The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas.We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean ± standard deviation because of the difference in the detection method.Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61-11.50, P < 0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91-3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63-7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52-6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06-2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48-2.20, P = 0.95).The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further.

Previous studies have yielded controversial results related to the contribution of matrix metalloproteinase-2 (MMP-2) -1306 C/T and -735 C/T polymorphisms in the progression of coronary artery disease (CAD). This study aimed to provide strong evidence for the role of the 2 polymorphisms in genetic risk of CAD.The human case-control studies regarding the association of MMP-2 polymorphisms with CAD risk were systematically identified through online databases (PubMed, Embase, the Cochrane Library, and CNKI) and manual search. Inclusion criteria were defined for the eligible studies. The fixed-effects meta-analysis was performed to combine the values when homogeneity was indicated. Alternatively, the random-effects meta-analysis was utilized.A total of 2118 samples were analyzed in the meta-analysis of -1306 C/T. The odds ratio for the initially tested genetic model was 0.93 (95% confidence interval: 0.78-1.10 under TT + CT vs CC). The remaining comparisons similarly showed -1306 C/T genotypes were not significantly associated with the risk of CAD. We noted the same trend when data were retrained to myocardial infarction studies. Meta-analysis of -735 C/T suggested no clear association with the development of CAD.The results of the current work fail to support a significant involvement of MMP-2 -1306 C/T and -735 C/T polymorphisms in the risk of developing CAD.

Ischemic stroke is a complex vascular disease, which has become 1 of the major causes of morbidity and mortality worldwide. More and more data showed that matrix metalloproteinases (MMPs), in particular, MMP-2 are deleterious after ischaemic stroke. This study investigated the relationship between MMP-2 and stroke risk in the Southern Chinese population.We evaluated single nucleotide polymorphisms (SNP) of MMP-2 in stroke patients in an association study using a case-control design. Six SNPs of MMP2 were selected and genotyped by Agena MassARRAY. SNPStats, Haploview was used to analyze genetic data.Two SNPs in the MMP-2 gene were significantly associated with stroke risk.For rs1132896 (C versus G allele), the C allele was significantly reduced stroke risk (OR = 0.56, 95% confidence intervals [95% CI] = 0.39-0.81, P = .002). The effect of the T allele of rs243849 was IS risk according to an additive genetic model (OR = 0.67, 95% CI = 0.47-0.96, P = .028). We did not found any strong linkage between the six SNPs (rs1132896, rs1053605, rs243849, rs243847, rs243832, rs7201)The results presented strongly indicate that MMP-2 genetic variants are an important mediator of stroke risk.

Matrix metalloproteinase-2 (MMP-2), a member of the zinc-dependent metalloproteinase gene family, plays a vital role in cancer invasion, metastasis, and progression. This systematic review and meta-analysis aims to explore the clinical significance of MMP-2 expression in endometrial cancer.

Matrix metalloproteinase 9 (MMP9), a zinc ion-dependent endopeptidase, is one of the most complex matrix metalloproteinases in the gelatinase family. During tissue remodeling, MMP9 leads to gelatin and collagen degradation, which in turn promotes tumor invasion and metastasis. However, comprehensive pan-cancer analysis has not been performed for MMP9. In addition, the diagnostic and prognostic value of MMP9 as a cancer biomarker remain poorly understood, as well as the utility of MMP9 expression as a predictor of immunological responses. Based on a comprehensive analysis of bioinformatics information, we investigated MMP9 expression in different cancers, correlations between MMP9 expression and cancer prognosis and gene mutations, and relationships between MMP9 expression and immune cell infiltration. Our results indicated that MMP9 was highly expressed in most malignant cancers. MMP9 expression was significantly positively or negatively associated with the clinical prognoses of patients with different kinds of cancer. Furthermore, MMP9 expression significantly correlated with infiltrating cells and the expression levels of immune checkpoint genes. This pan-cancer analysis provides comprehensive information on the potential value of MMP9 as a theranostic biomarker.

