The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to th...The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.展开更多
目的研究血清前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)和几丁质酶-3样蛋白1(chitinase-3-like protein 1,CHI3L1)水平与脑血管病所致认知功能障碍的相关性。方法选取2020年10月~2022年10月成都市第三人...目的研究血清前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)和几丁质酶-3样蛋白1(chitinase-3-like protein 1,CHI3L1)水平与脑血管病所致认知功能障碍的相关性。方法选取2020年10月~2022年10月成都市第三人民医院收治的96例脑血管病住院患者为研究对象。记录患者基本临床资料,酶联免疫吸附法(ELISA)检测血清PTGS2和CHI3L1水平,患者依据有无认知功能障碍分为正常组(n=60)和障碍组(n=36);血清PTGS2和CHI3L1水平与空腹血糖(fasting blood glucose,FBG)、同型半胱氨酸(homocysteine,Hcy)的相关性采用Pearson法分析;Logistic回归模型判断血清PTGS2和CHI3L1是否可作为预测认知功能障碍的独立危险因素;绘制受试者工作特征(receiver operating characteristic,ROC)曲线,根据曲线下面积(area under the curve,AUC)分析血清PTGS2和CHI3L1表达水平对脑血管病患者认知功能障碍的预测价值。结果与正常组比较,障碍组血清PTGS2(29.30±9.46 pg/ml vs 17.86±5.40 pg/ml),CHI3L1(13.04±4.06 pg/ml vs 7.51±2.66 pg/ml)水平均升高,差异有统计学意义(t=7.553,8.065,均P<0.05);多因素Logistic回归分析结果显示,FBG(OR=3.612,95%CI:2.324~5.614),Hcy(OR=2.584,95%CI:1.351~4.944),PTGS2(OR=1.964,95%CI:1.194~3.231)和CHI3L1(OR=1.556,95%CI:1.023~2.367)是认知功能障碍的独立危险因素(均P<0.05);PTGS2与FBG,Hcy呈正相关(r=0.368,0.551,均P<0.05),CHI3L1与FBG,Hcy呈正相关(r=0.510,0.376,均P<0.05)。ROC曲线显示,PTGS2预测认知功能障碍的AUC为0.819,CHI3L1预测认知功能障碍的AUC为0.829,二者联合预测认知功能障碍的AUC为0.902,高于二者单独预测(Z=2.089,2.293;P=0.037,0.021),其敏感度和特异度分别为77.78%,98.33%。结论PTGS2和CHI3L1在脑血管病认知功能障碍患者血清中高表达,二者均与脑血管病患者认知功能障碍有关。展开更多
基金Supported by Ministerio de Ciencia Innovación y Universidades,No.SAF2017-82436R and SAF2016-75004RComunidad de Madrid,No.S2017/BMD-3686+2 种基金Fundación Ramón Areces,No.2016/CIVP18A3864Instituto de Salud Carlos Ⅲby Fondos FEDER,No.Cibercv and Ciberehd
文摘The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.
文摘目的研究血清前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)和几丁质酶-3样蛋白1(chitinase-3-like protein 1,CHI3L1)水平与脑血管病所致认知功能障碍的相关性。方法选取2020年10月~2022年10月成都市第三人民医院收治的96例脑血管病住院患者为研究对象。记录患者基本临床资料,酶联免疫吸附法(ELISA)检测血清PTGS2和CHI3L1水平,患者依据有无认知功能障碍分为正常组(n=60)和障碍组(n=36);血清PTGS2和CHI3L1水平与空腹血糖(fasting blood glucose,FBG)、同型半胱氨酸(homocysteine,Hcy)的相关性采用Pearson法分析;Logistic回归模型判断血清PTGS2和CHI3L1是否可作为预测认知功能障碍的独立危险因素;绘制受试者工作特征(receiver operating characteristic,ROC)曲线,根据曲线下面积(area under the curve,AUC)分析血清PTGS2和CHI3L1表达水平对脑血管病患者认知功能障碍的预测价值。结果与正常组比较,障碍组血清PTGS2(29.30±9.46 pg/ml vs 17.86±5.40 pg/ml),CHI3L1(13.04±4.06 pg/ml vs 7.51±2.66 pg/ml)水平均升高,差异有统计学意义(t=7.553,8.065,均P<0.05);多因素Logistic回归分析结果显示,FBG(OR=3.612,95%CI:2.324~5.614),Hcy(OR=2.584,95%CI:1.351~4.944),PTGS2(OR=1.964,95%CI:1.194~3.231)和CHI3L1(OR=1.556,95%CI:1.023~2.367)是认知功能障碍的独立危险因素(均P<0.05);PTGS2与FBG,Hcy呈正相关(r=0.368,0.551,均P<0.05),CHI3L1与FBG,Hcy呈正相关(r=0.510,0.376,均P<0.05)。ROC曲线显示,PTGS2预测认知功能障碍的AUC为0.819,CHI3L1预测认知功能障碍的AUC为0.829,二者联合预测认知功能障碍的AUC为0.902,高于二者单独预测(Z=2.089,2.293;P=0.037,0.021),其敏感度和特异度分别为77.78%,98.33%。结论PTGS2和CHI3L1在脑血管病认知功能障碍患者血清中高表达,二者均与脑血管病患者认知功能障碍有关。
