目的研究人脑胶质瘤中含血小板结合蛋白基序的解聚素金属4(ADAMTS4)蛋白酶和ADAMTS5蛋白酶的表达及其与胶质瘤病理分级之间的关系。方法采用免疫组化Envision二步法检测ADAMTS4及ADAMTS5蛋白酶在44例不同级别脑胶质瘤、11例瘤周脑组织...目的研究人脑胶质瘤中含血小板结合蛋白基序的解聚素金属4(ADAMTS4)蛋白酶和ADAMTS5蛋白酶的表达及其与胶质瘤病理分级之间的关系。方法采用免疫组化Envision二步法检测ADAMTS4及ADAMTS5蛋白酶在44例不同级别脑胶质瘤、11例瘤周脑组织中的表达,计算阳性细胞百分率,并通过Image Pro Plusversion 6.0(IPP)图像分析软件测量计算其平均光密度(MOD)值。结果 (1)ADAMTS4和ADAMTS5蛋白酶在瘤周脑组织中不表达或极低表达,而在胶质瘤组织中高表达,为棕黄色,主要表达定位于细胞外基质及细胞质中,两组差异有统计学意义(P<0.05)。进一步研究显示,其蛋白表达量随着肿瘤级别的升高而升高,WHO分级中低级别、高级别间差异有统计学意义(P<0.05)。(2)ADAMTS4与ADAMTS5蛋白酶在胶质瘤中表达呈正相关性(χ~2=5.614,r=0.357,P<0.05)。结论(1)ADAMTS4、ADAMTS5蛋白表达量随着胶质瘤级别的升高而升高,提示了ADAMTS4及ADAMTS5蛋白酶在胶质瘤的进展、侵袭中发挥着重要作用。(2)ADAMTS4与ADAMTS5蛋白表达呈正相关性,揭示了在胶质瘤的发生发展中这两种蛋白酶可能互相协同,两者的过表达共同促进了胶质瘤的侵袭。展开更多
骨关节炎(OA)是一种普遍的退行性关节疾病,其特征是软骨退化和关节炎症。血小板结合蛋白基序的解聚蛋白样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motifs,AD⁃AMTS)家族成员在OA的发病机制中受到了广泛关注...骨关节炎(OA)是一种普遍的退行性关节疾病,其特征是软骨退化和关节炎症。血小板结合蛋白基序的解聚蛋白样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motifs,AD⁃AMTS)家族成员在OA的发病机制中受到了广泛关注,尤其是ADAMTS⁃4和ADAMTS⁃5,它们降解软骨蛋白聚糖活性远高于其他成员。蛋白聚糖是ECM的重要组成部分,蛋白聚糖的降解导致软骨的结构和功能破坏,是OA发展的关键因素。本文综述了ADAMTS⁃4和ADAMTS⁃5的结构和功能,重点解析二者底物切割位点的序列选择性、三维构象偏好及翻译后修饰、变构效应,和微环境信号对其蛋白水解活性的多层次调控机制,同时回顾了国内外学者对其靶向药的研究及未来展望。展开更多
背景:目前对骨关节患者滑膜、关节软骨中相关降解酶的研究较多,对关节液中相关因子的检测亦有报道,但有关不同病变分期相关因子表达情况的报道较少,且其与病变程度相关性研究报道亦相对较少。目的:检测不同分期骨关节炎患者关节液中细...背景:目前对骨关节患者滑膜、关节软骨中相关降解酶的研究较多,对关节液中相关因子的检测亦有报道,但有关不同病变分期相关因子表达情况的报道较少,且其与病变程度相关性研究报道亦相对较少。目的:检测不同分期骨关节炎患者关节液中细胞外调节蛋白激酶、基质金属蛋白酶13和人类含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶4/5(a disintegrin and metalloproteinase with thrombospondin-like motifs,ADAMTS4/5)的表达。方法:选择2016年10月至2017年12月在石河子大学医学院第一附属医院骨科行关节镜手术的骨关节炎患者94例,根据临床症状与K-L X射线分级分为早期组(n=27)、中期组(n=32)、晚期组(n=35);选择行截肢的健康患者、单纯膝外伤行关节镜检查者及自愿参与试验的门诊体检者10例,作为对照组。采集4组受试者关节液,采用荧光定量PCR法和ELISA法检测细胞外调节蛋白激酶、基质金属蛋白酶13和ADAMTS4/5的表达情况。试验经石河子大学医学院第一附属医院医学伦理委员会批准,批准号:2017-052-01。结果与结论:①荧光定量PCR检测:早、中、晚期组的各基因表达均高于对照组(P<0.001),早、中、晚期组的细胞外调节蛋白激酶、基质金属蛋白酶13基因表达呈逐渐上升趋势(P<0.01),早期组ADAMTS4/5基因表达高于中、晚期组(P<0.01);②ELISA检测:早、中、晚期组的关节液中各因子表达均高于对照组(P<0.001),早、中、晚期组的细胞外调节蛋白激酶、基质金属蛋白酶13表达呈逐渐上升趋势(P<0.01),早期组ADAMTS4/5表达高于中、晚期组(P<0.01);③相关性分析:细胞外调节蛋白激酶与基质金属蛋白酶13表达水平呈正相关关系(P<0.01),ADAMTS4与ADAMTS5表达呈正相关关系(P<0.01),ADAMTS4、ADAMTS5与细胞外调节蛋白激酶、基质金属蛋白酶13表达水平呈负相关关系(P<0.05);④结果表明:细胞外调节蛋白激酶、基质金属蛋白酶13及ADAMTS4/5的表达与膝骨性关节炎临床症状较为密切,研究这些因子在骨性关节炎不同分期中的分子机制,有望为临床诊断及预后判定提供一定的依据。展开更多
Objective To observe the efficacy of knee-balancing manipulation plus heat-sensitive moxibustion in treating knee osteoarthritis(KOA)and its impact on the expression of C-telopeptide of type I collagen(CTX-Ⅰ),tartrat...Objective To observe the efficacy of knee-balancing manipulation plus heat-sensitive moxibustion in treating knee osteoarthritis(KOA)and its impact on the expression of C-telopeptide of type I collagen(CTX-Ⅰ),tartrate-resistant acid phosphatase 5b(TRACP-5b),A disintegrin and metalloproteinase with thrombospondin motifs 4(ADAMTS-4),and matrix metalloproteinase 3(MMP-3).Methods A total of 134 unilateral KOA patients were randomized into a knee-balancing group,a heat-sensitive moxibustion group,and a joint intervention group.The knee-balancing group