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A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury
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作者 Qi Liu Jianye Xie +5 位作者 Runxue Zhou Jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi 《Neural Regeneration Research》 SCIE CAS 2025年第2期503-517,共15页
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv... Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury. 展开更多
关键词 angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 NEUROPROTECTION self-assembling nanofiber hydrogel
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Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis
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作者 Qiang Zou Hao-Wen Wang +2 位作者 Xi-Liang Di Yuan Li Hui Gao 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第4期1547-1563,共17页
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t... BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression. 展开更多
关键词 Hepatocellular carcinoma Ultrasound microbubbles Long noncoding RNA HAND2-AS1 miR-873-5p Tissue inhibitor of matrix metalloproteinase-2
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Methanol extract of Codium fragile inhibits tumor necrosis factor-ɑ-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation 被引量:1
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作者 Matharage Gayani Dilshara Rajapaksha Gedara Prasad Tharanga Jayasooriya +2 位作者 Chang-Hee Kang Yung-Hyun Choi Gi-Young Kim 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2016年第6期520-525,共6页
Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(... Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(MMP-9).Methods:Reverse transcriptionpolymerase chain reaction(RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB(NF-κB) subunits,p65 and p50,and IκB in MDA-MB-231 cells.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT) assay was used for cell viability.MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay,respectively.NF- κB activity was measured by an electrophoretic mobility shift assay and luciferase activity.Results:MECF had no effects on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α.MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control,whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells.Additionally,zymography,western blot analysis,and reverse transcriptase-polymerase chain reaction(RT-PCR) confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion.According to an electrophoretic morbidity shift assay,pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of nuclear factor- κB(NF- κB),which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9.Furthermore,treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment.The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF- κB luciferase activity.Conclusion:MECF exhibited its antiinvasive capability by downregulating TNF-α-induced MMP-9 expression,resulting from the suppression of NF- κB activity in the human breast cancer cell line MDA-MB-231. 展开更多
关键词 Codium fragile INVASION Nuclear factor-κB matrix metalloproteinase-9 Tumor NECROSIS factor-α
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Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma
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作者 Qiu-Ju Liang Qin-Qin Long +3 位作者 Feng-Qin Tian Qun-Ying Su Xiao-Ying Zhu Xi-Dai Long 《World Journal of Hepatology》 2024年第8期1131-1144,共14页
BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associa... BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC. 展开更多
关键词 Tissue inhibitor of metalloproteinase-3 expression Aflatoxin B1 Hepatocellular carcinoma Clinicopathological feature PROGNOSIS
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Association of Matrix Metalloproteinase-9 and p53 Gene Polymorphisms with Genetic Susceptibility to No-small-cell Lung Cancer
