脑泰方提取物干预大鼠脑缺血后MMP-9-mRNA及PA-mRNA表达研究

目的研究大鼠脑缺血后益气活血中药脑泰方提取物(黄芪、川芎、地龙、僵蚕)干预对缺血区脑水肿及MMP-9-mRNA、PA-mRNA表达的影响。方法随机将SD大鼠分为假手术组、模型组、脑泰方提取物(NTE)低、中、高剂量组(3,9,27g/kg)。各组大鼠预处理ig给药连续3d,每日1次,MCAO模型制备术后ig给药1d。术后1d取材检测各组脑组织含水量,RT-PCR检测MMP-9-mRNA及PA-mRNA表达。结果实验表明高、中NTE组与模型组比较,脑含水量均有明显降低(P<0.05)。NTE高剂量组脑缺血区MMP-9-mRNA、PA-mRNA表达明显降低(P<0.05)。结论脑泰方提取物干预可减轻脑水肿的发生,可能是通过降低MMP-9-mRNA及PA-mRNA的表达,减少MMP-9、PA的生成,发挥保护急性脑缺血血脑屏障的作用。

Clinicopathological and prognostic role of MMP-9 in esophageal squamous cell carcinoma: a meta-analysis

Objective： Many studies reported that matrix metalloproteinase-9 （MMP-9） participated in the development of esophageal squamous cell carcinoma （ESCC） and resulted in poor prognosis, however, they all included few patients and had inconsistent results. So we conducted a meta-analysis to explore the correlation between overexpression of MMP-9 and the clinicopathological characteristics and overall survival （OS） of ESCC. Methods： PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, Google Scholar and other databases were searched for relevant studies. The Newcastle-Ottawa quality assessment scale was used to assess the methodological quality of included study and RevMan 5.2 software was used to conduct meta-analysis. Results： A total of 35 studies were included, and the results of meta-analysis showed that overexpression of MMP-9 was associated with grade of differentiation [well/moderate vs. poor： odds ratio （OR）： 0.39, 95% confidence interval （CI）： 0.29-0.52; P〈0.00001], lymph node metastasis （negative vs. positive： OR： 0.24, 95% CI： 0.16-0.34; P〈0.00001）, TNM stage （T1/T2 vs. T3/T4： OR： 0.28, 95% CI： 0.14-0.54; P=0.0002）, the depth of invasion （T1/T2 vs. T3/T4： OR： 0.29, 95% CI： 0.17-0.49; P〈0.00001）, and vascular invasion of ESCC （negative vs. positive： OR： 0.35, 95% CI： 0.21-0.58; P〈0.0001）, and also associated with poor overall survival ofESCC （HR： 2.17, 95% CI： 1.32-3.57; P=0.002）. Subgroup analysis showed that more than 10% of carcinoma cell staining was associated with significant increase of mortality risk （HR： 2.44, 95 % CI： 1.16-5.15; P=0.02）, and sensitive analysis suggested that MMP-9 was an independent prognostic factor in ESCC （HR： 1.49, 95% CI： 1.16-1.91; P=0.002）. Conclusions：On the basis of limited evidence, overexpression of MMP-9 may be a potential independent prognosis factor of ESCC patients in Asia, and high-quality studies assessing the prognostic significance of MMP-9 for ESCC patients are still needed.

Multifactor Regulation on Expressions of MMP-9 and TIMP-1 in Endometrial Stromal Cells

Objective To investigate the regulatory effect of multifactor on the matrix metalloproteinases-9 （MMP-9） and the tissue inhibitor of metalloproteinase-1 （TIMP-1） in endometrial stromal cells. Methods The endometrial stromal cells separated from the proliferative endometrial tissues were incubated with medium alone, 17-β estradiol （E2,10^-8 mol/L）, medroxyprogesterone acetate （MPA, 10^-6 mol/L）, E2（10^-8 mol/L）＋MPA （10^-6 mol/L）, E2 （10^-8 mol/L）＋MPA （10^-6 mol/L）＋RU486 （10^-5 mol/L） or HB-EGF （10 ng/ml） for 48 h respectively. The expressions of MMP-9 and TIMP-1 were detected by in situ hybridization, immunocytochemistry, reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blotting. Results Compared with control group [mRNA, 0. 729 ± 0. 090 （MMP-9） and 1.056± 0.154 （TIMP-1）; protein, 0.545 ±0.086 （MMP-9） and 0.745 ±0.154 （TIMP-1）], expressions of MMP-9 and TIMP-1 in E2 alone, progestin alone or E2 combined with progestin group were respectively：mRNA, 0.413 ± 0.069, 0.402 ± 0.073 and 0.407 ± 0.039; 0.487 ± 0.093, 0.503 ± 0.093 and 0.468 ± 0.075：protein, 0.294 ± 0.076, 0.331 ±0.064 and 0.265 ±0.049; 0.425 ±0.085, 0.397 ±0.065 and 0.435 ± 0.099. RU486 weakened the expression level of down-regulation, while HB-EGF elevated the level of MMP-9 and TIMP-1 after 48 h treatment （mRNA, 0.955 ± 0.068 and 1.396 ± 0.238; protein, 0. 780 ± 0.109 and 0.985 ± 0.165）. Conclusions 1） Both E2 and progestin can down-regulate the expressions of MMP-9 and TIMP-1 in endometrial stromal cells, but RU486 can inhibit the effect. 2） HB-EGF can elevate the level of MMP-9 and TIMP-1. 3） E2, progestin and HB-EGF have effect on the ratio of MM-P/TIMP-1.