received knee-balancing Tuina(Chinese therapeutic massage)manipulation for treatment.The heat-sensitive moxibustion group received heat-sensitive moxibustion treatment.The joint intervention group received the heat-sensitive moxibustion in addition to the knee-balancing manipulation.The intervention period lasted for four weeks.After the treatment,and at the 2-week and 6-week follow-ups,the three groups were assessed using the visual analog scale(VAS)for knee joint pain and Western Ontario and McMaster Universities arthritis index(WOMAC),and clinical efficacy was also evaluated.The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3.Results The knee-balancing group had 44 participants,but one dropped out;there was no dropout case among the 44 participants in the heat-sensitive moxibustion group;among the 46 participants in the joint intervention group,two cases dropped out.After the treatment,and at the 2-week and 6-week follow-ups,the total effective rate was found higher in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups(P<0.05).Compared with the baseline,the VAS and WOMAC scores and the serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 decreased significantly in all three groups after treatment and at the 2-week and 6-week follow-ups(P<0.05).At the same three time points,the VAS and WOMAC scores and serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 were lower in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups(P<0.001).Conclusion Either used alone or combined,the knee-balancing manipulation and heat-sensitive moxibustion therapy can improve the symptoms and down-regulate the serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 in KOA patients,producing durable efficacy;nevertheless,a more significant efficacy can be achieved by combining the two methods.展开更多
文摘目的研究人脑胶质瘤中含血小板结合蛋白基序的解聚素金属4(ADAMTS4)蛋白酶和ADAMTS5蛋白酶的表达及其与胶质瘤病理分级之间的关系。方法采用免疫组化Envision二步法检测ADAMTS4及ADAMTS5蛋白酶在44例不同级别脑胶质瘤、11例瘤周脑组织中的表达,计算阳性细胞百分率,并通过Image Pro Plusversion 6.0(IPP)图像分析软件测量计算其平均光密度(MOD)值。结果 (1)ADAMTS4和ADAMTS5蛋白酶在瘤周脑组织中不表达或极低表达,而在胶质瘤组织中高表达,为棕黄色,主要表达定位于细胞外基质及细胞质中,两组差异有统计学意义(P<0.05)。进一步研究显示,其蛋白表达量随着肿瘤级别的升高而升高,WHO分级中低级别、高级别间差异有统计学意义(P<0.05)。(2)ADAMTS4与ADAMTS5蛋白酶在胶质瘤中表达呈正相关性(χ~2=5.614,r=0.357,P<0.05)。结论(1)ADAMTS4、ADAMTS5蛋白表达量随着胶质瘤级别的升高而升高,提示了ADAMTS4及ADAMTS5蛋白酶在胶质瘤的进展、侵袭中发挥着重要作用。(2)ADAMTS4与ADAMTS5蛋白表达呈正相关性,揭示了在胶质瘤的发生发展中这两种蛋白酶可能互相协同,两者的过表达共同促进了胶质瘤的侵袭。
文摘骨关节炎(OA)是一种普遍的退行性关节疾病,其特征是软骨退化和关节炎症。血小板结合蛋白基序的解聚蛋白样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motifs,AD⁃AMTS)家族成员在OA的发病机制中受到了广泛关注,尤其是ADAMTS⁃4和ADAMTS⁃5,它们降解软骨蛋白聚糖活性远高于其他成员。蛋白聚糖是ECM的重要组成部分,蛋白聚糖的降解导致软骨的结构和功能破坏,是OA发展的关键因素。本文综述了ADAMTS⁃4和ADAMTS⁃5的结构和功能,重点解析二者底物切割位点的序列选择性、三维构象偏好及翻译后修饰、变构效应,和微环境信号对其蛋白水解活性的多层次调控机制,同时回顾了国内外学者对其靶向药的研究及未来展望。
