Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sect...Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.展开更多
Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detec...Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detect the expres- sions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE). The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results: The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% (64/72) in group ICC and 12.5% (2/16) in group NCE, P = 0.000; MMP-9: 94.4% (68/72) in group ICC and 43.8% (7/16) in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis (r = 0.296, P = 0.012) and stromal invasion (r = 0.257, P = 0.029). The expression of MMP-9 was positively correlated with FIGO stage (r = 0.329, P = 0.005) and histological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). Conclusion: The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.展开更多
Objective:The aim of the study was to investigate the expressions of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of MMP-2(TIMP-2) mRNA in transitional cell carcinomas of bladder and discuss their clinical s...Objective:The aim of the study was to investigate the expressions of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of MMP-2(TIMP-2) mRNA in transitional cell carcinomas of bladder and discuss their clinical significances.Methods:Using RT-PCR and real time quantitative PCR(RQ-PCR) technique,the expressions of MMP-2 and TIMP-2 mRNA of 45 cases of bladder carcinoma(tumor group) and 10 cases of normal bladder tissue(control group) were analyzed.Results:MMP-2 and TIMP-2 were not expressed in control group.MMP-2 was expressed in 30 cases tumor samples and TIMP-2 was expressed in 26 cases.The expression of MMP-2 mRNA in non-muscle invasive bladder cancers and grade I cancers was lower than that in muscle invasive bladder cancers and grades II-III cancers respectively.The differences were statistically significant(P<0.05).The expression of MMP-2 in recurrent patients was higher than that in incipient patients.TIMP-2 mRNA expression decreased with grades and stage.The expression of TIMP-2 in non-muscle invasive bladder cancers and grade I cancers was higher than that in muscle invasive bladder cancers and grades II-III cancers respectively.There was statistical difference between two groups(P < 0.05).TIMP-2 expression in incipient patients was higher than that in recurrent patients,but the difference was not significant(P>0.05).Conclusion:These results suggest that MMP-2 and TIMP-2 play an important role in the invasion step of transitional cell carcinoma of bladder.MMP-2 may become a new approach to the diagnosis of bladder carcinoma.展开更多
Objective:To investigate the expression and significance of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-13(MMP-13)in bullous pemphigoid(BP)skin lesions.Methods:Immunohistochemical SP method was used ...Objective:To investigate the expression and significance of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-13(MMP-13)in bullous pemphigoid(BP)skin lesions.Methods:Immunohistochemical SP method was used to detect the expression of MMP-2 and MMP-13 in 32 BP skin lesions,and compared with 15 normal skin tissues.Results:The expression of MMP-2 in the case group was significantly increased(38.56±10.06)compared to the normal control group(21.20±5.98);the expression of MMP-13 in the case group was significantly augmented(18.62±5.90)compared to the normal control group(11.47±8.484).The expressions of MMP-2 and MMP-13 in the skin lesions of patients with bullous pemphigoid were statistically different from those of normal people(both P<0.05).Compared with the expression of MMP-2 and MMP-13 in bullous pemphigoid,the expression of MMP-2 and MMP-13 was moderately correlated(correlation coefficient was 0.523).Conclusion:The expression of MMP-2 and MMP-13 is significantly increased in bullous pemphigoid skin lesions,suggesting that they may play an important role in the pathogenesis of BP.There is a certain correlation between the expression of MMP-2 and MMP-13,suggesting that the high expression of MMP-13 may play a role in the mechanism that further leads to the high expression of MMP-2.展开更多
Objective： To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 （MMP-2） and tissue inhibitors of matrix metalloproteinase-2 （TIMP-2） and on cell migration of cultur...Objective： To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 （MMP-2） and tissue inhibitors of matrix metalloproteinase-2 （TIMP-2） and on cell migration of cultured rat vascular smooth muscle cells （VSMCs）. Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods： Rat VSMCs were incubated with different concentrations of homocysteine （50-5000 μmol/L）. Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin （10^-9-10^-5 mol/L） were added when VSMCs were induced with 1 000 pmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results： Homocysteine （50-1000 μmol/L） increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 pmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and ac- tivation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine （50-5000 μmol/L） stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions： Homocysteine （50-1000 μmol/L） significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and acti- vation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.展开更多
基金supported by the Construction of Prevention and Treatment System of Geriatric Syndromes Focusing on Disability and Dementia(No.21-1-2-2-zyyd-nsh)。
文摘Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.
