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Introduction: Coronary artery disease (CAD) is the main cause of death and is characterized by atherosclerosis in coronary arteries. Inflammation plays a crucial role in the progression and development of atherosclerosis. Methods: The present study consisted of 132 Iranian individuals who underwent coronary angiography, 65 patients with CAD, and 67 controls. The matrix metalloproteinase-9 (MMP-9), TNF-α, IL-6, and vitamin D serum levels were measured by the ELISA technique. The gene expression of MMP-9 and tissue inhibitors of metalloproteinase (TIMP-1) was estimated by realtime PCR assay. Results: A considerable increase in levels and PBMC gene expression of MMP-9 and serum levels of IL-6 and TNF-α were found in CAD patients compared with controls. A significant decrease was detected in vitamin D levels of CAD patients in comparison with controls. A considerable direct correlation was found between MMP-9 levels and MMP-9 and TIMP1 gene expression in CAD patients. MMP-9 levels positively correlated with LDL-C in CAD patients. The correlation between TIMP1 gene expression and IL-6 levels was also negatively significant. There were positive correlations between MMP-9 levels with IL-6 and TNF-α serum levels in CAD patients. Conclusion: This study showed that the interaction between MMPs, TIMP1, and cytokines could play a role in the pathogenesis of atherosclerosis. The present study suggested that high levels of TNF-α and IL-6 and vitamin D deficiency in our studied patients could disturb the MMP-9/TIMP-1 balance and lipid metabolism, leading to plaque formation/ rupture in predisposed CAD patients. [ABSTRACT FROM AUTHOR]

Background: Excessive extracellular matrix (ECM) deposition in adipose tissue is a hallmark of fibrosis, leading to disrupted adipose tissue homeostasis and metabolic dysfunction. Hesperetin, a flavonoid compound, has shown promising anti-inflammatory, anti-obesity and anti-diabetic properties. Therefore, we investigated the anti-fibrotic effects of hesperetin, through targeting ECM components and matrix metalloproteinase enzymes. Methods: 3T3-L1 cells were cultured in DMEM, containing 10% FBS and 1% penicillin/streptomycin. Cells were treated with a range of hesperetin concentrations, and the cell viability was determined using MTT assay. Subsequently, the expression of genes encoding collagen VI, osteopontin, matrix metalloproteinase-2 (Mmp-2) and Mmp-9 was analyzed using specific primers and real-time PCR technique. To evaluate protein levels of collagen VI and osteopontin, Western blotting was performed. Results: Hesperetin affected the viability of 3T3-L1 adipocytes with IC50 of 447.4 µM, 339.2 µM and 258.8 µM (24 h, 48 and 72 h, respectively). Hesperetin significantly reduced the gene and protein expression of both collagen VI and osteopontin in 3T3-L1 pre-adipocytes, in a time- and dose-dependent manner. Hesperetin was also able to cause a remarkable decline in gene expression of Mmp2 and Mmp9. Conclusion: Hesperetin could potently reduce the production of markers of adipose tissue fibrosis and might be considered a potential anti-fibrotic compound in obesity. Thus, hesperetin has the potency to be used for the treatment of obesity-associated fibrosis. [ABSTRACT FROM AUTHOR]

Background: Based on the critical role of MT4-MMP and MT6-MMP in carcinogenesis, we focused on MT4-MMP and MT6-MMP circulating levels in patients with thyroid nodules. Methods: Plasma samples were collected from three groups, including papillary thyroid cancer (PTC; n = 30), multinodular goiter (MNG; n = 30), and healthy subjects (n = 22). Enzyme-linked immunosorbent assay (ELISA) was used to obtain the concentration of MT4-MMP and MT6-MMP in the three groups. Results: Analysis of data demonstrated increased levels of MT4-MMP (PTC: 4.90 ± 1.35, MNG: 4.89 ± 1.37, and healthy: 3.13 ± 1.42) and MT6-MMP (PTC: 8.29 ± 2.50, MNG: 7.34 ± 2.09, and healthy:5.01 ± 2.13) in thyroid nodules by comparison with healthy subjects (P < 0.05). There were no significant differences in the levels of the two MT-MMPs between PTC and MNG (P > 0.05). Increased plasma levels of MT4-MMP (odds ratio = 2.48; 95% CI: 1.46--4.19; P = 0.001) or MT6-MMP (odds ratio = 1.81; 95% CI: 1.29--2.53; P = 0.001) were associated with increased risk of PTC tumorigenesis. Interestingly, a strong positive association was observed between MT4-MMP and MT6-MMP in the three groups (PTC: r = 0.766**, P = 0.000; MNG: r = 0.856**, P = 0.000; healthy r = 0.947**, P = 0.000). Areas under the ROC curve for MT4-MMP and MT6-MMP were 0.82 and 0.96, respectively. At the cutoff value > 4.7 (ng/mL), MT4-MMP and MT6-MMP showed a sensitivity of 63.3% and 90.0%, respectively, with 100% specificity. Conclusion: Our work has led us to imply that the higher levels of MT4-MMP and MT6-MMP are closely linked with both PTC and MNG tumorigenesis. They may probably promote the development of thyroid lesions; however, more research is needed to further clarify the current findings. [ABSTRACT FROM AUTHOR]