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作者 ZHAO Ying-hao MA Tong-hui +5 位作者 ZHENG Yong-chen ZHANG Kun YANG Jing-bo YANG Long-fei YANG Zhi-guang SHAO Guo-guang 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2011年第1期80-82,共3页
Matrix metalloproteinase-9(MMP-9) and p53 genes play an essential role in the multi-step process of tumorigenesis in lung cancer. Single nucleotide polymorphisms(SNPs) of MMP-9 and p53 genes are associated with th... Matrix metalloproteinase-9(MMP-9) and p53 genes play an essential role in the multi-step process of tumorigenesis in lung cancer. Single nucleotide polymorphisms(SNPs) of MMP-9 and p53 genes are associated with the risk and progression of many cancers. In this study, we evaluated the association of the R279Q polymorphism of MMP-9 or the A1/A2 polymorphism of p53 gcne with the risk of no-small-cell lung cancer(NSCLC) in Han population of Northeast China. We examined the frequency of SNPs in the two kinds of genes of 50 patients with NSCLC and 50 cancer-free controls frequency-matched by age and sex. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique was used to determine the genotypes. The results indicate that the 279RR genotype in MMP-9 gene and the A1/A2 genotype in p53 gene show a significantly increased risk of NSCLC. Therefore, the MMP-9 279RR and p53 A1/A2 genotypes may be used as markers for susceptibility to NSCLC in Han population of Northeast China. 展开更多
关键词 Single nucleotide polymorphisms(SNPs) No-small-cell lung cancer(NSCLC) matrix metalloproteinase-9(MMP-9) p53 SUSCEPTIBILITY
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Error modeling of 3-RSR parallel robot based on D-H transformation matrix 被引量:3
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作者 李瑞琴 杨斌 《Journal of Measurement Science and Instrumentation》 CAS 2014年第3期53-59,2,共7页
By selecting any one limb of 3-RSR parallel robot as a research object, the paper establishes a position and orienta- tion relationship matrix between the moving platform and the base by means of Denavit-Hartenberg (... By selecting any one limb of 3-RSR parallel robot as a research object, the paper establishes a position and orienta- tion relationship matrix between the moving platform and the base by means of Denavit-Hartenberg (D-H) transformation matrix. The error mapping model is derived from original error to the error of the platform by using matrix differential method. This model contains all geometric original errors of the robot. The nonlinear implicit function relation between po- sition and orientation error of the platform and the original geometric errors is simplified as a linear explicit function rela- tion. The results provide a basis for further studying error analysis and error compensation. 展开更多
关键词 error modeling 3-RSR parallel robot Denavit-Hartenberg (D-H) transformation matrix
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乳腺癌组织中TIMP-3及DNMT1的表达与患者预后的相关性
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作者 于娇 李汉杰 +3 位作者 陈鑫 王青 葛鹏 李刚 《现代肿瘤医学》 CAS 2024年第17期3248-3253,共6页
目的:分析研究乳腺癌患者中基质金属蛋白酶组织抑制因子3(TIMP-3)及DNA甲基转移酶1(DNMT1)的表达水平与患者临床预后的相关性。方法:收集58例临床资料完整的乳腺癌手术切除标本,采用免疫组化SP法检测癌组织及相应癌旁组织中TIMP-3、DNMT... 目的:分析研究乳腺癌患者中基质金属蛋白酶组织抑制因子3(TIMP-3)及DNA甲基转移酶1(DNMT1)的表达水平与患者临床预后的相关性。方法:收集58例临床资料完整的乳腺癌手术切除标本,采用免疫组化SP法检测癌组织及相应癌旁组织中TIMP-3、DNMT1、ER、PR、HER-2、p53、Ki-67的表达,将TIMP-3、DNMT1表达水平与临床病理参数及随访生存状况进行相关性分析,所有入组患者均进行随访5年以上。结果:我们发现,在乳腺癌组织中,TIMP-3呈低表达,DNMT1呈高表达,TIMP-3及DNMT1的表达呈负相关;TIMP-3表达水平与Ki-67呈负相关,DNMT1表达水平与Ki-67呈正相关,与其他临床病理参数未见相关性。Cox风险比例模型分析显示只有临床分期和DNMT1表达水平是影响总生存期(OS)和无病生存期(DFS)的独立风险因素。TIMP-3低表达组的5年OS和DFS均显著低于高表达组,DNMT1高表达组的5年OS和DFS均显著低于低表达组。结论:研究表明乳腺癌中TIMP-3及DNMT1表达水平与肿瘤细胞恶性表型及患者生存时间有关,可能成为判断乳腺癌预后的一项重要指标,并作为治疗计划制定的依据。 展开更多
关键词 乳腺癌 基质金属蛋白酶组织抑制因子3 DNA甲基转移酶1 总生存期 无病生存期
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类风湿关节炎患者血清SAA、CCL20、MMP-3表达水平及临床意义
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作者 霍月红 郭燕羽 王贯虹 《临床和实验医学杂志》 2024年第5期497-501,共5页
