Clear cell renal cell carcinoma(KIRC)is the most common and aggressivemalignancy subtype of renal neoplasm that arises from proximal convoluted tubules.It is characterized by poor clinical outcomes and high mortality ...Clear cell renal cell carcinoma(KIRC)is the most common and aggressivemalignancy subtype of renal neoplasm that arises from proximal convoluted tubules.It is characterized by poor clinical outcomes and high mortality of patients due to the lack of specific biomarkers for varying stages of the disease and no effective treatment.Proteases are associated with the development of several malignant tumors in humans by their ability to degrade extracellular matrices,facilitating metastasis.Herein,differentially expressed genes in KIRC cases compared to healthy kidneys were screened out from the Gene Expression Profiling Interactive Analysis(GEPIA)database.This data was applied to determine the most elevated protease in KIRC and as a result,A Disintegrin and Metalloproteinase Domain-Like Protein Decysin-1(ADAMDEC1)was selected.This expression pattern was exclusive for KIRC and not observed for papillary and chromophobe renal cell carcinomas,in which ADAMDEC1 was at the same level in tumors and non-cancer specimens.Furthermore,the ADAMDEC1 significant increase was detected in the fourteen other human malignancies compared to healthy samples,which suggested its strong involvement in cancer development.Next,GEPIA and Pathology Atlas correlated ADAMDEC1 high expression with more advanced tumor grade and shorter survival of KIRC patients.Xena Functional Genomics Explorer presented that ADAMDEC1 could be hypermethylated in some tumor cases and one somatic mutation in the gene sequence was detected.Finally,a Search Tool for the Retrieval of Interacting Genes/Proteins;STRING base was utilized to predict the interactions of ADAMDEC1 with other molecules and construct the signaling network.In summary,ADAMDEC1 showed the tremendous potential to be the predictive marker for the KIRC and its development.Therefore,this review with data analysis can be a good base for further in vitro and in vivo research that experimentally can confirm the ADAMDEC1 as prognostic biomarkers and therapeutic target of KIRC.展开更多
目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与...目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与其心血管功能及预后的关系。方法选取大庆市人民医院2020年6月至2022年6月收治的132例高血压患者作为观察对象,根据同型半胱氨酸(homocysteine,Hcy)浓度分为非H型高血压组40例和H型高血压组92例,根据预后情况将H型高血压患者分为预后良好组和预后不良组,并选择同期来大庆市人民医院健康体检的成年人70名作为对照组。采用酶联免疫吸附试验法检测受试者血清中DcR3、ADAMTS13浓度,Pearson法分析血清中DcR3、ADAMTS13浓度与心血管功能指标的相关性,多因素Logistic回归分析H型高血压患者1年预后不良的影响因素。绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清DcR3、ADAMTS13浓度对H型高血压患者1年预后不良的预测价值。结果与对照组[(122.28±32.34)mmHg(1 mmHg=0.133 kPa)、(48.16±8.65)mmHg、(8.59±1.25)mm、(118.34±34.25)g/m2、(1.48±0.34)g/L、(57.15±14.94)mg/L、(1.45±0.31)、70.28%±15.21%]比较,H型高血压组患者的收缩压[(139.35±38.21)mmHg]、脉压[(57.37±11.75)mmHg]、左心室后壁厚度(posterior wall thickness,PWT)[(11.69±2.00)mm]以及左心室质量指数(left ventricular mass index,LVMI)[(148.54±38.22)g/m2]显著升高,DcR3[(0.74±0.19)g/L]、ADAMTS13浓度[(14.13±4.62)mg/L]、二尖瓣舒张早期血流峰值/二尖瓣舒张晚期血流峰值(E-peak to A-peak of the mitral flow spectrum,E/A)(0.65±0.13)、左心室射血分数(left ventricular ejection fraction,LVEF)(64.26%±12.75%)显著降低,差异有统计学意义(P<0.05);与非H型高血压组患者组比较,H型高血压组患者的DcR3、ADAMTS13浓度及E/A显著降低,LVMI显著升高,差异有统计学意义(P<0.05)。