Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD)has emerged as a predominant cause of chronic liver disease globally,with its prevalence rising steadily each year.If left untreated,MASLD may progress to...Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD)has emerged as a predominant cause of chronic liver disease globally,with its prevalence rising steadily each year.If left untreated,MASLD may progress to metabolic dysfunction in associated steatohepatitis(MASH),a more severe condition that can irreversibly advance to liver fibrosis,cirrhosis,and even hepatocyte carcinoma(HCC).Recent studies have illuminated a pivotal link between dysregulated cholesterol metabolism and the pathogenesis and severity of MASLD.This underscores the critical need for a comprehensive exploration of the regulatory mechanisms underlying hepatic cholesterol metabolism in MASLD,as such insights could unveil new therapeutic targets and pave the way for early diagnosis and effective prevention strategies.Cyclocarya paliurus(Batal.)Iljinskaja,a plant known for both medicinal and dietary applications,has demonstrated diverse pharmacological properties,including hypoglycemic,lipid-regulating,and hepatoprotective effects.This study aimed to investigate the hypolipidemic and hepatoprotective activities of Cyclocarya paliurus extract(CCE)in a murine model of MASLD induced by a methionine-choline-deficient(MCD)diet.Simvastatin was employed as a positive control drug,while various doses of CCE were administered to assess its therapeutic potential.Meanwhile,the control and model groups received 0.5%sodium carboxymethyl cellulose(CMC-Na)once daily for 6 weeks.At the end of the treatment period,blood and liver samples were collected for biochemical analysis,histopathological assessment,and gene expression profiling.The findings revealed that CCE significantly reduced serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)while enhancing the activities of cholinesterase(CHE)and high-density lipoprotein cholesterol(HDL-C).In liver tissues,CCE markedly decreased the levels of total cholesterol(TC)and triglycerides(TG),while simultaneously increasing hepatic HDL-C content.Histological analyses showed notable alleviation of pathological liver damage in CCE-treated mice.Molecular studies further demonstrated that CCE downregulated the expression of key genes and proteins involved in cholesterol synthesis,including SREBP2,LDLR,and HMGCR.Concurrently,it upregulated the expression of genes and proteins related to cholesterol transport,such as ABCG5 and ABCG8.Additionally,CCE mitigated inflammation by improving the expression levels of pro-inflammatory cytokines,including TNF-α and IL-6,and modulated oxidative stress markers,such as NRF2,KEAP1,and NQO1.Protein expression analyses revealed reduced levels of IL-6 and IL-1β,further corroborating its anti-inflammatory effects.In summary,C.paliurus exhibited