Association between the-1562 C/T polymorphism in the MMP-9 promoter and phenotype of esophageal squamous cell carcinoma in northern Chinese population

Objective To conduct a case-control study on the association of the nucleotide polymorphisms in the promoter region of the matrix metalloproteinase-9(MMP-9)gene with phenotype of esophageal cancer.Methods All subjects were unrelated residents in northern regions of China.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)analysis was used to determine the MMP-9 genotypes.Results The overall distribution of genotypes in the patients was not different from that in the controls(OR=0.77,95% CI=0.45-1.34;P=0.36).There were no significant differences between the patients and the control subjects in terms of the distributions of sex and age,smoking status,alcohol dependence,pickled diet status,or history of environmental exposure.The patients were further examined with stratifications by age,sex,grade,depth of tumor invasion,lymphatic invasion,venous invasion and TNM staging.The results showed no pronounced association among the stratifications.Conclusion There is no significant association between the MMP-9 single nucleotide polymorphism genotypes and phenotype of esophageal cancer.

Association of Matrix Metalloproteinase-9 and p53 Gene Polymorphisms with Genetic Susceptibility to No-small-cell Lung Cancer

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.

Matrix Metalloproteinase-9 in the Etiopathogenesis of Placenta Accreta Spectrum:A Literature Review

The recent increase in placenta accreta spectrum has been correlated with a rise in the rate of cesarean sections.A recent study provides evidence that hampered wound healing results in cesarean scar defects that lead to a failure in the normal process of decidualization and deeper adherence of trophoblasts.Matrix metalloproteinase(MMP)is crucial in every step of wound healing as it alters the wound matrix,facilitating cell migration,as well as tissue remodeling.MMP-9 expression is higher in placental and decidual tissue in cases of placenta accreta.Based on these findings,assessment of MMP-9 expression can shed new light on the etiopathology of placenta accreta spectrum disorder and can be a potential diagnostic marker.

基质金属蛋白酶-9与肾脏疾病关系的研究进展

基础研究表明，非肿瘤性肾脏疾病的病理改变实质均是细胞外基质（extra cellular matrix，ECM）在肾小球和肾间质中异常堆积的结果。ECM沉积发生机制复杂，其中基质金属蛋白酶（matrix metallo proteinases，MMPs）及其组织抑制因子（tissue inhibitors ofmetalloproteinases，TIMPs）的功能紊乱在ECM转换过程中起关健作用。MMP-9是基质金属蛋白酶家族中的重要成员之一，因其作用底物广泛，表达细胞众多，在国内外研究中备受重视。现将其与肾脏疾病关系的研究进展综述如下。

Ds-echinoside A,a new triterpene glycoside derived from sea cucumber,exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions

Ds-echinoside A (DSEA),a non-sulfated triterpene glycoside,was isolated from the sea cucumber Pearsonothuria graeffei.In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion,migration,invasion,and angiogenesis.In this study,we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2,with a half-maximal inhibitory concentration (IC50) of 2.65 μmol/L,and suppressed Hep G2 cell adhesion,migration,and invasion in a dose-dependent manner.DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo.Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9),which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis.DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1),an important regulator of MMP-9 activation.From the results of Western blotting,the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA.These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.

Higher production of tumor necrosis factor alpha in hemozoin-fed human adherent monocytes is dependent on lipidic component of malarial pigment:new evidences on cytokine regulation in Plasmodium falciparum malaria

Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.