Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which choleste...Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which cholesterol is esterified to be transported to target organs. The newly developed process of making bulky esters from unprecedented tertiary alcohols is applied to synthesize cholesterol esters successfully. Although cholesterol is a secondary alcohol, it is a very bulky and interesting compound due to its immense application. Usually, specific enzymes catalyze cholesterol to cholesterol ester. This project aims to develop a cross-coupling chemistry process to synthesize cholesterol esters and see the broader application of those new cholesterol esters in chemical biology. The mixture of cholesterol, sodium tert-butoxide, aroyl chloride, the catalyst PdCl2 (dtbpf) complex, and the solvent 1,4-dioxane, when microwaved at 100˚C for 2 hours, works well for the formation of cross-coupling cholesterol ester products in good to high yields.展开更多
A series ofpenicillide analogues, with modifications at C-3 and C-9 positions, are synthesized as potential cho-lesteryl ester transfer protein （CETP） inhibitors. The preliminary in vitro inhibition assay provided s...A series ofpenicillide analogues, with modifications at C-3 and C-9 positions, are synthesized as potential cho-lesteryl ester transfer protein （CETP） inhibitors. The preliminary in vitro inhibition assay provided some valuable structure-activity relationship information about penicillide.展开更多
By using an LKB-2277 Bioactivity Monitor, the effect ofporphyrin-cholesterol esters on cancer cells RL-60 were examined at 25℃.There is a dirrerence in the shape of the thermogenesls curve samong different kinds or ...By using an LKB-2277 Bioactivity Monitor, the effect ofporphyrin-cholesterol esters on cancer cells RL-60 were examined at 25℃.There is a dirrerence in the shape of the thermogenesls curve samong different kinds or Porphyrln-cholesterol esters,and the death rate or HL-60 cells is also different. The results show that porphyrin-chsterol esters can powerfully inhibit their metabolism, the inhibitory sequence is Ⅱ >I >Ⅲ,but the inhibitory way of each ester is different.展开更多
目的评估磷脂酰乙醇胺(phosphatidylethanolamine,PE)与前列腺癌风险的因果关联,并探讨超大粒径高密度脂蛋白中的胆固醇酯(cholesterol esters in very large HDL,XL.HDL.CE)是否在其中发挥中介作用。方法使用公开的全基因组关联研究(GW...目的评估磷脂酰乙醇胺(phosphatidylethanolamine,PE)与前列腺癌风险的因果关联,并探讨超大粒径高密度脂蛋白中的胆固醇酯(cholesterol esters in very large HDL,XL.HDL.CE)是否在其中发挥中介作用。方法使用公开的全基因组关联研究(GWAS)数据,使用双样本孟德尔随机化(Mendelian randomization,MR)方法,评估PE水平与前列腺癌之间的因果关系。使用随机效应模型下的逆方差加权法作为主要分析手段,以MR-Egger回归、加权中位数法、简单模式法和加权模式法作为辅助对结果进行一致性验证。