Snake venom disintegrins,through their inhibition of integrin-related binding,effectively impede both cell-cell and cell-matrix interactions as well as signal transduction pathways,rendering them promising candidates ...Snake venom disintegrins,through their inhibition of integrin-related binding,effectively impede both cell-cell and cell-matrix interactions as well as signal transduction pathways,rendering them promising candidates for lead therapeutics across a spectrum of diseases.This study aimed to conduct a comprehensive bibliometric analysis,elucidating recent trends in disintegrin research.Using relevant keywords,we meticulously explored the Web of Science Core Collection(WOSCC)database.Employing CiteSpace and VOSviewer,we conducted an exhaustive analysis,encompassing 142 documents published between 2009 and 2023.These publications,dispersed across 74 journals,involved 670 authors representing 207 institutes spanning 42 countries.Notably,the United States contributed the highest number of records,with Texas A&M University emerging as the most prolific institution.Within this landscape,Elda E.Sanchez emerged as the foremost author,and Toxicon emerged as the predominant journal.Keyword analysis underscored prevailing research foci,with an emphasis on expression,in vitro experimentation,and ASP-containing peptides.This study presented a comprehensive overview of disintegrin research globally,spanning the period from 2009 to 2023,and held potential utility in guiding future research endeavors.By identifying current research hotspots,our findings offered invaluable insights to shape forthcoming investigations in this dynamic field.展开更多
Objective： To investigate the effects of rAdinbitor on the adhesion and proliferation of human hepatoma cell strain 8MMC-7721. Methods： Cell adhesion assay was used to observe the effect of rAdinbitor on the adhesio...Objective： To investigate the effects of rAdinbitor on the adhesion and proliferation of human hepatoma cell strain 8MMC-7721. Methods： Cell adhesion assay was used to observe the effect of rAdinbitor on the adhesion of 8MMC-7721 cells to fibronectin （FN）. Crystal violet staining was performed to detect the influence of rAdinbitor on the adhesion of 8MMC- 7721 cells. MTT assay was employed to detect the inhibitory effects of different concentration of rAdinbitor on the proliferation of 8MMC-7721 cells. The morphologic changes of the control 8MMC-7721 cells and the apoptotic cells induced by 200μg/mL rAdinbitor for 36 h were observed under light microscope after HE staining. Flow cytometry analysis was applied to determine the apoptosis rate of 8MMC-7721 cells. Results： （1） FN promoted the adhesion of human hepatoma cell strain 8MMC-7721 in a dose-dependent manner. （2） rAdinbitor could dose-dependently inhibit the adhesion of SMMC-7721 cells to FN. The higher the concentration was, the stronger the inhibition was. There was significant difference among the groups （P 〈 0.05）. （3） rAdinbitor had a strong inhibition on the proliferation of 8MMC-7721 cells and showed a dose-dependent manner （P 〈 0.05）. After a 48 h exposure, the IC50 value of rAdinbitor was 177.83 μg/mL. （4） After exposure of 8MMC-7721 cells to 200μg/mL rAdinbitor for 36 h, the early morphologic changes appeared and the apoptosis rate was 20.68%, significantly higher than that of the control group （2.38%, P 〈 0.05）. Conclusion： rAdinbitor can dose-dependently inhibit the 8MMC-7721 cells adhesion to FN, and can inhibit the proliferation in dose-dependent manner and promote their apoptosis.展开更多