文摘背景:目前对骨关节患者滑膜、关节软骨中相关降解酶的研究较多,对关节液中相关因子的检测亦有报道,但有关不同病变分期相关因子表达情况的报道较少,且其与病变程度相关性研究报道亦相对较少。目的:检测不同分期骨关节炎患者关节液中细胞外调节蛋白激酶、基质金属蛋白酶13和人类含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶4/5(a disintegrin and metalloproteinase with thrombospondin-like motifs,ADAMTS4/5)的表达。方法:选择2016年10月至2017年12月在石河子大学医学院第一附属医院骨科行关节镜手术的骨关节炎患者94例,根据临床症状与K-L X射线分级分为早期组(n=27)、中期组(n=32)、晚期组(n=35);选择行截肢的健康患者、单纯膝外伤行关节镜检查者及自愿参与试验的门诊体检者10例,作为对照组。采集4组受试者关节液,采用荧光定量PCR法和ELISA法检测细胞外调节蛋白激酶、基质金属蛋白酶13和ADAMTS4/5的表达情况。试验经石河子大学医学院第一附属医院医学伦理委员会批准,批准号:2017-052-01。结果与结论:①荧光定量PCR检测:早、中、晚期组的各基因表达均高于对照组(P<0.001),早、中、晚期组的细胞外调节蛋白激酶、基质金属蛋白酶13基因表达呈逐渐上升趋势(P<0.01),早期组ADAMTS4/5基因表达高于中、晚期组(P<0.01);②ELISA检测:早、中、晚期组的关节液中各因子表达均高于对照组(P<0.001),早、中、晚期组的细胞外调节蛋白激酶、基质金属蛋白酶13表达呈逐渐上升趋势(P<0.01),早期组ADAMTS4/5表达高于中、晚期组(P<0.01);③相关性分析:细胞外调节蛋白激酶与基质金属蛋白酶13表达水平呈正相关关系(P<0.01),ADAMTS4与ADAMTS5表达呈正相关关系(P<0.01),ADAMTS4、ADAMTS5与细胞外调节蛋白激酶、基质金属蛋白酶13表达水平呈负相关关系(P<0.05);④结果表明:细胞外调节蛋白激酶、基质金属蛋白酶13及ADAMTS4/5的表达与膝骨性关节炎临床症状较为密切,研究这些因子在骨性关节炎不同分期中的分子机制,有望为临床诊断及预后判定提供一定的依据。
文摘Objective To observe the efficacy of knee-balancing manipulation plus heat-sensitive moxibustion in treating knee osteoarthritis(KOA)and its impact on the expression of C-telopeptide of type I collagen(CTX-Ⅰ),tartrate-resistant acid phosphatase 5b(TRACP-5b),A disintegrin and metalloproteinase with thrombospondin motifs 4(ADAMTS-4),and matrix metalloproteinase 3(MMP-3).Methods A total of 134 unilateral KOA patients were randomized into a knee-balancing group,a heat-sensitive moxibustion group,and a joint intervention group.The knee-balancing group received knee-balancing Tuina(Chinese therapeutic massage)manipulation for treatment.The heat-sensitive moxibustion group received heat-sensitive moxibustion treatment.The joint intervention group received the heat-sensitive moxibustion in addition to the knee-balancing manipulation.The intervention period lasted for four weeks.After the treatment,and at the 2-week and 6-week follow-ups,the three groups were assessed using the visual analog scale(VAS)for knee joint pain and Western Ontario and McMaster Universities arthritis index(WOMAC),and clinical efficacy was also evaluated.The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3.Results The knee-balancing group had 44 participants,but one dropped out;there was no dropout case among the 44 participants in the heat-sensitive moxibustion group;among the 46 participants in the joint intervention group,two cases dropped out.After the treatment,and at the 2-week and 6-week follow-ups,the total effective rate was found higher in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups(P<0.05).Compared with the baseline,the VAS and WOMAC scores and the serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 decreased significantly in all three groups after treatment and at the 2-week and 6-week follow-ups(P<0.05).At the same three time points,the VAS and WOMAC scores and serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 were lower in the joint intervention group than in the knee-balancing and heat-sensitive moxibustion groups(P<0.001).Conclusion Either used alone or combined,the knee-balancing manipulation and heat-sensitive moxibustion therapy can improve the symptoms and down-regulate the serum levels of CTX-Ⅰ,TRACP-5b,ADAMTS-4,and MMP-3 in KOA patients,producing durable efficacy;nevertheless,a more significant efficacy can be achieved by combining the two methods.