H型高血压组患者血清中DcR3、ADAMTS13浓度均与收缩压、脉压和LVMI呈负相关(P<0.05),而与E/A、LVEF呈正相关(P<0.05)。预后不良组患者的年龄显著高于预后良好组,E/A(0.38±0.07)、DcR3[(0.45±0.13)g/L]、ADAMTS13浓度[(8.45±2.11)mg/L]显著低于预后良好组[0.75±0.11、(0.85±0.27)g/L、(16.25±4.85)mg/L],差异有统计学意义(P<0.05)。DcR3、ADAMTS13是H型高血压患者预后不良的保护因素(P<0.05)。血清DcR3、ADAMTS13浓度单独及二者联合预测H型高血压患者1年发生预后不良的曲线下面积(area under the curve,AUC)分别为0.906、0.844、0.950。结论H型高血压疾病患者血清DcR3、ADAMTS13浓度降低,与心血管功能及预后密切相关,对该疾病的预后评估有重要价值。展开更多
A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) specifically cleaves unusually-large von Willebrand factor(VWF) multimers under high shear stress,and down-regulates VWF function...A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) specifically cleaves unusually-large von Willebrand factor(VWF) multimers under high shear stress,and down-regulates VWF function to form platelet thrombi.Deficiency of plasma ADAMTS13 activity induces a life-threatening systemic disease,termed thrombotic microangiopathy(TMA) including thrombotic thrombocytopenic purpura(TTP).Children with advanced biliary cirrhosis due to congenital biliary atresia sometimes showed pathological features of TMA,with a concomitant decrease of plasma ADAMTS13 activity.Disappearance of their clinical findings of TTP after successful liver transplantation suggested that the liver is a major organ producing plasma ADAMTS13.In situ hybridization analysis showed that ADAMTS13 was produced by hepatic stellate cells.Subsequently,it was found that ADADTS13 was not merely responsible to development of TMA and TTP,but also related to some kinds of liver dysfunction after liver transplantation.Ischemia-reperfusion injury and acute rejection in liver transplant recipients were often associated with marked decrease of ADAMTS13 and concomitant formation of unusually large VWF multimers without findings of TMA/TTP.The similar phenomenon was observed also in patients who underwent hepatectomy for liver tumors.Imbalance between ADAMTS13 and VWF in the hepatic sinusoid might cause liver damage due to microcirculatory disturbance.It can be called as "local TTP like mechanism" which plays a crucial role in liver dysfunction after liver transplantation and surgery.展开更多
目的:检测大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期海马组织中含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin-like and metalloproteinase with thrombospondin type l motifs,ADAMTS-1)在基底动脉...目的:检测大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期海马组织中含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin-like and metalloproteinase with thrombospondin type l motifs,ADAMTS-1)在基底动脉中的表达,分析其与大鼠SAH后急性脑血管痉挛(cerebral vasospasm,CVS)的相关性,探讨其在SAH后早期脑损伤(earlybrain injury,EBI)中的作用。方法:健康雄性成年SD大鼠108只,体质量250～300g,随机分为SAH组(n=90)和假手术组(sham组,n=18)。SAH组取大鼠自体动脉血,用视交叉池注血法建立大鼠SAH模型(sham组注入等量0.9%氯化钠液)。将SAH组随机分为6h、12h、24h、48h、72h5个亚组,每个亚组18只,分别在相应时间点处死。用蛋白质印迹(Western-blot)方法及实时荧光定量逆转录-聚合酶链反应(RT-PCR)法检测SAH各亚组及sham组基底动脉ADAMTS-1的表达,同时用HE染色法对基底动脉进行形态学观察。探讨ADAMTS-1与实验性大鼠SAH后急性CVS的相关性。结果:与sham组相比,SAH 6h亚组基底动脉ADAMTS-1表达无显著差异;12h亚组基底动脉ADAMTS-1蛋白表达显著增高,24h亚组最高,48h亚组、72h亚组逐渐下降,但仍维持在较高水平。与sham组相比,SAH 6h亚组大鼠基底动脉变化不明显;12h亚组大鼠基底动脉管腔缩小,管壁增厚;24h亚组基底动脉痉挛最为明显;48h亚组基底动脉痉挛较24h亚组减轻;与24h亚组、48h亚组相比,72h亚组基底动脉管腔直径更大、管壁厚度更薄。ADAMTS-1蛋白表达与SAH后急性CVS呈正相关(r=0.916,P=0.003)。结论:大鼠SAH后早期基底动脉ADAMTS-1表达与急性CVS正相关,提示ADAMTS-1可能参与大鼠SAH后EBI的病理过程。展开更多