目的探讨类风湿关节炎(RA)患者血清淀粉样蛋白A(SAA)、趋化因子配体20(CCL20)及基质金属蛋白酶3(MMP-3)水平变化及临床意义。方法回顾性选取2020年9月至2023年1月大同市第五人民医院收治的RA患者108例作为研究对象,依据28个关节的疾病... 目的探讨类风湿关节炎(RA)患者血清淀粉样蛋白A(SAA)、趋化因子配体20(CCL20)及基质金属蛋白酶3(MMP-3)水平变化及临床意义。方法回顾性选取2020年9月至2023年1月大同市第五人民医院收治的RA患者108例作为研究对象,依据28个关节的疾病活动度评分(DAS28)评分,将患者分为缓解期组(n=35,DSA28评分<2.6)与活动期组(n=73,DSA28评分≥2.6),并将活动期患者进一步分为轻度活动期(n=20,DSA28评分2.6~3.2)、中度活动期(n=29,DSA28评分>3.2~5.1)与重度活动期(n=24,DSA28为>5.1);另选取同期健康体检者80名作为对照组。所有受试者均检测血清SAA、CCL20、MMP-3水平。比较不同组别血清SAA、CCL20、MMP-3水平;使用Pearson相关分析血清SAA、CCL20、MMP-3水平与红细胞沉降率(ESR)、C反应蛋白(CRP)的相关性;使用受试者工作特征(ROC)曲线评价各指标对RA疾病活动度的诊断价值。结果RA组血清SAA、CCL20、MMP-3水平分别为(42.25±13.46)mg/L、(45.69±12.78)pg/mL、(85.41±25.14)ng/mL,均显著高于对照组[(7.14±2.12)mg/L、(18.12±5.47)pg/mL、(27.36±8.21)ng/mL],差异均有统计学意义(P<0.05)。RA活动期组患者血清SAA、CCL20、MMP-3水平分别为(51.78±10.71)mg/L、(53.14±10.45)pg/mL、(106.10±20.39)ng/mL,显著高于缓解期组[(22.37±7.14)mg/L、(30.15±8.24)pg/mL、(42.25±13.64)ng/mL],差异均有统计学意义(P<0.05)。重度活动度组血清SAA、CCL20、MMP-3水平均高于中度活动度组和轻度活动度组,差异均有统计学意义(P<0.05),随着疾病活动度提高,血清SAA、CCL20、MMP-3水平逐渐增高。Pearson相关分析显示,活动期RA患者血清SAA、CCL20、MMP-3水平与CRP、ESR均呈正相关(P<0.05)。ROC曲线分析得出,血清SAA、CCL20、MMP-3区分RA轻度活动度与中度活动度的曲线下面积(AUC)分别为0.852、0.756、0.725,区分中度活动度与重度活动度的AUC分别为0.852、0.756、0.725,均显示出一定的诊断能力。结论RA患者血清SAA、CCL20、MMP-3水平均呈高表达,这3项指标可作为评估疾病活动度的生物标志物,可为临床预测病情进展提供参考。 展开更多
关键词 类风湿关节炎 疾病活动度 淀粉样蛋白A 趋化因子配体20 基质金属蛋白酶3
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慢性肾脏病患者血清CHI3L1、MMP-13表达水平及其病情评估、预后价值
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作者 唐方平 刘义强 +1 位作者 李娜 付平 《国际检验医学杂志》 CAS 2024年第9期1101-1105,共5页
目的探讨慢性肾脏病患者血清几丁质酶3样蛋白1(CHI3L1)、基质金属蛋白酶-13(MMP-13)表达水平及病情评估、预后价值。方法选取2020年3月至2022年8月在江油市人民医院就诊的208例慢性肾脏病患者作为病例组,按照病情严重程度将208例慢性肾... 目的探讨慢性肾脏病患者血清几丁质酶3样蛋白1(CHI3L1)、基质金属蛋白酶-13(MMP-13)表达水平及病情评估、预后价值。方法选取2020年3月至2022年8月在江油市人民医院就诊的208例慢性肾脏病患者作为病例组,按照病情严重程度将208例慢性肾脏病患者分为Ⅰ期组21例、Ⅱ期组42例、Ⅲ期组86例、Ⅳ期组38例、Ⅴ期组21例。另选取同期152例体检健康者作为对照组。根据患者预后情况将208例患者分为预后良好组(n=92)及预后不良组(n=116)。收集受试人员一般资料,采用酶联免疫吸附试验检测血清CHI3L1、MMP-13表达水平,Pearson法分析慢性肾脏病患者血清CHI3L1、MMP-13表达水平的相关性,以及二者与肾小球滤过率(GFR)的相关性,采用Cox回归分析影响慢性肾脏病患者预后的因素。结果对照组、病例组年龄、性别等一般资料比较,差异无统计学意义(P>0.05);病例组患者血清中CHI3L1表达水平较对照组显著增加,但MMP-13表达水平显著降低,差异有统计学意义(P<0.05);随着病情分期增加,患者血清CHI3L1表达水平随之增加,MMP-13表达水平随之降低(P<0.05);预后不良组患者血清CHI3L1表达水平较预后良好组显著增加,MMP-13表达水平显著降低(P<0.05);Pearson法分析显示,慢性肾脏病患者血清CHI3L1、MMP-13表达水平呈负相关,CHI3L1表达水平与GFR呈负相关,MMP-13表达水平与GFR呈正相关(P<0.05)。Cox回归分析显示,血清CHI3L1、MMP-13、GFR为慢性肾脏病患者预后不良的独立影响因素(P<0.05)。结论慢性肾脏病患者血清CHI3L1表达水平升高,MMP-13表达水平降低,二者均可用于病情及预后评估。 展开更多
关键词 慢性肾脏病 几丁质酶3样蛋白1 基质金属蛋白酶-13
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Study on the expression of matrix metalloproteinase-2 mRNA in human gastric cancer 被引量:19
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作者 Ji F Wang WL +3 位作者 Yang ZL Li YM Huang HD Chen WD 《World Journal of Gastroenterology》 SCIE CAS CSCD 1999年第5期455-457,共3页
关键词 matrix metalloproteinase-2 MRNA STOMACH ncoplasms POLYMERASE CHAIN REACTION
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Levels of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 in gastric cancer 被引量:10
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作者 Ozgur Kemik Ahu Sarbay Kemik +9 位作者 Aziz Sümer Ahmet Cumhur Dulger Mine Adas Huseyin Begenik Ismail Hasirci Ozkan Yilmaz Sevim Purisa Erol Kisli Sefa Tuzun Cetin Kotan 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第16期2109-2112,共4页
AIM:To evaluate the levels of preoperative serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in gastric cancer.METHODS:One hundred gastric cancer patients who underwent gast... AIM:To evaluate the levels of preoperative serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in gastric cancer.METHODS:One hundred gastric cancer patients who underwent gastrectomy were enrolled in this study.The serum concentrations of MMP-1 and TIMP-1 in these patients and in fifty healthy controls were determined using an enzyme-linked immunosorbent assay.RESULTS:Higher serum MMP-1 and TIMP-1 levels were observed in patients than in controls (P < 0.001).Serum MMP-1 and TIMP-1 levels were positively associated with morphological appearance,tumor size,depth of wall invasion,lymph node metastasis,liver metastasis,perineural invasion,and pathological stage.They were not significantly associated with age,gender,tumor location,or histological type.CONCLUSION:Increased MMP-1 and TIMP-1 were associated with gastric cancer.Although these markers are not good markers for diagnosis,these markers show in advanced gastric cancer. 展开更多
