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
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
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
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
Objective: To investigate the effects of rAdinbitor on the adhesion and proliferation of human hepatoma cell strain SMMC-7721. Methods: Cell adhesion assay was used to observe the effect of rAdinbitor on the adhesion ...Objective: To investigate the effects of rAdinbitor on the adhesion and proliferation of human hepatoma cell strain SMMC-7721. Methods: Cell adhesion assay was used to observe the effect of rAdinbitor on the adhesion of SMMC-7721 cells to fibronectin (FN). Crystal violet staining was performed to detect the influence of rAdinbitor on the adhesion of SMMC-7721 cells. MTT assay was employed to detect the inhibitory effects of different concentration of rAdinbitor on the proliferation of SMMC-7721 cells. The morphologic changes of the control SMMC-7721 cells and the apoptotic cells induced by 200 μg/mL rAdinbitor for 36 h were observed under light microscope after HE staining. Flow cytometry analysis was applied to determine the apoptosis rate of SMMC-7721 cells. Results: (1) FN promoted the adhesion of human hepatoma cell strain SMMC-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 SMMC-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 SMMC-7721 cells to 200 μg/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 SMMC-7721 cells adhesion to FN, and can inhibit the proliferation in dose-dependent manner and promote their apoptosis.展开更多
目的:研究丁酸钠、曲古抑菌素A(trichostatin A,TSA)及腺病毒E1A相关的300 kD蛋白(adenoviral E1A binding protein of 300 kD,P300)介导的组蛋白乙酰化在人非小细胞肺癌A549细胞及人支气管上皮BEAS-2B细胞中对哮喘易感的解整合素金属...目的:研究丁酸钠、曲古抑菌素A(trichostatin A,TSA)及腺病毒E1A相关的300 kD蛋白(adenoviral E1A binding protein of 300 kD,P300)介导的组蛋白乙酰化在人非小细胞肺癌A549细胞及人支气管上皮BEAS-2B细胞中对哮喘易感的解整合素金属蛋白酶33(a disintegrin and metalloproteinase 33,ADAM33)基因表达的影响。方法:将A549细胞及BEAS-2B细胞分别分为丁酸钠对照组(双蒸水处理)和1、2.5、5 mmol/L丁酸钠组,TSA对照组(0.1%二甲基亚砜处理)和0.2、0.4、0.8μmol/L TSA组,按照组别分别予以相应处理;另将BEAS-2B细胞分为对照组(转染P300突变质粒)和P300组(转染P300表达质粒);采用双荧光素酶报告基因法分析ADAM33启动子活性的变化,实时荧光定量PCR(quantitative real time-PCR,qRT-PCR)检测ADAM33 mRNA表达,蛋白质印迹法检测ADAM33蛋白表达。结果:在人非小细胞肺癌A549细胞中,与对照组相比,1 mmol/L丁酸钠组及0.2μmol/L TSA组ADAM33基因启动子活性明显降低(P<0.01);在BEAS-2B细胞中,与对照组相比,1 mmol/L丁酸钠组及0.2μmol/L TSA组ADAM33基因启动子活性、mRNA及蛋白相对表达水平明显降低(P<0.05或P<0.01)。加大丁酸钠、TSA药物浓度,ADAM33表达无显著差异。在人支气管上皮BEAS-2B细胞中,与对照组相比,P300组ADAM33启动子活性、mRNA和蛋白相对表达水平明显降低(P<0.05)。结论:丁酸钠、TSA通过组蛋白乙酰化降低人非小细胞肺癌A549细胞和人支气管上皮BEAS-2B细胞中ADAM33表达,P300通过组蛋白乙酰化降低人支气管上皮BEAS-2B细胞中ADAM33表达。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
