Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy ...Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy of Scytosiphon lomentaria fucoidan(SLF)in alleviating alcohol-induced liver injury was evaluated in a mouse model.It showed that SLF increased body weight and colon length,while reducing liver index,serum lipid,alanine aminotransferase,and aspartate aminotransferase in alcohol-treated mice.SLF inhibited inflammatory response in the liver by reducing inflammatory infiltration and the levels of pro-inflammatory cytokines.It can be associated with the alleviation of oxidative stress and the inhibition of the nuclear factor-κB pathway.SLF modulated alcohol-induced dysbiosis of gut microbiota,including a reduction in Bacteroidetes and Proteobacteria,and improved metabolites profile,primarily affecting short chain fatty acids and amino acids metabolism.In addition,SLF reduced the level of total bile acids,regulated the profile of bile acids,and increased the levels of farnesoid X receptor(FXR)and AMP-activated protein kinase(AMPK),suggesting that SLF can alleviate alcohol-induced liver injury by regulating bile acid-FXR/AMPK pathway.This study suggests that SLF holds the potential to alleviate the adverse effect of alcohol on the liver via the gut-liver axis.展开更多
抑郁症是一种以心境障碍为主要特征的精神类疾病,对人类的身心健康构成了重大的威胁。近年来,法尼醇X受体(farnesoid X receptor,FXR)已被发现在大脑海马体等脑区中表达,并与抑郁症的发病密切相关。其还可影响下游靶标环磷酸腺苷反应元...抑郁症是一种以心境障碍为主要特征的精神类疾病,对人类的身心健康构成了重大的威胁。近年来,法尼醇X受体(farnesoid X receptor,FXR)已被发现在大脑海马体等脑区中表达,并与抑郁症的发病密切相关。其还可影响下游靶标环磷酸腺苷反应元件结合蛋白(cAMP response element binding protein,CREB)-脑源性神经营养因子(brain-derived-neurotrophic factor,BDNF)信号通路,有望作为治疗抑郁症的新靶点。本文分析海马FXR如何调控CREB-BDNF信号通路,并总结与抑郁症发病机制相关的最新研究进展,以期为抑郁症的药物研发和临床治疗提供精准靶向的思路。展开更多
非酒精性脂肪性肝病(NAFLD)可进展至非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH),进一步可演变成肝硬化,甚至是肝细胞癌(HCC)^([1,2])。研究发现NAFLD与肥胖、糖尿病、高血压、血脂异常和代谢综合征等代谢功能障碍密切相关...非酒精性脂肪性肝病(NAFLD)可进展至非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH),进一步可演变成肝硬化,甚至是肝细胞癌(HCC)^([1,2])。研究发现NAFLD与肥胖、糖尿病、高血压、血脂异常和代谢综合征等代谢功能障碍密切相关^([3])。因此,亚太肝病研究学会建议将NAFLD更名为代谢相关脂肪性肝病(MAFLD)。胆汁酸是NAFLD发病机制中的关键信号分子,在脂肪的吸收和新陈代谢的调节方面发挥多效性作用^([4])。胆汁酸能通过激活相应受体调节代谢和炎症反应^([5])。法尼醇X受体(farnesoid X receptor,FXR)作为胆汁酸受体之一,在肝脏和肠道高度表达,激活FXR能调节胆汁酸和脂质代谢,维持葡萄糖稳态,预防肝纤维化,成为治疗NAFLD的重要靶点^([6,7])。展开更多
文摘Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy of Scytosiphon lomentaria fucoidan(SLF)in alleviating alcohol-induced liver injury was evaluated in a mouse model.It showed that SLF increased body weight and colon length,while reducing liver index,serum lipid,alanine aminotransferase,and aspartate aminotransferase in alcohol-treated mice.SLF inhibited inflammatory response in the liver by reducing inflammatory infiltration and the levels of pro-inflammatory cytokines.It can be associated with the alleviation of oxidative stress and the inhibition of the nuclear factor-κB pathway.SLF modulated alcohol-induced dysbiosis of gut microbiota,including a reduction in Bacteroidetes and Proteobacteria,and improved metabolites profile,primarily affecting short chain fatty acids and amino acids metabolism.In addition,SLF reduced the level of total bile acids,regulated the profile of bile acids,and increased the levels of farnesoid X receptor(FXR)and AMP-activated protein kinase(AMPK),suggesting that SLF can alleviate alcohol-induced liver injury by regulating bile acid-FXR/AMPK pathway.This study suggests that SLF holds the potential to alleviate the adverse effect of alcohol on the liver via the gut-liver axis.
文摘抑郁症是一种以心境障碍为主要特征的精神类疾病,对人类的身心健康构成了重大的威胁。近年来,法尼醇X受体(farnesoid X receptor,FXR)已被发现在大脑海马体等脑区中表达,并与抑郁症的发病密切相关。其还可影响下游靶标环磷酸腺苷反应元件结合蛋白(cAMP response element binding protein,CREB)-脑源性神经营养因子(brain-derived-neurotrophic factor,BDNF)信号通路,有望作为治疗抑郁症的新靶点。本文分析海马FXR如何调控CREB-BDNF信号通路,并总结与抑郁症发病机制相关的最新研究进展,以期为抑郁症的药物研发和临床治疗提供精准靶向的思路。
文摘非酒精性脂肪性肝病(NAFLD)可进展至非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH),进一步可演变成肝硬化,甚至是肝细胞癌(HCC)^([1,2])。研究发现NAFLD与肥胖、糖尿病、高血压、血脂异常和代谢综合征等代谢功能障碍密切相关^([3])。因此,亚太肝病研究学会建议将NAFLD更名为代谢相关脂肪性肝病(MAFLD)。胆汁酸是NAFLD发病机制中的关键信号分子,在脂肪的吸收和新陈代谢的调节方面发挥多效性作用^([4])。胆汁酸能通过激活相应受体调节代谢和炎症反应^([5])。法尼醇X受体(farnesoid X receptor,FXR)作为胆汁酸受体之一,在肝脏和肠道高度表达,激活FXR能调节胆汁酸和脂质代谢,维持葡萄糖稳态,预防肝纤维化,成为治疗NAFLD的重要靶点^([6,7])。
