration of GPS significantly prevented the increases of serum ALT and AST caused by ethanol, as well as se- rum and hepatic TG. Results GPS could significantly prevent ethanol-induced hepatic steatosis and necrosis by H&E and Oil Red O staining. GPS also significantly inhibited lipogenic genes including sterol regulatory element binding transcription factor 1 ( SREBP-1 ), fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC) in eth- anol-treated mice. Additionally, GPS possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through inducing the phosphorylation of AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1). Af- ter treatment with GPS, peroxisome proliferator-activated receptor eL (PPARoL) protein expression in mouse liver was recovered as that level of normal mice. Ethanol treatment evoked P2X7r and caspase-1 protein expression, while GPS significantly suppressed those protein expressions. GPS may be developed as a potential therapeutic can- didate for ethanol-induced hepatic steatosis and inflammation.
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 Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT),No.2018R1A5A2025272(to CHY and MYL)。
文摘Acupuncture has been shown to be effective on alcohol use disorder.However,the underlying mechanism remains poorly understood.To investigate the effects of Shenmen(HT7)acupoint on brain activation induced by cue-elicited alcohol craving,30 right-handed healthy light to moderate alcohol drinkers were recruited from the community.They were randomly assigned to undergo acupuncture either at HT7(experimental acupoint,n=15)or Jingqu(LU8,control acupoint,n=15)acupoints.This randomized controlled study was performed in Daegu Haany University and Daegu-Gyeongbuk Medical Innovation Foundation,Republic of Korea.Recruitment and data collection were conducted from December 2018 to May 2019.The results showed that after acupuncture at HT7 acupoint,the activation of orbitofrontal cortex and dorsolateral prefrontal cortex was greatly increased,while the activation of dorsolateral prefrontal cortex was obviously reduced,and subject's craving for alcohol was reduced when he/she seeing alcohol-related video clips involving various alcohols(beer,wine,or soju)or drinking scenarios.Acupuncture at HT7 more greatly reduced subject's alcohol cravings than acupuncture at LU8 acupoint.These findings suggest that acupuncture can improve the self-control of mild to moderate social drinkers through the activation of the orbitofrontal cortex and dorsolateral prefrontal cortex,thereby reducing the craving for alcohol.The study protocol was approved by the Institutional Review Board of Daegu Haany University Korean Medicine Hospital,Republic of Korea(approval No.DHUMC-D-18026-PRO-02)on November 30,2018.
文摘目的评价膜结合O-酰基转移酶7(MBOAT7)rs641738多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)易感性的关系。方法围绕MBOAT7多态性与NAFLD相关性所实施的病例-对照研究开展文献检索,所涉及数据库有中国生物医学数据库、PubMed、万方、中国知网及Web of Science。对发表时间在2018年4月20日(含)之前的相关文献进行检索。指定两名评价者独立完成对纳入文献的数据抽提工作。采用Revman 5.3和STAT 12.0软件进行Meta分析。结果共纳入6篇文献,含NAFLD患者2 365例,病例对照9 058例。Meta分析结果显示,在加性、显性、隐性或等位基因模型下,两组比较差异均无统计学意义(CC vs TT:OR=0.93;CC vs TC+TT:OR=0.96;CC+CT vs TT:OR=0.92;C vs T:OR=0.96)。依据种族不同进行亚族分析后,发现在高加索人和亚洲人中,MBOAT7 rs641738多态性与NAFLD发病率均无关联(P>0.05)。结论 MBOAT7 rs641738突变与NAFLD易感性无关联。