The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a mo...The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain （NICD）. A Disintegrin and Metalloprotease 10 （ADAM10） might be a physiological rate-limiting $2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is cdtical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAMIO mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 （E14.5） to postnatal day 1 （P1）. ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin （neural stem cell marker）, Tujl （mature neuron marker）, and S100β （gila marker） showed that ADAM10 expression highly matched that of S10013 and partially matched that of Tujl at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.展开更多
Our findings represent the first report of the antitumor activity of the disintegrin-like components from the venom of Armenian viper (M. raddei). The venom of M. raddei was separated by reverse phase high-performance...Our findings represent the first report of the antitumor activity of the disintegrin-like components from the venom of Armenian viper (M. raddei). The venom of M. raddei was separated by reverse phase high-performance liquid chroma-tography (RP HPLC), and individual fractions were analyzed for disintegrin activity. Disintegrin-like components from the venom of M. raddei, by blocking integrins on breast cancer cells (MDA-MB-435), not only interferes with adhesion of breast cancer cells to the extracellular matrix, but also inhibits cellular mobility which is essential for cancer invasion. These effects seriously curtail the metastatic capability of the MDA-MB-435 cells.展开更多
Integrins mediate cell adhesion to the extracellular matrix (ECM). In particular, integrin alphavbeta3 recognizes the RGD motif as a ligand-binding site on various extracellular molecules of the extracellular matrix. ...Integrins mediate cell adhesion to the extracellular matrix (ECM). In particular, integrin alphavbeta3 recognizes the RGD motif as a ligand-binding site on various extracellular molecules of the extracellular matrix. Integrin aphavbeta3 has been associated with high malignant potential in breast cancer cells, and has signalized the onset of widespread metastasis. In recent years, several antagonists of integrin alphavbeta3, including snake venom disintegrins, have been used as potential anti-cancer agents. In the present work, the effect of contortrostatin, a disintegrin isolated from the venom of the snake Agkistrodon contortrix, was studied on primary cultures of human breast cancer cell. Scanning and transmission electron microscopy were employed in order to examine alterations in cell morphology and fluorescent microscopy and visualize changes in distribution of integrin alphavbeta3 and talin. Fluorescent localization of caspase 8 was made in order to visualize any sign of proapoptotosis and western immunoblotting of integrin, talin and annexin was undertaken in order to identify changes. The results suggest that the snake venom contortrostatin seriously affects cell morphology, adhesion and mobility and induces breast cancer cells to apoptosis.展开更多
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:分析4例携带血管性血友病因子裂解酶13(a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13,ADAMTS13)去整合素样结构域杂合突变的血栓患者其基因型和表型特征,探讨ADAMTS13功能缺陷与血栓形成之间的关联...目的:分析4例携带血管性血友病因子裂解酶13(a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13,ADAMTS13)去整合素样结构域杂合突变的血栓患者其基因型和表型特征,探讨ADAMTS13功能缺陷与血栓形成之间的关联。方法:通过易栓症基因Panel检测筛查血栓患者的易栓症相关基因突变,纳入4个携带ADAMTS13去整合素样结构域突变的易栓症家系。采用凝固法检测患者的凝血功能,使用免疫比浊法测定血管性血友病因子(von Willebrand factor,vWF)抗原和活性,酶联免疫吸附法检测vWF的胶原结合能力。通过十二烷基硫酸钠-琼脂糖凝胶电泳分析vWF多聚体的分布情况并进行灰度值半定量分析。采用荧光共振能量转移法测定血浆中ADAMTS13活性,酶联免疫吸附法检测ADAMTS13抗原水平。使用PyMOL软件对野生型及突变型ADAMTS13蛋白的三维结构进行对比分析。结果:4个家系的先证者均经历不同程度的血栓事件,包括脑静脉窦血栓、肺栓塞及下肢深静脉血栓。