We evaluated seizure profile, Toll-like receptor (TLR)-4 polymorphisms, and serum matrix metalloproteinases (MMPs) in patients with calcified neurocysticercosis.One-hundred nine patients with calcified neurocysticercosis with newly diagnosed seizures and 109 control subjects were enrolled. TLR-4 Asp299Gly and Thr399Ile polymorphisms and serum MMP-9 levels were evaluated. The patients were followed for 1 year.Asp/Gly (P = 0.012) and Thr/Ile (P = 0.002), Gly (Asp/Gly plus Gly/Gly) (P = 0.008) and Ile (Thr/Ile plus Ile/Ile) (P = 0.003) genotypes were significantly associated with calcified neurocysticercosis compared with controls. Gly/Gly and Ile/Ile genotypes were not significantly associated (P = 0.529 for Gly/Gly, P = 0.798 for Ile/Ile) with either group. The levels of MMP-9 were higher in calcified neurocysticercosis (P =  < 0.001). The levels of MMP-9 were higher in patients with multiple calcified neurocysticercosis compared with single calcified neurocysticercosis (P =  < 0.001).Headache (P = 0.031), status epilepticus (P = 0.029), Todd paralysis (P = 0.039), lesion size >10 mm (P = 0.001), and perilesional edema (P =  < 0.001) were significantly associated with seizure recurrence. Heterozygous form Asp/Gly (P =  < 0.001) and heterozygous form Thr/Ile (P =  < 0.001) were significantly associated with seizure recurrence. The Gly (Asp/Gly plus Gly/Gly) (P =  < 0.001) and Ile (Thr/Ile plus Ile/Ile) (P =  < 0.001) genotypes were also significantly associated with seizure recurrence. Higher serum MMP-9 levels were significantly associated with seizure recurrence (P =  < 0.001).The TLR-4 gene abnormalities may trigger inflammation around calcified neurocysticercosis leading to an increase in perilesional edema and provocation of seizures.

Gestational trophoblastic diseases (GTDs) are characterized by vascular abnormalities of the trophoblast, but their pathogenesis is unknown. Angiogenin (ANG) and matrix metalloproteinase (MMP)-2, which are molecules implicated in the angiogenic process, may play some role in this process.

Matrix metalloproteinase-2 (MMP-2) polymorphisms have been considered as risk factors of cataracts, but the results still remain controversial. In this study, we have performed a systematic meta-analysis to evaluate the association between MMP-2 polymorphisms and cataract risks.

The current methods of monitoring the activity of lupus nephritis (LN) may cause unnecessary hospital visits or delayed immunosuppressive therapy. We aimed to find a urinary biomarker that could be developed as a home-based test for monitoring the activity of LN.Urine samples were collected immediately before a renal biopsy from patients of suspected active LN, and also from patients with inactive LN, systemic lupus erythematous without LN or healthy controls. Biomarker search was conducted on a cytokine antibody array and confirmation was done by quantitative evaluation with enzyme-linked immunosorbent assay. The Mann-Whiney test or Student t test was used to compare the levels of 9 cytokines between different groups. The sensitivity and specificity of each cytokine for diagnosis of LN was evaluated by receiver operating characteristic curve. A rapid test based on colloidal gold immunochromatography was then developed for bedside or home use. Furthermore, an experimental e-healthcare system was constructed for recording and sharing the results of the rapid test a cloud-assisted internet of things (IoT) consisting of a sensing device, an IoT device and a cloud server.Adiponectin (Acrp30), soluble intercellular cell adhesion molecule-1 (sICAM-1), neural cell adhesion molecule 1 (NCAM-1), and CD26 were significantly higher in urine samples of active LN patients. sICAM-1 appeared more sensitive and specific among these candidates. When the cut-off value of sICAM-1 was set at 1.44 ng/mL, the sensitivity reached 98.33% with a specificity at 85.71%. The sICAM-1 strip test showed comparable sensitivity of 95% and a specificity of 83.3% for assessing the LN activity. Meanwhile, the e-healthcare system was able to conveniently digitize and share the sICAM-1 rapid test results.sICAM-1 appeared to be an excellent biomarker for monitoring LN activity. The e-healthcare system with cloud-assisted IoT could assist the digitalization and sharing of the bedside or home-based sICAM-1 test results.