同时,通过Cochran’s Q统计量、MR-Egger截距检验、MR-PRESSO及Leave-one-out分析评估分析结果的稳健性。采用反向MR分析,将前列腺癌作为暴露因素,PE水平作为结局变量探索反向因果关系的可能。采用两步式MR方法评估XL.HDL.CE的中介效应。结果逆方差加权法分析显示,PE水平升高与前列腺癌发生风险显著正相关(OR=1.084,95%CI:1.038-1.133,P=0.000252)。辅助分析结果显示方向一致且大部分具有统计学意义。敏感性分析未发现显著的异质性或多效性干扰,进一步支持结果的稳健性。反向MR分析结果未达到显著性水平,排除反向因果关系的可能。中介分析显示,XL.HDL.CE在PE影响前列腺癌风险中发挥显著中介作用(间接效应β=0.0397,P=0.0020),中介比例为49%。结论PE水平升高与前列腺癌发生风险显著正相关,XL.HDL.CE在其中可能发挥关键的中介作用。提示脂质代谢通路在前列腺癌发病过程中可能具有重要生物学意义,为疾病的预防和治疗提供了新思路。展开更多
目的:建立检测胆固醇酯转运蛋白(cholesterol ester transfer protein,CETP)基因6种常见突变的等位基因特异性PCR技术。方法:应用针对CETP基因TaqIB(G→A)、I405V(A→G)、D442G(A→G)、R451Q(G→A)、A373P(G→C)和I14A(G→A)这6种常见...目的:建立检测胆固醇酯转运蛋白(cholesterol ester transfer protein,CETP)基因6种常见突变的等位基因特异性PCR技术。方法:应用针对CETP基因TaqIB(G→A)、I405V(A→G)、D442G(A→G)、R451Q(G→A)、A373P(G→C)和I14A(G→A)这6种常见的突变位点设计的等位基因特异性PCR技术,对海南汉、黎族人群中CETP基因突变类型进行了检测,同时对经上述等位基因特异性PCR检测的样本进行序列测定。结果:在海南汉、黎族人群中,TaqIB(G→A)突变位点可检测出GG、GA、AA3种基因型,I405V(A→G)突变位点可检测出AA、AG、GG3种基因型,D442G(A→G)突变位点可检测出AA、AG2种基因型,但在海南汉、黎族人群中未检测到R451Q(G→A)、A373P(G→C)和I14A(G→A)3种突变类型,用等位基因特异性PCR鉴定的CETP基因突变的基因分型结果与序列测定结果完全符合。结论:等位基因特异性PCR技术操作简便,重复性和稳定性好,可作为鉴定CETP基因突变类型的可行方法。展开更多
目的利用液相色谱-质谱联用法测定细胞内胆固醇及胆固醇酯,建立一种精确鉴定泡沫细胞的方法。方法用氧化修饰低密度脂蛋白(oxidized low density lipoprotein,oxLDL)干预U937巨噬细胞诱导泡沫细胞形成,然后用己烷/异丙醇(体积比3/2)抽...目的利用液相色谱-质谱联用法测定细胞内胆固醇及胆固醇酯,建立一种精确鉴定泡沫细胞的方法。方法用氧化修饰低密度脂蛋白(oxidized low density lipoprotein,oxLDL)干预U937巨噬细胞诱导泡沫细胞形成,然后用己烷/异丙醇(体积比3/2)抽提细胞内胆固醇及胆固醇酯,抽提液经真空干燥后再溶于甲醇,用液相色谱-质谱联用法直接测定细胞内游离胆固醇,胆固醇酯经胆固醇酯酶水解后测定总胆固醇,总胆固醇减去游离胆固醇即胆固醇酯。抽提脂质后的沉淀物溶于氢氧化钠溶液中,用BCA法测定蛋白含量,胆固醇及胆固醇酯用μg/mg细胞蛋白为单位来表示。结果氧化低密度脂蛋白干预后的巨噬细胞内存在高水平胆固醇及胆固醇酯的蓄积。在100μg的oxLDL处理组中,胆固醇酯与阴性对照组差异存在显著性[(25.733±2.970)μg/mg细胞蛋白vs (13.024±2.875)μg/mg细胞蛋白,P<0.01],同样胆固醇的水平差异也存在显著性[(18.675±1.315)μg/mg细胞蛋白vs (24.428±2.370)μg/mg细胞蛋白,P<0.01]。结论液相色谱-质谱联用法测定细胞内胆固醇是一种鉴定泡沫细胞简便而精确的方法。展开更多
文摘Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which cholesterol is esterified to be transported to target organs. The newly developed process of making bulky esters from unprecedented tertiary alcohols is applied to synthesize cholesterol esters successfully. Although cholesterol is a secondary alcohol, it is a very bulky and interesting compound due to its immense application. Usually, specific enzymes catalyze cholesterol to cholesterol ester. This project aims to develop a cross-coupling chemistry process to synthesize cholesterol esters and see the broader application of those new cholesterol esters in chemical biology. The mixture of cholesterol, sodium tert-butoxide, aroyl chloride, the catalyst PdCl2 (dtbpf) complex, and the solvent 1,4-dioxane, when microwaved at 100˚C for 2 hours, works well for the formation of cross-coupling cholesterol ester products in good to high yields.