文摘Clear cell renal cell carcinoma(KIRC)is the most common and aggressivemalignancy subtype of renal neoplasm that arises from proximal convoluted tubules.It is characterized by poor clinical outcomes and high mortality of patients due to the lack of specific biomarkers for varying stages of the disease and no effective treatment.Proteases are associated with the development of several malignant tumors in humans by their ability to degrade extracellular matrices,facilitating metastasis.Herein,differentially expressed genes in KIRC cases compared to healthy kidneys were screened out from the Gene Expression Profiling Interactive Analysis(GEPIA)database.This data was applied to determine the most elevated protease in KIRC and as a result,A Disintegrin and Metalloproteinase Domain-Like Protein Decysin-1(ADAMDEC1)was selected.This expression pattern was exclusive for KIRC and not observed for papillary and chromophobe renal cell carcinomas,in which ADAMDEC1 was at the same level in tumors and non-cancer specimens.Furthermore,the ADAMDEC1 significant increase was detected in the fourteen other human malignancies compared to healthy samples,which suggested its strong involvement in cancer development.Next,GEPIA and Pathology Atlas correlated ADAMDEC1 high expression with more advanced tumor grade and shorter survival of KIRC patients.Xena Functional Genomics Explorer presented that ADAMDEC1 could be hypermethylated in some tumor cases and one somatic mutation in the gene sequence was detected.Finally,a Search Tool for the Retrieval of Interacting Genes/Proteins;STRING base was utilized to predict the interactions of ADAMDEC1 with other molecules and construct the signaling network.In summary,ADAMDEC1 showed the tremendous potential to be the predictive marker for the KIRC and its development.Therefore,this review with data analysis can be a good base for further in vitro and in vivo research that experimentally can confirm the ADAMDEC1 as prognostic biomarkers and therapeutic target of KIRC.
文摘目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与其心血管功能及预后的关系。方法选取大庆市人民医院2020年6月至2022年6月收治的132例高血压患者作为观察对象,根据同型半胱氨酸(homocysteine,Hcy)浓度分为非H型高血压组40例和H型高血压组92例,根据预后情况将H型高血压患者分为预后良好组和预后不良组,并选择同期来大庆市人民医院健康体检的成年人70名作为对照组。采用酶联免疫吸附试验法检测受试者血清中DcR3、ADAMTS13浓度,Pearson法分析血清中DcR3、ADAMTS13浓度与心血管功能指标的相关性,多因素Logistic回归分析H型高血压患者1年预后不良的影响因素。绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清DcR3、ADAMTS13浓度对H型高血压患者1年预后不良的预测价值。结果与对照组[(122.28±32.34)mmHg(1 mmHg=0.133 kPa)、(48.16±8.65)mmHg、(8.59±1.25)mm、(118.34±34.25)g/m2、(1.48±0.34)g/L、(57.15±14.94)mg/L、(1.45±0.31)、70.28%±15.21%]比较,H型高血压组患者的收缩压[(139.35±38.21)mmHg]、脉压[(57.37±11.75)mmHg]、左心室后壁厚度(posterior wall thickness,PWT)[(11.69±2.00)mm]以及左心室质量指数(left ventricular mass index,LVMI)[(148.54±38.22)g/m2]显著升高,DcR3[(0.74±0.19)g/L]、ADAMTS13浓度[(14.13±4.62)mg/L]、二尖瓣舒张早期血流峰值/二尖瓣舒张晚期血流峰值(E-peak to A-peak of the mitral flow spectrum,E/A)(0.65±0.13)、左心室射血分数(left ventricular ejection fraction,LVEF)(64.26%±12.75%)显著降低,差异有统计学意义(P<0.05);与非H型高血压组患者组比较,H型高血压组患者的DcR3、ADAMTS13浓度及E/A显著降低,LVMI显著升高,差异有统计学意义(P<0.05)。