关键词 Gastric cancer matrix metalloproteinase-1 Tissue matrix metalloproteinase-1
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Clinical significance of matrix metalloproteinase-9 expression in esophageal squamous cell carcinoma 被引量:18
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作者 Zhen-DongGu Ke-NengChen +2 位作者 MingLi JinGu Ji-YouLi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第6期871-874,共4页
AIM: To evaluate the expression of matrix metalloproteinase-9 (MMP-9) and its clinical significance in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of MMP-9 in 208 cases of ESCC was detected by i... AIM: To evaluate the expression of matrix metalloproteinase-9 (MMP-9) and its clinical significance in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of MMP-9 in 208 cases of ESCC was detected by immunohistochemistry (IHC) and its clinical significance in ESCC especially the relationship with the clinicopathological parameters was analyzed. RESULTS: The percentage of positive cases for MMP-9 detected by IHC was 49.0%. MMP-9 was mainly expressed in the cytoplasm of cancer cells especially in the invasive front. Only weak expression was detected in the stromal cells and no expression in non-cancerous mucosa. The expression of MMP-9 was positively correlated with poorer differentiation (P= 0.001<0.01), existence of vessel permeation (P= 0.027<0.05) and lymph node metastasis (P=0.027<0.05). CONCLUSION: The expression of MMP-9 correlates with the cancer cell differentiation, vessel permeation and lymph node metastasis. It may be a novel biomarker for the diagnosis and treatment of ESCC. 展开更多
关键词 matrix metalloproteinase-9 Esophageal squamous cell carcinoma IMMUNOHISTOCHEMISTRY Clinicopathological parameters BIOMARKER
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Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in ulcerative colitis 被引量:13
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作者 Ying-De Wang Pei-Yun Yan 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第37期6050-6053,共4页
AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polym... AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC. 展开更多
关键词 matrix metalloproteinase-1 Tissue inhibitor of metalloproteinase-1 Ulcerative colitis Reverse transcriptionpolymerase chain reaction IMMUNOHISTOCHEMISTRY
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Suppression of matrix metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and adhesion 被引量:16
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作者 Ying-Hui Zhi Mao-Min Song Pi-Lin Wang Tie Zhang Zi-Yi Yin 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第9期1072-1078,共7页
AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was ... AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line,BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1,pGPU6-2,pGPU6-3 and pGPU6-4,and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry,respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers.RESULTS:The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect,followed by pGPU6-2 and pGPU6-3 groups.Invasiveness and adhesion were more significantly reduced in pGPU6-1,pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However,no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups.CONCLUSION:RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line,BxPC-3,leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor. 展开更多
关键词 Pancreatic neoplasm Tumor metastasis matrix metalloproteinase-2 Small interfering RNA Tumor invasiveness
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Matrix metalloproteinase-9-1562C>T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer 被引量:12