potent hepatoprotective effects in MCD-induced MASLD mice.These protective mechanisms were closely linked to the upregulation of cholesterol transporters ABCG5/8 and the modulation of sterol regulatory element-binding protein 2(SREBP2).This study highlighted the therapeutic potential of C.paliurus as a promising intervention for MASLD and underscored its role in regulating cholesterol metabolism and mitigating inflammation and oxidative stress.展开更多
目的探究中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病的相关性,并对一些相关脂质和脂蛋白水平进行研究,探究其与冠心病的关系。方法收集290例冠心病、198例非冠心病及331例健康正常人的血样,采用核酸自动提取仪提取基因组DNA,MassA...目的探究中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病的相关性,并对一些相关脂质和脂蛋白水平进行研究,探究其与冠心病的关系。方法收集290例冠心病、198例非冠心病及331例健康正常人的血样,采用核酸自动提取仪提取基因组DNA,MassARRAY时间飞行质谱技术分析rs4299376基因型,并测定所有研究对象血脂水平,对比分析各组人群基因多态性及血脂水平差异。结果中国人群ABCG5/ABCG8基因rs4299376多态性在冠心病组与非冠心病组以及健康对照组之间的分布差异无统计学意义。在总体和男性患者中,脂质水平与冠心病没有相关性;但在女性患者中,冠心病患者三酰甘油(TG)及总胆固醇(TC)水平比非冠心病患者高,差异有统计学意义(TG:2.23±1.05 vs 1.84±1.03,P=0.01;TC:4.79±1.17 vs 4.36±1.03,P=0.01)。根据年龄进行分层分析,≥60岁人群中,冠心病患者高密度脂蛋白(HDL)水平比非冠心病患者低(1.09±0.23 vs 1.16±0.25,P=0.03)。结论中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病可能关系不大;女性冠心病患者较非冠心病患者具有更高的TC和TG水平,60岁及以上的冠心病患者较非冠心病患者具有更低的HDL水平。展开更多
ABCG转运蛋白是ABC蛋白家族最庞大的亚族,广泛存在于植物体内。ABCG亚族主要由半分子转运蛋白WBC(white-brown complex)和全分子转运蛋白PDR(pleiotropic drug resistance)组成,其底物类型广泛,包括抗生素、植物激素、木质素单体、脂质...ABCG转运蛋白是ABC蛋白家族最庞大的亚族,广泛存在于植物体内。ABCG亚族主要由半分子转运蛋白WBC(white-brown complex)和全分子转运蛋白PDR(pleiotropic drug resistance)组成,其底物类型广泛,包括抗生素、植物激素、木质素单体、脂质及次生代谢产物等,涉及植物生命周期中的多种代谢活动。本文综述了植物ABCG转运蛋白的分子特性、结构及功能方面的研究进展,并对今后有关该蛋白的主要研究方向做了展望。展开更多
背景与目的:三磷酸腺苷结合盒转运体成员ABCG2(ATP-binding cassette superfamily G member2)是源于造血干细胞的标志物之一,其在神经胶质瘤发生发展相关组织和细胞中的表达情况还不清楚。本研究检测ABCG2在不同恶性程度人脑胶质瘤组织...背景与目的:三磷酸腺苷结合盒转运体成员ABCG2(ATP-binding cassette superfamily G member2)是源于造血干细胞的标志物之一,其在神经胶质瘤发生发展相关组织和细胞中的表达情况还不清楚。本研究检测ABCG2在不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体中的表达情况并分析其意义。方法:制作布有不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体等的组织芯片,用免疫组化方法检测ABCG2在组织芯片中的表达情况。结果:在71例人脑胶质瘤组织标本中ABCG2的阳性率为26.8%,其中Ⅰ级11.1%,Ⅱ级8.0%,Ⅲ级43.5%,Ⅳ级42.9%;Ⅰ～Ⅱ级与Ⅲ～Ⅳ级相比差异具有统计学意义(%2=10.710,P=0.001)。在神经干细胞、裸小鼠移植瘤、胶质瘤干细胞球体表达率为100%。在多种正常组织中亦有不同程度的表达。在胶质瘤临床标本中ABCG2阳性细胞呈亲血管分布。结论:ABCG2在胶质瘤干细胞、恶性程度高的胶质瘤组织标本和移植瘤组织中高表达,并且呈亲血管分布。展开更多
文摘目的通过动物实验和体外细胞实验探讨SAK-HV蛋白降胆固醇的机制。方法以0.5mg/kg浓度的SAK-HV蛋白治疗高脂喂养的Apo E-/-C57小鼠,酶法检测Apo E-/-C57小鼠血脂水平,定量PCR法(real-time quantitative PCR,q PCR)和蛋白质印迹(Western blot)法检测小肠ABCG5和ABCG8 m RNA和蛋白的表达水平。100μg/ml的SAK-HV蛋白作用caco-2细胞不同时间后,NBD胆固醇作为荧光探针检测SAK-HV蛋白对caco-2细胞胆固醇吸收的影响,q-PCR和Western blot法检测SAK-HV蛋白对caco-2细胞ABCG5和ABCG8 m RNA和蛋白表达水平的影响。结果 SAK-HV蛋白可以降低高脂喂养的Apo E-/-C57小鼠的血清胆固醇水平,同时上调小肠ABCG5和ABCG8 m RNA和蛋白的表达水平。体外实验表明,SAK-HV蛋白可以抑制caco-2细胞胆固醇的吸收,同时上调ABCG5和ABCG8 m RNA和蛋白的表达水平。结论 SAK-HV蛋白通过上调ABCG5和ABCG8的表达抑制小肠胆固醇的吸收从而降低血清胆固醇水平。
基金National Key Research and Development Program of China(Grant No.2022YFC3501700)the Beijing Municipal Natural Science Foundation(Grant No.7144219).