ADAMTS13蛋白去整合素样结构域突变约占ADAMTS13单杂合突变的4/87。遗传分析显示,4例先证者均携带ADAMTS13基因去整合素样结构域单杂合突变(p.Pro301Ala、p.Pro301Arg、p.Arg349Cys),其中p.Pro301Ala和p.Pro301Arg为首次报道突变。凝血功能检测结果表明,4例患者ADAMTS13活性和抗原水平显著降低(Act为57.42%~72.88%,Ag为66.94%~78.34%),vWF活性和抗原水平升高(Act为158.2%~213.7%,Ag为167.2%~216.6%)。vWF多聚体电泳分析显示,患者血浆中高分子量多聚体(high-molecular-weight multimers,HMWMs)比例显著增加(灰度值166.6~218.9比117.4),提示HMWMs较正常人明显增多。结构分析进一步表明,突变位点位于ADAMTS13蛋白去整合素样结构域的关键区域,可能破坏蛋白稳定性及与vWF的结合能力。结论:本研究首次报道了位于ADAMTS13蛋白去整合素样结构域上的2个新突变(Pro301Ala和Pro301Arg),并再次验证了已知突变Arg349Cys的致病特性。结果证实这些突变可导致ADAMTS13蛋白表达水平下降,并进一步引起其酶活性的显著降低,表现为对vWF高分子量多聚体的裂解能力减弱,功能试验证实患者体内存在异常增多的vWF多聚体,破坏了ADAMTS13-vWF轴的动态平衡,从而增加血栓形成的风险。展开更多
Ventricular remodeling （VR） after myocardial infarction （MI） makes a full impact on left ventricular dilation and dysfunction, severe arrhythmias and even sudden death. Thus it is very interesting and instructive ...Ventricular remodeling （VR） after myocardial infarction （MI） makes a full impact on left ventricular dilation and dysfunction, severe arrhythmias and even sudden death. Thus it is very interesting and instructive to study the underlying regulatory mechanism for VR. Recently, evidenceI suggests that tumor necrosis factor-α （TNF-α） activity can independently influence VR, and aggravate myocardial dysfunction and cell death in the ventricle. The activation of pro-TNF〈t is adjusted by a disintegrin metalloproteinase （ADAM） 10 and ADAM17, the latter might take part in extracellular matrix （ECM） modulation in the borderline region of cardiac infarction.2 However, little is known about the relationship between ADAMsl0, 17 expressions and TNF-α activity in the process of VR after MI. The present study tested the hypothesis in rats that the interaction between ADAMsl0, 17 expressions and TNF-α activity was a contributory mechanism for VR of the healing myocardium, and metoprolol treatment might ameliorate VR inhibiting the mechanism.展开更多
目的 探讨老年终末期肾病(end-stage renal disease,ESRD)血液透析患者中血清葡萄糖调节蛋白78(glucose regulatory protein 78,GRP78)、血管性血友病因子裂解蛋白酶(a disintegrin like and metalloproteinase with thrombospondin typ...目的 探讨老年终末期肾病(end-stage renal disease,ESRD)血液透析患者中血清葡萄糖调节蛋白78(glucose regulatory protein 78,GRP78)、血管性血友病因子裂解蛋白酶(a disintegrin like and metalloproteinase with thrombospondin type 1 motifs 13,ADAMTS13)表达对心脏瓣膜钙化的预测价值。方法 选取2022年5月至2024年2月在蒙城县中医院(亳州市第二中医院)接受血液透析治疗的老年ESRD患者86例,心脏超声仪检查确定其中36例发生心脏瓣膜钙化(钙化组)、50例未发生心脏瓣膜钙化(无钙化组)。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)对血清GRP78、ADAMTS13水平进行检测;采用多因素Logistic回归分析不同临床资料与老年ESRD血液透析患者心脏瓣膜钙化的关系;采用受试者工作特征曲线分析血清GRP78、ADAMTS13单独及联合预测老年ESRD血液透析患者心脏瓣膜钙化的价值。结果 钙化组老年ESRD血液透析患者血清GRP78水平[(4.59±1.12)μg/L比(2.91±0.73)μg/L]、透析龄[(72.86±12.73)个月比(60.40±15.75)个月]、钙镁比(2.47±0.42比2.16±0.40)高于无钙化组,ADAMTS13水平[(522.58±129.05)μg/L比(864.52±221.13)μg/L]低于无钙化组(P<0.05)。血清GRP78、ADAMTS13与老年ESRD血液透析患者心脏瓣膜钙化独立相关(P<0.05)。血清GRP78、ADAMTS13单独及联合预测老年ESRD血液透析患者心脏瓣膜钙化的曲线下面积(area under the curve,AUC)分别为0.861、0.833、0.939,联合预测的AUC高于单独预测的AUC(Z=2.206、2.998,P<0.05)。结论 发生心脏瓣膜钙化的老年ESRD血液透析患者中血清GRP78高表达,ADAMTS13低表达,二者联合可有效提升心脏瓣膜钙化的预测效能。展开更多
基金Startup Fund for Scientific Research,Fujian Medical University(Grant No.2022QH1216)。
文摘Snake venom disintegrins,through their inhibition of integrin-related binding,effectively impede both cell-cell and cell-matrix interactions as well as signal transduction pathways,rendering them promising candidates for lead therapeutics across a spectrum of diseases.This study aimed to conduct a comprehensive bibliometric analysis,elucidating recent trends in disintegrin research.Using relevant keywords,we meticulously explored the Web of Science Core Collection(WOSCC)database.Employing CiteSpace and VOSviewer,we conducted an exhaustive analysis,encompassing 