Both dermatopathic lymphadenopathy (DL) and immunoglobulin G4-related disease (IgG4-RD) are frequently complicated with allergic diseases. However, the relationship between DL and IgG4-RD is not well known. To clarify this relationship on the basis of clinical and pathological findings, including IgG4-positive (IgG4+) plasma cell infiltration in lymph nodes (LNs) of DL patients, we analyzed LNs of 11 DL patients using immunostaining of IgG, IgG4, forkhead box P3 (FOXP3), transforming growth factor (TGF)-β, interferon (IFN)-γ, and matrix metalloproteinase (MMP)-1, MMP-8, and MMP-13. Toluidine blue staining was also performed to identify mast cells. Of 3 patients with a high ratio of IgG4+/IgG+ cells (>40%) and elevated serum IgG4 levels, 2 developed IgG4-RD, whereas the other patient did not. Of 8 patients with a low ratio of IgG4+/IgG+ cells (<40%) or no infiltration of IgG4+ cells, 5 who could be followed did not develop IgG4-RD. The numbers of mast cells were similar to those of TGF-β-positive cells, and serial sections showed that mast cells possibly produce TGF-β. LNs of DL patients with a high ratio of IgG4+/IgG+ cells had significantly more mast cells and TGF-β-positive cells than those of patients with a low ratio of IgG4+/IgG+ cells or no infiltration of IgG4+ cells. However, no fibrosis was observed in LNs of both groups. IFN-γ was positive in interdigitating dendritic cells, Langerhans cells, and macrophages. MMP-1, MMP-8, or MMP-13 was expressed in macrophages. The lack of fibrosis in LNs may have been due to the production of IFN-γ, MMP-1, MMP-8, or MMP-13. Thus, DL with increased IgG4+ cells seems to be a phenotype of IgG4-RD in LNs.

This study aimed to reveal the genetic association between polymorphisms in promoter region of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) and the risk of recurrent spontaneous abortion (RSA) in Chinese population.A total of 129 RSA patients and 116 relative controls were selected and the genotyping of polymorphism was conducted by polymerase chain reaction with sequencing. Genotype distribution of polymorphism in the control group was tested the status of Hardy-Weinberg equilibrium and then, genotype frequencies were compared between the case and control groups by chi-squared test. Odds ratio (OR) with the corresponding 95% confidence interval (95% CI) was computed to express the risk of RSA caused by polymorphism. Moreover, the linkage disequilibrium of polymorphisms in MMP2 was analyzed by Haploview software.CT genotype and T allele of rs243865 in MMP2 were significantly associated with the increased susceptibility to RSA in Chinese population (CT vs. CC: OR = 1.926, 95% CI = 1.101-3.368; T vs. C: OR = 1.751, 95% CI = 1.146-2.676). Similarly, CT genotype carriers of rs3918242 in MMP9 were obviously more in RSA patients than that of the controls (P = .037), which indicated it was associated with the risk of RSA occurrence (OR = 1.760, 95% CI = 1.034-2.995). So was T allele in RSA development (OR = 1.595, 95% CI = 1.061-2.398). Haplotypes C-T and T-C were also the risk factors of RSA (OR = 1.673, 95% CI = 1.103-2.536; OR = 2.171, 95% CI = 1.372-2.436).MMP2 rs243865 and MMP9 rs3918242 polymorphisms are significantly associated with the risk of RSA in Chinese population.

