参考黑线仓鼠(Cricetulus barabensis)近缘种PPARβ的cDNA序列设计引物,采用RT-PCR法克隆得到黑线仓鼠PPARβ部分序列,并翻译成氨基酸.利用该结果与其他物种核苷酸及氨基酸序列进行相似性比较、构建系统进化树、一级结构分析、二级结构...参考黑线仓鼠(Cricetulus barabensis)近缘种PPARβ的cDNA序列设计引物,采用RT-PCR法克隆得到黑线仓鼠PPARβ部分序列,并翻译成氨基酸.利用该结果与其他物种核苷酸及氨基酸序列进行相似性比较、构建系统进化树、一级结构分析、二级结构和空间结构预测.结果表明:得到的480 bp PPARβ序列包括部分外显子4,全部外显子5、6及部分外显子7;共编码159个氨基酸;除人之外,黑线仓鼠PPARβ基因与其他物种的核苷酸相似性均在88%-94%之间,氨基酸相似性均在90%以上;构建进化树得出,黑线仓鼠与鼠类亲缘关系最近,与人的亲缘关系最远;疏水性分析、二级结构预显示该编码区亲水性较强;二级结构、空间结构预测显示该序列含α螺旋较多;空间结构预测看出该段区域含两个典型的锌指结构.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions.Nuclear receptor agonists ha...Metabolic dysfunction-associated steatotic liver disease(MASLD)is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions.Nuclear receptor agonists have been under scrutiny as potential pharmacological targets and as of today,resmetirom,a thyroid hormone receptor b agonist,is the only approved agent.The dual PPARαandδagonist elafibranor has also undergone extensive clinical testing,which reached the phase III clinical trial but failed to demonstrate a beneficial effect on MASLD.As alcohol-associated liver disease and MASLD can be interconnected,whether elafibranor might be affective against liver disease caused by alcohol consumption is worth investigating.Writing recently in the World Journal of Gastroenterology,Koizumi et al reported using a mouse model of alcoholassociated liver disease and found that hepatic steatosis,liver fibrosis,and hepatocyte apoptosis were alleviated by administration of elafibranor.Although preclinical in nature,these data support the potential beneficial action of elafibranor in alcohol-induced MASLD,warranting the testing of this molecule in patients with steatotic liver disease caused by alcohol consumption.展开更多
Objective:To investigate the effects of Alpiniae oxyphyllae Fructus(AOF)on renal lipid deposition in diabetic kidney disease(DKD)and elucidate its molecular mechanisms.Methods:The mechanism of AOF in treating DKD was ...Objective:To investigate the effects of Alpiniae oxyphyllae Fructus(AOF)on renal lipid deposition in diabetic kidney disease(DKD)and elucidate its molecular mechanisms.Methods:The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation.The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells.Cell viability and lipid accumulation were detected by CCK8 and oil red O staining.The expressions of PPARαand fatty acid oxidation-related genes(ACOX1 and CPT1A)were detected by quantitative RT-PCR,Western blot,and immunofluorescence.Furthermore,PPARαknockdown was performed to examine the molecular mechanism of AOF in treating DKD.Results:Network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation showed that the active compounds in AOF targeted PPARαand thus transcriptionally regulated ACOX1 and CPT1A.AOF lowered blood glucose,improved dyslipidemia,and attenuated renal injury in DKD mice.AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation.Additionally,it significantly upregulated the expression of PPARα,ACOX1,and CPT1A in both in vivo and in vitro experiments,which was reversed by PPARαknockdown.Conclusions:AOF may promote fatty acid oxidation via PPARαto ameliorate renal lipid deposition in DKD.展开更多
文摘参考黑线仓鼠(Cricetulus barabensis)近缘种PPARβ的cDNA序列设计引物,采用RT-PCR法克隆得到黑线仓鼠PPARβ部分序列,并翻译成氨基酸.利用该结果与其他物种核苷酸及氨基酸序列进行相似性比较、构建系统进化树、一级结构分析、二级结构和空间结构预测.结果表明:得到的480 bp PPARβ序列包括部分外显子4,全部外显子5、6及部分外显子7;共编码159个氨基酸;除人之外,黑线仓鼠PPARβ基因与其他物种的核苷酸相似性均在88%-94%之间,氨基酸相似性均在90%以上;构建进化树得出,黑线仓鼠与鼠类亲缘关系最近,与人的亲缘关系最远;疏水性分析、二级结构预显示该编码区亲水性较强;二级结构、空间结构预测显示该序列含α螺旋较多;空间结构预测看出该段区域含两个典型的锌指结构.