142 documents published between 2009 and 2023.These publications,dispersed across 74 journals,involved 670 authors representing 207 institutes spanning 42 countries.Notably,the United States contributed the highest number of records,with Texas A&M University emerging as the most prolific institution.Within this landscape,Elda E.Sanchez emerged as the foremost author,and Toxicon emerged as the predominant journal.Keyword analysis underscored prevailing research foci,with an emphasis on expression,in vitro experimentation,and ASP-containing peptides.This study presented a comprehensive overview of disintegrin research globally,spanning the period from 2009 to 2023,and held potential utility in guiding future research endeavors.By identifying current research hotspots,our findings offered invaluable insights to shape forthcoming investigations in this dynamic field.
文摘Objective： To investigate the effects of rAdinbitor on the adhesion and proliferation of human hepatoma cell strain 8MMC-7721. Methods： Cell adhesion assay was used to observe the effect of rAdinbitor on the adhesion of 8MMC-7721 cells to fibronectin （FN）. Crystal violet staining was performed to detect the influence of rAdinbitor on the adhesion of 8MMC- 7721 cells. MTT assay was employed to detect the inhibitory effects of different concentration of rAdinbitor on the proliferation of 8MMC-7721 cells. The morphologic changes of the control 8MMC-7721 cells and the apoptotic cells induced by 200μg/mL rAdinbitor for 36 h were observed under light microscope after HE staining. Flow cytometry analysis was applied to determine the apoptosis rate of 8MMC-7721 cells. Results： （1） FN promoted the adhesion of human hepatoma cell strain 8MMC-7721 in a dose-dependent manner. （2） rAdinbitor could dose-dependently inhibit the adhesion of SMMC-7721 cells to FN. The higher the concentration was, the stronger the inhibition was. There was significant difference among the groups （P 〈 0.05）. （3） rAdinbitor had a strong inhibition on the proliferation of 8MMC-7721 cells and showed a dose-dependent manner （P 〈 0.05）. After a 48 h exposure, the IC50 value of rAdinbitor was 177.83 μg/mL. （4） After exposure of 8MMC-7721 cells to 200μg/mL rAdinbitor for 36 h, the early morphologic changes appeared and the apoptosis rate was 20.68%, significantly higher than that of the control group （2.38%, P 〈 0.05）. Conclusion： rAdinbitor can dose-dependently inhibit the 8MMC-7721 cells adhesion to FN, and can inhibit the proliferation in dose-dependent manner and promote their apoptosis.
基金supported by the National Natural Science Foundation of China,No.30800322Shanghai Pujiang Program,No.08PJ1401300+4 种基金Shanghai Leading Academic Discipline Project,No.B111Ministry of Education Research Fund for New Teachers in Doctoral Program of Higher Educational Institutes,No.200802461050National Basic Research Program of China(973 Program),No.2011CB503703Ministry of Education Start Fund to Returned Overseas ScholarsZhuo Xue Program of Fudan University
文摘The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain （NICD）. A Disintegrin and Metalloprotease 10 （ADAM10） might be a physiological rate-limiting $2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is cdtical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAMIO mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 （E14.5） to postnatal day 1 （P1）. ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin （neural stem cell marker）, Tujl （mature neuron marker）, and S100β （gila marker） showed that ADAM10 expression highly matched that of S10013 and partially matched that of Tujl at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.