基金We thank the National Natural Science Foundation of China （20872019） for the research financial support and we are grateful to Fudan University and Shanghai Institute of Organic Chemistry for recording EI-MS or ESI-MS, HRMS, ^1H NMR, and ^13C NMR spectra. We are also grateful to Dr. Hanqing Dong （OSI Pharma-ceuticals, USA） for his help in revising the manuscript.
文摘A series ofpenicillide analogues, with modifications at C-3 and C-9 positions, are synthesized as potential cho-lesteryl ester transfer protein （CETP） inhibitors. The preliminary in vitro inhibition assay provided some valuable structure-activity relationship information about penicillide.
文摘By using an LKB-2277 Bioactivity Monitor, the effect ofporphyrin-cholesterol esters on cancer cells RL-60 were examined at 25℃.There is a dirrerence in the shape of the thermogenesls curve samong different kinds or Porphyrln-cholesterol esters,and the death rate or HL-60 cells is also different. The results show that porphyrin-chsterol esters can powerfully inhibit their metabolism, the inhibitory sequence is Ⅱ >I >Ⅲ,but the inhibitory way of each ester is different.
文摘目的评估磷脂酰乙醇胺(phosphatidylethanolamine,PE)与前列腺癌风险的因果关联,并探讨超大粒径高密度脂蛋白中的胆固醇酯(cholesterol esters in very large HDL,XL.HDL.CE)是否在其中发挥中介作用。方法使用公开的全基因组关联研究(GWAS)数据,使用双样本孟德尔随机化(Mendelian randomization,MR)方法,评估PE水平与前列腺癌之间的因果关系。使用随机效应模型下的逆方差加权法作为主要分析手段,以MR-Egger回归、加权中位数法、简单模式法和加权模式法作为辅助对结果进行一致性验证。同时,通过Cochran’s Q统计量、MR-Egger截距检验、MR-PRESSO及Leave-one-out分析评估分析结果的稳健性。采用反向MR分析,将前列腺癌作为暴露因素,PE水平作为结局变量探索反向因果关系的可能。采用两步式MR方法评估XL.HDL.CE的中介效应。结果逆方差加权法分析显示,PE水平升高与前列腺癌发生风险显著正相关(OR=1.084,95%CI:1.038-1.133,P=0.000252)。辅助分析结果显示方向一致且大部分具有统计学意义。敏感性分析未发现显著的异质性或多效性干扰,进一步支持结果的稳健性。反向MR分析结果未达到显著性水平,排除反向因果关系的可能。中介分析显示,XL.HDL.CE在PE影响前列腺癌风险中发挥显著中介作用(间接效应β=0.0397,P=0.0020),中介比例为49%。结论PE水平升高与前列腺癌发生风险显著正相关,XL.HDL.CE在其中可能发挥关键的中介作用。提示脂质代谢通路在前列腺癌发病过程中可能具有重要生物学意义,为疾病的预防和治疗提供了新思路。
文摘目的:建立检测胆固醇酯转运蛋白(cholesterol ester transfer protein,CETP)基因6种常见突变的等位基因特异性PCR技术。方法:应用针对CETP基因TaqIB(G→A)、I405V(A→G)、D442G(A→G)、R451Q(G→A)、A373P(G→C)和I14A(G→A)这6种常见的突变位点设计的等位基因特异性PCR技术,对海南汉、黎族人群中CETP基因突变类型进行了检测,同时对经上述等位基因特异性PCR检测的样本进行序列测定。结果:在海南汉、黎族人群中,TaqIB(G→A)突变位点可检测出GG、GA、AA3种基因型,I405V(A→G)突变位点可检测出AA、AG、GG3种基因型,D442G(A→G)突变位点可检测出AA、AG2种基因型,但在海南汉、黎族人群中未检测到R451Q(G→A)、A373P(G→C)和I14A(G→A)3种突变类型,用等位基因特异性PCR鉴定的CETP基因突变的基因分型结果与序列测定结果完全符合。结论:等位基因特异性PCR技术操作简便,重复性和稳定性好,可作为鉴定CETP基因突变类型的可行方法。