文摘Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD)has emerged as a predominant cause of chronic liver disease globally,with its prevalence rising steadily each year.If left untreated,MASLD may progress to metabolic dysfunction in associated steatohepatitis(MASH),a more severe condition that can irreversibly advance to liver fibrosis,cirrhosis,and even hepatocyte carcinoma(HCC).Recent studies have illuminated a pivotal link between dysregulated cholesterol metabolism and the pathogenesis and severity of MASLD.This underscores the critical need for a comprehensive exploration of the regulatory mechanisms underlying hepatic cholesterol metabolism in MASLD,as such insights could unveil new therapeutic targets and pave the way for early diagnosis and effective prevention strategies.Cyclocarya paliurus(Batal.)Iljinskaja,a plant known for both medicinal and dietary applications,has demonstrated diverse pharmacological properties,including hypoglycemic,lipid-regulating,and hepatoprotective effects.This study aimed to investigate the hypolipidemic and hepatoprotective activities of Cyclocarya paliurus extract(CCE)in a murine model of MASLD induced by a methionine-choline-deficient(MCD)diet.Simvastatin was employed as a positive control drug,while various doses of CCE were administered to assess its therapeutic potential.Meanwhile,the control and model groups received 0.5%sodium carboxymethyl cellulose(CMC-Na)once daily for 6 weeks.At the end of the treatment period,blood and liver samples were collected for biochemical analysis,histopathological assessment,and gene expression profiling.The findings revealed that CCE significantly reduced serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)while enhancing the activities of cholinesterase(CHE)and high-density lipoprotein cholesterol(HDL-C).In liver tissues,CCE markedly decreased the levels of total cholesterol(TC)and triglycerides(TG),while simultaneously increasing hepatic HDL-C content.Histological analyses showed notable alleviation of pathological liver damage in CCE-treated mice.Molecular studies further demonstrated that CCE downregulated the expression of key genes and proteins involved in cholesterol synthesis,including SREBP2,LDLR,and HMGCR.Concurrently,it upregulated the expression of genes and proteins related to cholesterol transport,such as ABCG5 and ABCG8.Additionally,CCE mitigated inflammation by improving the expression levels of pro-inflammatory cytokines,including TNF-α and IL-6,and modulated oxidative stress markers,such as NRF2,KEAP1,and NQO1.Protein expression analyses revealed reduced levels of IL-6 and IL-1β,further corroborating its anti-inflammatory effects.In summary,C.paliurus exhibited potent hepatoprotective effects in MCD-induced MASLD mice.These protective mechanisms were closely linked to the upregulation of cholesterol transporters ABCG5/8 and the modulation of sterol regulatory element-binding protein 2(SREBP2).This study highlighted the therapeutic potential of C.paliurus as a promising intervention for MASLD and underscored its role in regulating cholesterol metabolism and mitigating inflammation and oxidative stress.
文摘目的探究中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病的相关性,并对一些相关脂质和脂蛋白水平进行研究,探究其与冠心病的关系。方法收集290例冠心病、198例非冠心病及331例健康正常人的血样,采用核酸自动提取仪提取基因组DNA,MassARRAY时间飞行质谱技术分析rs4299376基因型,并测定所有研究对象血脂水平,对比分析各组人群基因多态性及血脂水平差异。结果中国人群ABCG5/ABCG8基因rs4299376多态性在冠心病组与非冠心病组以及健康对照组之间的分布差异无统计学意义。在总体和男性患者中,脂质水平与冠心病没有相关性;但在女性患者中,冠心病患者三酰甘油(TG)及总胆固醇(TC)水平比非冠心病患者高,差异有统计学意义(TG:2.23±1.05 vs 1.84±1.03,P=0.01;TC:4.79±1.17 vs 4.36±1.03,P=0.01)。根据年龄进行分层分析,≥60岁人群中,冠心病患者高密度脂蛋白(HDL)水平比非冠心病患者低(1.09±0.23 vs 1.16±0.25,P=0.03)。结论中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病可能关系不大;女性冠心病患者较非冠心病患者具有更高的TC和TG水平,60岁及以上的冠心病患者较非冠心病患者具有更低的HDL水平。
文摘ABCG转运蛋白是ABC蛋白家族最庞大的亚族,广泛存在于植物体内。ABCG亚族主要由半分子转运蛋白WBC(white-brown complex)和全分子转运蛋白PDR(pleiotropic drug resistance)组成,其底物类型广泛,包括抗生素、植物激素、木质素单体、脂质及次生代谢产物等,涉及植物生命周期中的多种代谢活动。本文综述了植物ABCG转运蛋白的分子特性、结构及功能方面的研究进展,并对今后有关该蛋白的主要研究方向做了展望。
文摘背景与目的:三磷酸腺苷结合盒转运体成员ABCG2(ATP-binding cassette superfamily G member2)是源于造血干细胞的标志物之一,其在神经胶质瘤发生发展相关组织和细胞中的表达情况还不清楚。本研究检测ABCG2在不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体中的表达情况并分析其意义。方法:制作布有不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体等的组织芯片,用免疫组化方法检测ABCG2在组织芯片中的表达情况。结果:在71例人脑胶质瘤组织标本中ABCG2的阳性率为26.8%,其中Ⅰ级11.1%,Ⅱ级8.0%,Ⅲ级43.5%,Ⅳ级42.9%;Ⅰ～Ⅱ级与Ⅲ～Ⅳ级相比差异具有统计学意义(%2=10.710,P=0.001)。在神经干细胞、裸小鼠移植瘤、胶质瘤干细胞球体表达率为100%。在多种正常组织中亦有不同程度的表达。在胶质瘤临床标本中ABCG2阳性细胞呈亲血管分布。结论:ABCG2在胶质瘤干细胞、恶性程度高的胶质瘤组织标本和移植瘤组织中高表达,并且呈亲血管分布。