文摘Our findings represent the first report of the antitumor activity of the disintegrin-like components from the venom of Armenian viper (M. raddei). The venom of M. raddei was separated by reverse phase high-performance liquid chroma-tography (RP HPLC), and individual fractions were analyzed for disintegrin activity. Disintegrin-like components from the venom of M. raddei, by blocking integrins on breast cancer cells (MDA-MB-435), not only interferes with adhesion of breast cancer cells to the extracellular matrix, but also inhibits cellular mobility which is essential for cancer invasion. These effects seriously curtail the metastatic capability of the MDA-MB-435 cells.
文摘Integrins mediate cell adhesion to the extracellular matrix (ECM). In particular, integrin alphavbeta3 recognizes the RGD motif as a ligand-binding site on various extracellular molecules of the extracellular matrix. Integrin aphavbeta3 has been associated with high malignant potential in breast cancer cells, and has signalized the onset of widespread metastasis. In recent years, several antagonists of integrin alphavbeta3, including snake venom disintegrins, have been used as potential anti-cancer agents. In the present work, the effect of contortrostatin, a disintegrin isolated from the venom of the snake Agkistrodon contortrix, was studied on primary cultures of human breast cancer cell. Scanning and transmission electron microscopy were employed in order to examine alterations in cell morphology and fluorescent microscopy and visualize changes in distribution of integrin alphavbeta3 and talin. Fluorescent localization of caspase 8 was made in order to visualize any sign of proapoptotosis and western immunoblotting of integrin, talin and annexin was undertaken in order to identify changes. The results suggest that the snake venom contortrostatin seriously affects cell morphology, adhesion and mobility and induces breast cancer cells to apoptosis.
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:分析4例携带血管性血友病因子裂解酶13(a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13,ADAMTS13)去整合素样结构域杂合突变的血栓患者其基因型和表型特征,探讨ADAMTS13功能缺陷与血栓形成之间的关联。方法:通过易栓症基因Panel检测筛查血栓患者的易栓症相关基因突变,纳入4个携带ADAMTS13去整合素样结构域突变的易栓症家系。采用凝固法检测患者的凝血功能,使用免疫比浊法测定血管性血友病因子(von Willebrand factor,vWF)抗原和活性,酶联免疫吸附法检测vWF的胶原结合能力。通过十二烷基硫酸钠-琼脂糖凝胶电泳分析vWF多聚体的分布情况并进行灰度值半定量分析。采用荧光共振能量转移法测定血浆中ADAMTS13活性,酶联免疫吸附法检测ADAMTS13抗原水平。使用PyMOL软件对野生型及突变型ADAMTS13蛋白的三维结构进行对比分析。结果:4个家系的先证者均经历不同程度的血栓事件,包括脑静脉窦血栓、肺栓塞及下肢深静脉血栓。ADAMTS13蛋白去整合素样结构域突变约占ADAMTS13单杂合突变的4/87。遗传分析显示,4例先证者均携带ADAMTS13基因去整合素样结构域单杂合突变(p.Pro301Ala、p.Pro301Arg、p.Arg349Cys),其中p.Pro301Ala和p.Pro301Arg为首次报道突变。