目的探讨茵陈蒿汤对代谢相关脂肪性肝病(MAFLD)小鼠LncMEG3/miR-21-5p/PPARα介导脂肪酸β氧化的影响。方法为探讨MAFLD差异表达的miRNAs,应用PubMed、Web of Science和中国知网3个电子数据库对以中英文发表的研究进行检索,采用随机效...目的探讨茵陈蒿汤对代谢相关脂肪性肝病(MAFLD)小鼠LncMEG3/miR-21-5p/PPARα介导脂肪酸β氧化的影响。方法为探讨MAFLD差异表达的miRNAs,应用PubMed、Web of Science和中国知网3个电子数据库对以中英文发表的研究进行检索,采用随机效应模型进行Meta分析。24只C57BL/6J小鼠,SPF级,采用随机数字表法将小鼠随机分为对照组、模型组和茵陈蒿汤组,共3组,每组8只。采用喂饲高脂饲料的方法对模型组和茵陈蒿汤组小鼠建立MAFLD模型。12周后,茵陈蒿汤组给予茵陈蒿汤灌胃,每日1次,连续4周。采用HE染色法和油红O染色法观察各组小鼠肝组织病理形态表现;全自动生化分析仪检测血清甘油三酯(TG)、总胆固醇(TC)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、高密度脂蛋白胆固(HDL-C)和低密度脂蛋白胆固醇(LDL-C);试剂盒检测小鼠肝脏甘油三酯(TG)和游离脂肪酸(FFA)水平;RT-qPCR法检测小鼠LncMEG3、miR-21-5p、miR-34a-5p、miR-122-5p、miR-192-5p、过氧化物酶体增殖物激活受体α(PPARα)、肉碱棕榈酰转移酶1A(CPT1A)、肉碱棕榈酰基转移酶2(CPT2)、中链酰基辅酶A脱氢酶(MCAD)、长链脂酰辅酶A脱氢酶(LCAD)、酰基辅酶A氧化酶1(ACOX1)和三羟酰辅酶A脱氢酶(EHHADH)mRNA水平蛋白表达水平。结果Meta分析结果显示,与健康对照组相比,MAFLD组miR-34a-5p、miR-122-5p、miR-192-5p、miR-21-5p、miR-451-5p水平显著升高。肝脏HE染色结果发现,模型组小鼠出现肝细胞肿胀,体积增大,有明显脂肪变性;与模型组相比,茵陈蒿汤组小鼠肝细胞体积肿胀明显降低,脂肪变性显著减少。肝脏油红O染色结果发现,与对照组相比,模型组肝脏可见大量橘红色脂滴,脂质沉积显著升高;茵陈蒿汤组可见少量脂肪变性,橘红色脂滴分布减少,肝脏脂质沉积情况明显改善。相较于对照组,模型组小鼠血清HDL-C、LDL-C、TG、TC、AST、ALT表达显著升高(P<0.05),肝脏TG和FFA水平均显著升高(P<0.05);相较于模型组,茵陈蒿汤组小鼠肝脏FFA和TG水平显著降低(P<0.05),血清AST、LDL-C、TG、ALT水平显著降低(P<0.05)。与对照组相比,模型组miR-21-5p、miR-34a-5p、miR-122-5p、miR-192-5p表达水平增高(P<0.05);与模型组相比,茵陈蒿汤组miR-21-5p、miR-34a-5p、miR-122-5p、miR-192-5p表达水平降低(P<0.05),miR-21-5p变化倍数(模型组/茵陈蒿汤组)最大。与对照组相比,模型组Lnc MEG3表达水平降低(P<0.05);与模型组相比,茵陈蒿汤组Lnc MEG3表达水平升高(P<0.05)。与对照组相比,模型组PPARα、CPT1A、CPT2、MCAD、LCAD、ACOX1、EHHADH mRNA和蛋白表达水平显著降低(P<0.05);与模型组相比,茵陈蒿汤组PPARα、CPT1A、CPT2、MCAD、LCAD、ACOX1、EHHADH mRNA和蛋白表达水平显著升高(P<0.05)。结论茵陈蒿汤可能通过调控Lnc MEG3/miR-21-5p/PPARα信号通路促进肝脏脂肪酸β氧化,从而达到防治MAFLD的作用。展开更多
[目的]探究Lnc-AC226118.1/miR-99b-5p/TRIB1信号通路对术后认知障碍大鼠神经细胞活性的影响。[方法]将术后认知障碍大鼠神经细胞分为3组:对照组、si NC组和si TRIB1组。通过CCK-8实验检测神经细胞增殖能力;通过细胞集落形成实验检测神...[目的]探究Lnc-AC226118.1/miR-99b-5p/TRIB1信号通路对术后认知障碍大鼠神经细胞活性的影响。[方法]将术后认知障碍大鼠神经细胞分为3组:对照组、si NC组和si TRIB1组。通过CCK-8实验检测神经细胞增殖能力;通过细胞集落形成实验检测神经细胞聚集活性;通过流式细胞数检测神经细胞凋亡率;通过生物信息学分析Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴的结合位点;通过荧光素报告基因实验检测Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴的靶向作用关系。通过蛋白免疫印迹实验分析TRIB1的表达。通过实时荧光PCR实验检测miR-99b-5p的表达。[结果]与对照组、si NC组相比,si TRIB1组的神经细胞增殖和聚集活性增加(1.25±0.08 vs 1.36±0.11 vs 2.27±0.03;62.69±12.28 vs 57.36±13.59 vs 173.51±22.68;P<0.05),凋亡率降低(13.19%±0.29%vs 14.66%±0.52%vs 3.69%±0.08%;P<0.05)。Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴分子间有相互结合位点,且具有靶向调控关系。[结论]激活Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴能够提高术后认知障碍大鼠神经细胞活性,Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴有望成为术后认知障碍治疗的潜在靶点。展开更多
BACKGROUND Hepatitis C virus(HCV)infection and its consequent complications are undeniably a public health burden worldwide,particularly in Egypt.Emerging evidence suggests that many lncRNAs have relevant roles in vir...BACKGROUND Hepatitis C virus(HCV)infection and its consequent complications are undeniably a public health burden worldwide,particularly in Egypt.Emerging evidence suggests that many lncRNAs have relevant roles in viral infections and antiviral responses.AIM To investigate the expression profiles of circulating lncRNAGAS5,lncRNAHEIH,lncRNABISPR and mRNABST2 in naïve,treated and relapsed HCV Egyptian patients,to elucidate relation to HCV infection and their efficacy as innovative biomarkers for the diagnosis and prognosis of HCV GT4.METHODS One hundred and thirty HCV-infected Egyptian patients and 20 healthy controls were included in this study.Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Our results indicated that serum lncRNAGAS5 and LncRNABISPR were upregulated,whereas mRNA BST2 and LncRNA HEIH were downregulated in naïve patients.In contrast,HCV patients treated with sofosbuvir and simeprevir;with sofosbuvir and daclatasvir;or with sofosbuvir,daclatasvir and ribavirin exhibited lower levels of lncRNAGAS5 and lncRNABISPR with higher mRNABST2 compared to naïve patients.Notably,patients relapsed from sofosbuvir and simeprevir showed higher levels of these lncRNAs with lower mRNABST2 compared to treated patients.LncRNAGAS5 and lncRNABISPR were positively correlated with viral load and ALT at P<0.001,whereas mRNABST2 was negatively correlated with viral load at P<0.001 and ALT at P<0.05.Interestingly,a significant positive correlation between lncRNA HEIH and AFP was observed at P<0.001.CONCLUSION Differential expression of these RNAs suggests their involvement in HCV pathogenesis or antiviral response and highlights their promising roles in diagnosis and prognosis of HCV.展开更多
文摘[目的]探究Lnc-AC226118.1/miR-99b-5p/TRIB1信号通路对术后认知障碍大鼠神经细胞活性的影响。[方法]将术后认知障碍大鼠神经细胞分为3组:对照组、si NC组和si TRIB1组。通过CCK-8实验检测神经细胞增殖能力;通过细胞集落形成实验检测神经细胞聚集活性;通过流式细胞数检测神经细胞凋亡率;通过生物信息学分析Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴的结合位点;通过荧光素报告基因实验检测Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴的靶向作用关系。通过蛋白免疫印迹实验分析TRIB1的表达。通过实时荧光PCR实验检测miR-99b-5p的表达。[结果]与对照组、si NC组相比,si TRIB1组的神经细胞增殖和聚集活性增加(1.25±0.08 vs 1.36±0.11 vs 2.27±0.03;62.69±12.28 vs 57.36±13.59 vs 173.51±22.68;P<0.05),凋亡率降低(13.19%±0.29%vs 14.66%±0.52%vs 3.69%±0.08%;P<0.05)。Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴分子间有相互结合位点,且具有靶向调控关系。[结论]激活Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴能够提高术后认知障碍大鼠神经细胞活性,Lnc-AC226118.1/miR-99b-5p/TRIB1信号轴有望成为术后认知障碍治疗的潜在靶点。
文摘BACKGROUND Hepatitis C virus(HCV)infection and its consequent complications are undeniably a public health burden worldwide,particularly in Egypt.Emerging evidence suggests that many lncRNAs have relevant roles in viral infections and antiviral responses.AIM To investigate the expression profiles of circulating lncRNAGAS5,lncRNAHEIH,lncRNABISPR and mRNABST2 in naïve,treated and relapsed HCV Egyptian patients,to elucidate relation to HCV infection and their efficacy as innovative biomarkers for the diagnosis and prognosis of HCV GT4.METHODS One hundred and thirty HCV-infected Egyptian patients and 20 healthy controls were included in this study.Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Our results indicated that serum lncRNAGAS5 and LncRNABISPR were upregulated,whereas mRNA BST2 and LncRNA HEIH were downregulated in naïve patients.In contrast,HCV patients treated with sofosbuvir and simeprevir;with sofosbuvir and daclatasvir;or with sofosbuvir,daclatasvir and ribavirin exhibited lower levels of lncRNAGAS5 and lncRNABISPR with higher mRNABST2 compared to naïve patients.Notably,patients relapsed from sofosbuvir and simeprevir showed higher levels of these lncRNAs with lower mRNABST2 compared to treated patients.LncRNAGAS5 and lncRNABISPR were positively correlated with viral load and ALT at P<0.001,whereas mRNABST2 was negatively correlated with viral load at P<0.001 and ALT at P<0.05.Interestingly,a significant positive correlation between lncRNA HEIH and AFP was observed at P<0.001.CONCLUSION Differential expression of these RNAs suggests their involvement in HCV pathogenesis or antiviral response and highlights their promising roles in diagnosis and prognosis of HCV.