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作者 Li-Li Xing Zhen-Ning Wang +5 位作者 Li Jiang Yong Zhang Ying-Ying Xu Juan Li Yang Luo Xue Zhang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第34期4626-4629,共4页
AIM. To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population.METHODS: Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was car... AIM. To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population.METHODS: Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).RESULTS: The distribution of IVllVlP-9 -2562C〉T and 279 R〉Q genotype was not significantly associated with the risk of CRC. However, the risk of Ilymph node metastasis of CRC was increased in patients with the -1562T allele (OR = 2.601; 95% CI = 1.160-5.835; P = 0.022). The frequency of MMP-9 279RR + RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old (OR = 0.102, 95% CI = 0.013-0.812; P = 0.012).CONCLUSION: Our results indicated that the MMP-9- 1562C〉T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer. 展开更多
关键词 matrix metalloproteinase-9 POLYMORPHISMS Colorectal cancer Lymphatic node metastasis
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Picroside Ⅱ down-regulates matrix metalloproteinase-9 expression following cerebral ischemia/reperfusion injury in rats 被引量:13
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作者 Xiang Li Xinying Xu +4 位作者 Zhen Li Yunliang Guo Qin Li Xiaodan Li Zhen Zhou 《Neural Regeneration Research》 SCIE CAS CSCD 2010年第18期1403-1407,共5页
Studies have shown that Picroside Ⅱ attenuates inflammatory reactions following brain ischemia through the inhibition of the TLR-4-NF-KB signal transduction pathway, and ameliorates cerebral edema through the reducti... Studies have shown that Picroside Ⅱ attenuates inflammatory reactions following brain ischemia through the inhibition of the TLR-4-NF-KB signal transduction pathway, and ameliorates cerebral edema through the reduction of aquaporin-4 expression. Matrix metalloproteinase-9 (MMP-9), located downstream of the TLR-4-NF-KB signal transduction pathway, can degrade the neurovascular matrix, damage the blood-brain barrier to induce cerebral edema, and directly result in neuronal apoptosis and brain injury, Therefore, the present study further observed MMP-9 expression in the brain tissues of rats with cerebral ischemia/reperfusion injury following Picroside Ⅱ treatment. Results demonstrated that Picroside Ⅱ significantly reduced MMP-9 expression in ischemic brain tissues, as well as neuronal apoptosis and brain infarct volume, suggesting Picroside Ⅱ exhibits neuroprotection by down-regulating MMP-9 expression and inhibiting cell apoptosis. 展开更多
关键词 Picroside cerebral ischemia/reperfusion injury APOPTOSIS matrix metalloproteinase-9 RATS neural regeneration
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Expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in brain tissue of diabetic rats with ischemia reperfusion 被引量:9
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作者 Yu-Zhi Liang Zhi-Lei Zeng +3 位作者 Lin-Lin Hua Jin-Feng Li Yun-Liang Wang Xi-Zhuang Bi 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2016年第6期568-572,共5页
Objective: To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. Methods: A total ... Objective: To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. Methods: A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor(VEGF) and matrix metalloproteinase-9(MMP-9) in the brain tissue. Results: The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group(P<0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group(P<0.05). MMP-9 began to be be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly higher than that in the single cerebral infarction group(P<0.05). Conclusions: The high glucose environment in which the diabetic cerebral infarction is occurred is to induce the formation of MMP-9 at first and then activate and increase the expression of angiostatin. Afterwards, the expression of VEGF is inhibited, resulting in the poor angiogenesis after cerebral infarction, which thus makes the injury of brain tissue after cerebral infarction even worse than the non-diabetes mellitus. 展开更多