凝血功能检测结果表明,4例患者ADAMTS13活性和抗原水平显著降低(Act为57.42%~72.88%,Ag为66.94%~78.34%),vWF活性和抗原水平升高(Act为158.2%~213.7%,Ag为167.2%~216.6%)。vWF多聚体电泳分析显示,患者血浆中高分子量多聚体(high-molecular-weight multimers,HMWMs)比例显著增加(灰度值166.6~218.9比117.4),提示HMWMs较正常人明显增多。结构分析进一步表明,突变位点位于ADAMTS13蛋白去整合素样结构域的关键区域,可能破坏蛋白稳定性及与vWF的结合能力。结论:本研究首次报道了位于ADAMTS13蛋白去整合素样结构域上的2个新突变(Pro301Ala和Pro301Arg),并再次验证了已知突变Arg349Cys的致病特性。结果证实这些突变可导致ADAMTS13蛋白表达水平下降,并进一步引起其酶活性的显著降低,表现为对vWF高分子量多聚体的裂解能力减弱,功能试验证实患者体内存在异常增多的vWF多聚体,破坏了ADAMTS13-vWF轴的动态平衡,从而增加血栓形成的风险。
基金This work was supported by the grants from the National Natural Science Foundation of Chian(No.30470687)Heilongjiang Doctorate Foundation grant(No.SCX2005020)
文摘Ventricular remodeling （VR） after myocardial infarction （MI） makes a full impact on left ventricular dilation and dysfunction, severe arrhythmias and even sudden death. Thus it is very interesting and instructive to study the underlying regulatory mechanism for VR. Recently, evidenceI suggests that tumor necrosis factor-α （TNF-α） activity can independently influence VR, and aggravate myocardial dysfunction and cell death in the ventricle. The activation of pro-TNF〈t is adjusted by a disintegrin metalloproteinase （ADAM） 10 and ADAM17, the latter might take part in extracellular matrix （ECM） modulation in the borderline region of cardiac infarction.2 However, little is known about the relationship between ADAMsl0, 17 expressions and TNF-α activity in the process of VR after MI. The present study tested the hypothesis in rats that the interaction between ADAMsl0, 17 expressions and TNF-α activity was a contributory mechanism for VR of the healing myocardium, and metoprolol treatment might ameliorate VR inhibiting the mechanism.
文摘目的 探讨老年终末期肾病(end-stage renal disease,ESRD)血液透析患者中血清葡萄糖调节蛋白78(glucose regulatory protein 78,GRP78)、血管性血友病因子裂解蛋白酶(a disintegrin like and metalloproteinase with thrombospondin type 1 motifs 13,ADAMTS13)表达对心脏瓣膜钙化的预测价值。方法 选取2022年5月至2024年2月在蒙城县中医院(亳州市第二中医院)接受血液透析治疗的老年ESRD患者86例,心脏超声仪检查确定其中36例发生心脏瓣膜钙化(钙化组)、50例未发生心脏瓣膜钙化(无钙化组)。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)对血清GRP78、ADAMTS13水平进行检测;采用多因素Logistic回归分析不同临床资料与老年ESRD血液透析患者心脏瓣膜钙化的关系;采用受试者工作特征曲线分析血清GRP78、ADAMTS13单独及联合预测老年ESRD血液透析患者心脏瓣膜钙化的价值。结果 钙化组老年ESRD血液透析患者血清GRP78水平[(4.59±1.12)μg/L比(2.91±0.73)μg/L]、透析龄[(72.86±12.73)个月比(60.40±15.75)个月]、钙镁比(2.47±0.42比2.16±0.40)高于无钙化组,ADAMTS13水平[(522.58±129.05)μg/L比(864.52±221.13)μg/L]低于无钙化组(P<0.05)。血清GRP78、ADAMTS13与老年ESRD血液透析患者心脏瓣膜钙化独立相关(P<0.05)。血清GRP78、ADAMTS13单独及联合预测老年ESRD血液透析患者心脏瓣膜钙化的曲线下面积(area under the curve,AUC)分别为0.861、0.833、0.939,联合预测的AUC高于单独预测的AUC(Z=2.206、2.998,P<0.05)。结论 发生心脏瓣膜钙化的老年ESRD血液透析患者中血清GRP78高表达,ADAMTS13低表达,二者联合可有效提升心脏瓣膜钙化的预测效能。