H型高血压组患者血清中DcR3、ADAMTS13浓度均与收缩压、脉压和LVMI呈负相关(P<0.05),而与E/A、LVEF呈正相关(P<0.05)。预后不良组患者的年龄显著高于预后良好组,E/A(0.38±0.07)、DcR3[(0.45±0.13)g/L]、ADAMTS13浓度[(8.45±2.11)mg/L]显著低于预后良好组[0.75±0.11、(0.85±0.27)g/L、(16.25±4.85)mg/L],差异有统计学意义(P<0.05)。DcR3、ADAMTS13是H型高血压患者预后不良的保护因素(P<0.05)。血清DcR3、ADAMTS13浓度单独及二者联合预测H型高血压患者1年发生预后不良的曲线下面积(area under the curve,AUC)分别为0.906、0.844、0.950。结论H型高血压疾病患者血清DcR3、ADAMTS13浓度降低,与心血管功能及预后密切相关,对该疾病的预后评估有重要价值。
文摘A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) specifically cleaves unusually-large von Willebrand factor(VWF) multimers under high shear stress,and down-regulates VWF function to form platelet thrombi.Deficiency of plasma ADAMTS13 activity induces a life-threatening systemic disease,termed thrombotic microangiopathy(TMA) including thrombotic thrombocytopenic purpura(TTP).Children with advanced biliary cirrhosis due to congenital biliary atresia sometimes showed pathological features of TMA,with a concomitant decrease of plasma ADAMTS13 activity.Disappearance of their clinical findings of TTP after successful liver transplantation suggested that the liver is a major organ producing plasma ADAMTS13.In situ hybridization analysis showed that ADAMTS13 was produced by hepatic stellate cells.Subsequently,it was found that ADADTS13 was not merely responsible to development of TMA and TTP,but also related to some kinds of liver dysfunction after liver transplantation.Ischemia-reperfusion injury and acute rejection in liver transplant recipients were often associated with marked decrease of ADAMTS13 and concomitant formation of unusually large VWF multimers without findings of TMA/TTP.The similar phenomenon was observed also in patients who underwent hepatectomy for liver tumors.Imbalance between ADAMTS13 and VWF in the hepatic sinusoid might cause liver damage due to microcirculatory disturbance.It can be called as "local TTP like mechanism" which plays a crucial role in liver dysfunction after liver transplantation and surgery.
文摘目的:检测大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期海马组织中含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin-like and metalloproteinase with thrombospondin type l motifs,ADAMTS-1)在基底动脉中的表达,分析其与大鼠SAH后急性脑血管痉挛(cerebral vasospasm,CVS)的相关性,探讨其在SAH后早期脑损伤(earlybrain injury,EBI)中的作用。方法:健康雄性成年SD大鼠108只,体质量250～300g,随机分为SAH组(n=90)和假手术组(sham组,n=18)。SAH组取大鼠自体动脉血,用视交叉池注血法建立大鼠SAH模型(sham组注入等量0.9%氯化钠液)。将SAH组随机分为6h、12h、24h、48h、72h5个亚组,每个亚组18只,分别在相应时间点处死。用蛋白质印迹(Western-blot)方法及实时荧光定量逆转录-聚合酶链反应(RT-PCR)法检测SAH各亚组及sham组基底动脉ADAMTS-1的表达,同时用HE染色法对基底动脉进行形态学观察。探讨ADAMTS-1与实验性大鼠SAH后急性CVS的相关性。结果:与sham组相比,SAH 6h亚组基底动脉ADAMTS-1表达无显著差异;12h亚组基底动脉ADAMTS-1蛋白表达显著增高,24h亚组最高,48h亚组、72h亚组逐渐下降,但仍维持在较高水平。与sham组相比,SAH 6h亚组大鼠基底动脉变化不明显;12h亚组大鼠基底动脉管腔缩小,管壁增厚;24h亚组基底动脉痉挛最为明显;48h亚组基底动脉痉挛较24h亚组减轻;与24h亚组、48h亚组相比,72h亚组基底动脉管腔直径更大、管壁厚度更薄。ADAMTS-1蛋白表达与SAH后急性CVS呈正相关(r=0.916,P=0.003)。结论:大鼠SAH后早期基底动脉ADAMTS-1表达与急性CVS正相关,提示ADAMTS-1可能参与大鼠SAH后EBI的病理过程。