文摘Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detect the expres- sions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE). The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results: The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% (64/72) in group ICC and 12.5% (2/16) in group NCE, P = 0.000; MMP-9: 94.4% (68/72) in group ICC and 43.8% (7/16) in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis (r = 0.296, P = 0.012) and stromal invasion (r = 0.257, P = 0.029). The expression of MMP-9 was positively correlated with FIGO stage (r = 0.329, P = 0.005) and histological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). Conclusion: The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.
文摘Objective:The aim of the study was to investigate the expressions of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of MMP-2(TIMP-2) mRNA in transitional cell carcinomas of bladder and discuss their clinical significances.Methods:Using RT-PCR and real time quantitative PCR(RQ-PCR) technique,the expressions of MMP-2 and TIMP-2 mRNA of 45 cases of bladder carcinoma(tumor group) and 10 cases of normal bladder tissue(control group) were analyzed.Results:MMP-2 and TIMP-2 were not expressed in control group.MMP-2 was expressed in 30 cases tumor samples and TIMP-2 was expressed in 26 cases.The expression of MMP-2 mRNA in non-muscle invasive bladder cancers and grade I cancers was lower than that in muscle invasive bladder cancers and grades II-III cancers respectively.The differences were statistically significant(P<0.05).The expression of MMP-2 in recurrent patients was higher than that in incipient patients.TIMP-2 mRNA expression decreased with grades and stage.The expression of TIMP-2 in non-muscle invasive bladder cancers and grade I cancers was higher than that in muscle invasive bladder cancers and grades II-III cancers respectively.There was statistical difference between two groups(P < 0.05).TIMP-2 expression in incipient patients was higher than that in recurrent patients,but the difference was not significant(P>0.05).Conclusion:These results suggest that MMP-2 and TIMP-2 play an important role in the invasion step of transitional cell carcinoma of bladder.MMP-2 may become a new approach to the diagnosis of bladder carcinoma.
文摘Objective:To investigate the expression and significance of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-13(MMP-13)in bullous pemphigoid(BP)skin lesions.Methods:Immunohistochemical SP method was used to detect the expression of MMP-2 and MMP-13 in 32 BP skin lesions,and compared with 15 normal skin tissues.Results:The expression of MMP-2 in the case group was significantly increased(38.56±10.06)compared to the normal control group(21.20±5.98);the expression of MMP-13 in the case group was significantly augmented(18.62±5.90)compared to the normal control group(11.47±8.484).The expressions of MMP-2 and MMP-13 in the skin lesions of patients with bullous pemphigoid were statistically different from those of normal people(both P<0.05).Compared with the expression of MMP-2 and MMP-13 in bullous pemphigoid,the expression of MMP-2 and MMP-13 was moderately correlated(correlation coefficient was 0.523).Conclusion:The expression of MMP-2 and MMP-13 is significantly increased in bullous pemphigoid skin lesions,suggesting that they may play an important role in the pathogenesis of BP.There is a certain correlation between the expression of MMP-2 and MMP-13,suggesting that the high expression of MMP-13 may play a role in the mechanism that further leads to the high expression of MMP-2.
基金Project supported by the Health Ministry Scientific Research Fund of China (No. WKJ2011-2-018)the Zhejiang Provincial Natural Science Foundation of China (No. Y2100535)+3 种基金the Key Social Development Project of Zhejiang Province (No. 2010A23010)the Science and Technology Projects of Shaoxing (No. 2011A23011)the Science and Technology Plan Project of Zhejiang Province (No. 2012C33040)the Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents, China
文摘Objective： To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 （MMP-2） and tissue inhibitors of matrix metalloproteinase-2 （TIMP-2） and on cell migration of cultured rat vascular smooth muscle cells （VSMCs）. Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods： Rat VSMCs were incubated with different concentrations of homocysteine （50-5000 μmol/L）. Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin （10^-9-10^-5 mol/L） were added when VSMCs were induced with 1 000 pmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results： Homocysteine （50-1000 μmol/L） increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 pmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and ac- tivation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine （50-5000 μmol/L） stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions： Homocysteine （50-1000 μmol/L） significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and acti- vation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.