目的探讨去整合素金属蛋白酶10(a disintegrin and metalloprotease 10,ADAM10)和高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)与声门型喉癌患者病理特征及预后关系分析。方法回顾性收集2017年3月~2020年12月于南京医科...目的探讨去整合素金属蛋白酶10(a disintegrin and metalloprotease 10,ADAM10)和高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)与声门型喉癌患者病理特征及预后关系分析。方法回顾性收集2017年3月~2020年12月于南京医科大学附属南京医院确诊及治疗的声门型喉癌患者50例(观察组),另取相对喉癌组织切缘0.5cm以上部位标本作为对照组。观察并比较ADAM10和HMGB1在两组中的阳性表达率,分析其阳性表达与声门型喉癌患者的病理特征关系。单因素分析影响声门型喉癌预后的危险因素,Cox多因素回归分析声门型喉癌患者不良预后的独立危险因素。结果ADAM10和HMGB1在观察组的阳性表达率均高于对照组,差异均有统计学意义(P<0.05)。声门型喉癌组织中的ADAM10与淋巴结转移和T分级差异比较有统计学意义,而与年龄、性别、饮酒史、吸烟史、分化程度差异比较无统计学意义(P>0.05);HMGB1与分化程度差异比较有统计学意义(P<0.05),而与年龄、性别、饮酒史、吸烟史、淋巴结转移、T分级差异比较无统计学意义(P>0.05)。单因素分析结果表明,淋巴结转移、T分级、分化程度、ADAM10、HMGB1是患者预后的影响因素。Cox多因素回归分析结果表明,淋巴结转移、T3+T4分级、低分化程度、ADAM10阳性、HMGB1阳性为声门型喉癌患者预后不良的独立影响因素(P<0.05)。结论ADAM10和HMGB1可作为声门型喉癌不良预后的风险评估指标。展开更多
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Objective: To investigate the effects of rAdinbitor on the adhesion and proliferation of human hepatoma cell strain SMMC-7721. Methods: Cell adhesion assay was used to observe the effect of rAdinbitor on the adhesion of SMMC-7721 cells to fibronectin (FN). Crystal violet staining was performed to detect the influence of rAdinbitor on the adhesion of SMMC-7721 cells. MTT assay was employed to detect the inhibitory effects of different concentration of rAdinbitor on the proliferation of SMMC-7721 cells. The morphologic changes of the control SMMC-7721 cells and the apoptotic cells induced by 200 μg/mL rAdinbitor for 36 h were observed under light microscope after HE staining. Flow cytometry analysis was applied to determine the apoptosis rate of SMMC-7721 cells. Results: (1) FN promoted the adhesion of human hepatoma cell strain SMMC-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 SMMC-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 SMMC-7721 cells to 200 μg/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 SMMC-7721 cells adhesion to FN, and can inhibit the proliferation in dose-dependent manner and promote their apoptosis.
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.
文摘目的探讨去整合素金属蛋白酶10(a disintegrin and metalloprotease 10,ADAM10)和高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)与声门型喉癌患者病理特征及预后关系分析。方法回顾性收集2017年3月~2020年12月于南京医科大学附属南京医院确诊及治疗的声门型喉癌患者50例(观察组),另取相对喉癌组织切缘0.5cm以上部位标本作为对照组。观察并比较ADAM10和HMGB1在两组中的阳性表达率,分析其阳性表达与声门型喉癌患者的病理特征关系。单因素分析影响声门型喉癌预后的危险因素,Cox多因素回归分析声门型喉癌患者不良预后的独立危险因素。结果ADAM10和HMGB1在观察组的阳性表达率均高于对照组,差异均有统计学意义(P<0.05)。声门型喉癌组织中的ADAM10与淋巴结转移和T分级差异比较有统计学意义,而与年龄、性别、饮酒史、吸烟史、分化程度差异比较无统计学意义(P>0.05);HMGB1与分化程度差异比较有统计学意义(P<0.05),而与年龄、性别、饮酒史、吸烟史、淋巴结转移、T分级差异比较无统计学意义(P>0.05)。单因素分析结果表明,淋巴结转移、T分级、分化程度、ADAM10、HMGB1是患者预后的影响因素。Cox多因素回归分析结果表明,淋巴结转移、T3+T4分级、低分化程度、ADAM10阳性、HMGB1阳性为声门型喉癌患者预后不良的独立影响因素(P<0.05)。结论ADAM10和HMGB1可作为声门型喉癌不良预后的风险评估指标。