关键词 ANGIOSTATIN Vascular ENDOTHELIAL growth factor matrix metalloproteinase-9 Diabetes MELLITUS Cerebral INFARCTION Ischemia REPERFUSION
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Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer 被引量:12
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作者 FengJi Yue-LiangChen En-YunJin Wei-LinWang Zi-LiYang You-MingLi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第21期3222-3226,共5页
AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric canc... AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer. METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RT-PCR and Northern blot respectively.Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA,uPA and uPA-R mRNA in tumor tissues (31%,41%,and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; X2=4.59,43.58, and 53.24 respectively, P<0.05,0.0001,and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis: 61.9%, no metastasis: 39.1%, X2= 7.61, P<0.05),Lauren's classification of diffuse/mixed types:54.2%,intestinal type: 26.3%,X2 = 4.25, P<0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, X2=5.72 and 6.40 respectively, P<0.05).Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P= 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer. 展开更多
关键词 Gastric cancer matrix metalloproteinase-2 Urokinase-type plasminogen activator
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Correlation of RECK with Matrix Metalloproteinase-2 in Regulation of Trophoblast Invasion of Early Pregnancy 被引量:6
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作者 郭君红 邹丽 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2006年第6期738-740,共3页
To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene and matrix metalloproteinase-2 (MMP-2) in the regulation of trophoblast invasion of early pregnancy. Immunohistochemi... To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene and matrix metalloproteinase-2 (MMP-2) in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women (27 in the early pregnancy, 25 in the term pregnancy). Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group (P〈0.05). RECK expression was significantly lower in cellular column (CC) with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy (P〈0.05). The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35±0.14 and 2.68±0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time (P〈0.01). The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46±0.05 and 0.10±0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy. 展开更多
关键词 RECK matrix metalloproteinase-2 PLACENTA INVASION
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High matrix metalloproteinase-9 expression induces angiogenesis and basement membrane degradation in stroke-prone spontaneously hypertensive rats after cerebral infarction 被引量:30
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作者 Huilian Hou Guanjun Zhang +3 位作者 Hongyan Wang Huilin Gong Chunbao Wang Xuebin Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2014年第11期1154-1162,共9页
Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly underst... Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke- prone spontaneously hypertensive rats by intragastric administration of high-sodium water (1.3% NaC1) for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone sponta- neously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregula- tion is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodi- um water-induced focal cerebral infarction. 展开更多
关键词 nerve regeneration cerebral infarction matrix metalloproteinase-9 collagen IV microvessel density ANGIOGENESIS basement membrane degradation high sodium stroke-pronespontaneously hypertensive China Medical Board Project neural regeneration
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