The proportion of alcohol-induced osteonecrosis of the femoral head (ONFH) in all ONFH patients was 30.7%, with males prevailing among the ONFH patients in mainland China (70.1%). Matrix metalloproteinase 2 (MMP2), a member of the MMP gene family, encodes the enzyme MMP2, which can promote osteoclast migration, attachment, and bone matrix degradation. In this case-control study, we aimed to investigate the association between MMP2 and the alcohol-induced ONFH in Chinese males.In total, 299 patients with alcohol-induced ONFH and 396 healthy controls were recruited for a case-control association study. Five single-nucleotide polymorphisms within the MMP2 locus were genotyped and examined for their correlation with the risk of alcohol-induced ONFH and treatment response using Pearson χ test and unconditional logistic regression analysis. We identified 3 risk alleles for carriers: the allele "T" of rs243849 increased the risk of alcohol-induced ONFH in the allele model, the log-additive model without adjustment, and the log-additive model with adjustment for age. Conversely, the genotypes "CC" in rs7201 and "CC" in rs243832 decreased the risk of alcohol-induced ONFH, as revealed by the recessive model. After the Bonferroni multiple adjustment, no significant association was found. Furthermore, the haplotype analysis showed that the "TT" haplotype of MMP2 was more frequent among patients with alcohol-induced ONFH by unconditional logistic regression analysis adjusted for age.In conclusion, there may be an association between MMP2 and the risk of alcohol-induced ONFH in North-Chinese males. However, studies on larger populations are needed to confirm this hypothesis; these data may provide a theoretical foundation for future studies.

Genetic and non-genetic predictors of 15-year survival in patients with chronic three-vessel disease (3VD) were investigated. Coronary angiography was performed on 810 subjects with symptoms of stable ischemic heart disease in 1998. The patients with 3VD were genotyped for 23 candidate polymorphisms covering the PPAR-RXR pathway, matrix metalloproteinase-2, renin-angiotensin-aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Fifteen-year survival data were obtained from the national insurance registry. All data were available in the case of 150 patients with 3VD. Statistical analysis used stepwise Cox regression with dominant, recessive, or additive mode of genetic expression. Involved variables included age, sex, BMI, blood pressure, diabetes, ejection fraction, left main stenosis, previously diagnosed coronary stenosis, myocardial infarction in personal history, and coronary bypass along with polymorphisms pre-selected by log-rank tests. Out of the 23 polymorphisms, four were included in the model construction. SNP in the IL-6 gene rs1800795 (-174 G/C) has been found to be a significant predictor of survival. This SNP was in a linkage disequilibrium with rs1800797 (-597 G/A) in the same gene (D'=1.0), which was also found to constitute a significant predictor of survival when rs1800795 was not included in the model construction. Age, increased BMI, diabetes, low EF, and left main stenosis were also significant predictors in all models. Age, increased BMI, diabetes, low ejection fraction, left main stenosis, and genetic variation in the IL-6 promoter were established as significant independent risk factors for the survival of patients with three-vessel disease.

Osteoarthritis (OA), also known as degenerative arthritis, affects millions of people all over the world. OA occurs when the cartilage wears down over time, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental chondrogenesis as well as to explore potential molecular mechanisms.The expression profiles of GSE51812 were downloaded from the Gene Expression Omnibus (GEO) database, which contained 9 samples, including 6-week pre-chondrocytes (PC, 6 independent specimens) and 17-week fetal periarticular resting chondrocytes (RC, 3 independent specimens). The raw data were integrated to obtain differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. The Gene Ontology (GO) and pathway enrichment of DEGs were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein interaction (PPI) networks of the DEGs were constructed based on data from the search tool for the retrieval of interacting genes (STRING) database. An intersection figure was provided to show the relationship between the DEGs identified in this study and genes from any existed related studies.A total of 9486 DEGs, including 4821 upregulated genes and 4665 downregulated genes were observed. The top 30 developmental chondrogenesis associated genes were identified, including matrix metalloproteinase (MMP)1, MMP3, MMP13, prostaglandin-endoperoxide synthase 2 (PTGS2), and so on. The majority of DEGs, including PTGS2, CCL20, CHI3L1, LIF, CXCL8, and CXCL12 were intensively enriched in immune-associated biological process terms, including inflammatory, and immune responses. Additionally, the majority of DEGs were mainly enriched in NF-kappa β (NF-kβ) signaling pathway and tumor necrosis factor (TNF) signaling pathway. The hub genes identified in STRING and Cytoscape databases included MMP1, MMP3, MMP13, PTGS2 and so on. Among the top 30 upregulated and downregulated DEGs, there were 15 genes have been reported to be associated with OA or developmental chondrogenesis.This large scale gene expression study observed genes associated with human developmental chondrogenesis and their relative GO function, which may offer opportunities for the research for cartilage tissue engineering and novel insights into the prevention of OA in the near future.