文摘过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPAR)是核激素受体家族中的配体激活的转录因子,有PPARα、PPARβ/δ及PPARγ3种亚型,其中PPARβ/δ控制许多细胞内的代谢过程,包括长链脂肪酸、胆固醇和鞘脂的代谢等。PPARβ/δ作为一种转录因子,易被膳食脂质和内源性配体(如长链饱和脂肪酸和多不饱和脂肪酸)以及某些脂质代谢产物激活,通过与视黄醇X受体α(retinoid X receptorα,RXRα)的相互作用显示转录活性,显著调节糖、脂代谢、线粒体功能和细胞发育。尽管它在脑细胞及大脑的不同区域中含量较丰富,但关于其在神经退化以及神经炎症中的作用仍知之甚少。近年来PPARβ/δ在神经退行性疾病中的作用及其调控机制日益受到人们的关注,该文对PPARβ/δ的结构、功能以及其在阿尔茨海默病、帕金森病、亨廷顿病以及多发性硬化症等神经退行性疾病中的作用进行综述。
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions.Nuclear receptor agonists have been under scrutiny as potential pharmacological targets and as of today,resmetirom,a thyroid hormone receptor b agonist,is the only approved agent.The dual PPARαandδagonist elafibranor has also undergone extensive clinical testing,which reached the phase III clinical trial but failed to demonstrate a beneficial effect on MASLD.As alcohol-associated liver disease and MASLD can be interconnected,whether elafibranor might be affective against liver disease caused by alcohol consumption is worth investigating.Writing recently in the World Journal of Gastroenterology,Koizumi et al reported using a mouse model of alcoholassociated liver disease and found that hepatic steatosis,liver fibrosis,and hepatocyte apoptosis were alleviated by administration of elafibranor.Although preclinical in nature,these data support the potential beneficial action of elafibranor in alcohol-induced MASLD,warranting the testing of this molecule in patients with steatotic liver disease caused by alcohol consumption.
基金This work was supported by the grants from National Natural Science Foundation of China(No.82174334)2022 Postgraduate Innovation Research Projects in Hainan Province(No.Qhys2022-273).
文摘Objective:To investigate the effects of Alpiniae oxyphyllae Fructus(AOF)on renal lipid deposition in diabetic kidney disease(DKD)and elucidate its molecular mechanisms.Methods:The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation.The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells.Cell viability and lipid accumulation were detected by CCK8 and oil red O staining.The expressions of PPARαand fatty acid oxidation-related genes(ACOX1 and CPT1A)were detected by quantitative RT-PCR,Western blot,and immunofluorescence.Furthermore,PPARαknockdown was performed to examine the molecular mechanism of AOF in treating DKD.Results:Network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation showed that the active compounds in AOF targeted PPARαand thus transcriptionally regulated ACOX1 and CPT1A.AOF lowered blood glucose,improved dyslipidemia,and attenuated renal injury in DKD mice.AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation.Additionally,it significantly upregulated the expression of PPARα,ACOX1,and CPT1A in both in vivo and in vitro experiments,which was reversed by PPARαknockdown.Conclusions:AOF may promote fatty acid oxidation via PPARαto ameliorate renal lipid deposition in DKD.