Introduction: Irisin is a newly discovered myokine released from skeletal muscle during exercise. The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play a key role in the metastatic process via degrading extracellular matrix. The aim of this study was to investigate the effect of irisin on expression of metastatic markers MMP2 and MMP9 and induced apoptosis in human prostate cancer cells. Methods: In this study, we examined the effect of different concentrations of irisin on induced apoptosis and cell viability of two cell lines, LNCaP and DU-145, by using flow cytometry and MTT assay, respectively. The expression of MMP2 and MMP9 genes was also analyzed by real-time PCR after irisin treatment. Data were analyzed using the comparative cycle threshold 2−∆∆Ct method. Results: Cell viability was reduced in both LNCaP and DU-145 cell lines at different concentrations of irisin. However, this decreased cell viability was strongly significant (p < 0.05) only at 5 and 10 nM concentrations of irisin in the LNCaP cell line. Furthermore, irisin could induce apoptosis in both cell lines at a concentration of 10 nM compared to 5 nM. Real-time PCR results also demonstrated a decreased expression in MMP2 and MMP9 genes in a concentration-dependent manner in both cell lines. Conclusion: These results showed the anticancer effects of irisin on cell viability of both LNCaP and DU-145 cell lines and also on the expression of MMP2 and MMP9 genes occurred in a dose- and time-dependent manner. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Present study has been carried out to analyze the IL-17R gene expression in PBMCs of patients with premature coronary artery disease (CAD) in comparison to normal controls. BACKGROUND: Premature CAD results in disability and lack of quality of life over the years and consequent mortality. Cardiovascular disease (CVD) has global distribution. In 2022, CAD is the leading cause of mortality in the United States and Iran. IL-17 cytokine family plays an important role in promoting inflammation and producing pro-inflammatory cytokines, chemokines, and matrix metalloproteinases. METHODS: Entirely, 60 subjects were entered into this examination. The case group consisted of 30 subjects with CAD as well as the control group which consisted of 30 healthy persons. The real-time quantitative reverse transcription PCR assay was used to find out, the relative expression (fold) level of IL-17R gene. RESULTS: Our findings indicated that, the relative expression (fold) level of IL-17R gene in the patients group showed an increased level as compared to the control group. The analysis of findings obtained in this study showed that the patient group is significantly different from the control group regarding the IL-17R mRNA level (fold) (p = 0.035). CONCLUSION: It has been concluded that IL-17R plays an important role in the pathogenesis of CAD. It follows that superior understanding of IL-17/IL-17R signaling way will be vital for innovating novel therapeutic targets that will facilitate the designing of new drugs for the management of patients (Ref. 40). Text in PDF www.elis.sk KEY WORDS: gene expression, premature CAD, IL-17R. [ABSTRACT FROM AUTHOR]

One of the most common and deadly brain tumors is Glioblastoma multiforme (GBM). Due to recent advances in angiogenesis and its related key factors, this process as a hallmark in glioblastoma has attracted more consideration from the research community. Temozolomide (TMZ) as the first-line treatment used to treat GBM but, resistance to TMZ limits its effectiveness and the need for better treatments is still felt. Therefore, we aimed to examine the Synergistic effects of Gefitinib (GFI) in combination with Temozolomide on VEGF and MMPs in glioma cell line (U87MG). Our results displayed that GFI could induce cytotoxic effects in U87MG with IC50 values of 11 μM. U87MG cells produced large amounts of VEGF without any stimuli, and the results showed that GFI in combination with TMZ caused a significant decrease in VEGF production in these cells. In this study, we demonstrated that after treating with TMZ and GFI, there was more decrease in the levels of MMP 2 and 9 secretions in cells than treatment with GFI and TMZ doses alone. This study indicates synergistic effects of GFI plus TMZ against glioma are mediated by the potentiated anti-angiogenesis. Therefore, it can be considered as a promising plan for future studies. [ABSTRACT FROM AUTHOR]

Background: Cardiac remodeling following myocardial infarction is a pathological process. We aimed to examine the effect of early short-term minocycline on the left ventricular function following ST-elevation myocardial infarction treated by the primary percutaneous coronary intervention.Methods: In this double-blind, randomized controlled trial, data of 73 patients STEMI patients who were candidates for primary PCI were enrolled. Patients were then randomized to receive minocycline 50 mg orally, followed by 50 mg once a day for 5 days or a placebo with the same schedule. Measurement of serum matrix metalloproteinase-9 (MMP-9) and 2-dimensional speckle tracking echocardiography was performed at baseline and between 4 and 6 months after discharge. Then the demographic, clinical, echocardiographic, and angiographic data, as well as the levels of MMP-9, were compared between the study groups.Results: There was no statistically significant difference between the study groups regarding the baseline characteristics. Serum levels of MMP-9 did not change following the intervention within each group and were not significantly different between the groups after follow-up. In the follow-up echocardiography, we also did not observe any difference between the two groups CONCLUSION: In this study, we did not observe any effect of minocycline on cardiac remodeling based on 2-dimensional speckle tracking echocardiography and MMP-9 levels.Trial Registration: Iranian Registry of Clinical Trials IRCT201411188698N15 . Registered on 22 June 2015, prospectively. [ABSTRACT FROM AUTHOR]

The serum levels and activity of matrix metalloproteinases (MMPs) are associated with the risk of coronary artery calcification (CAC). We sought to investigate the association between MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs with MMP-2 and MMP-9 serum levels and activity in individuals with CAC. One hundred and fifty-five cases with CAC and 155 healthy individuals as control group from West of Iran were included and frequency of genotypes and alleles of rs243866 and rs3918242 in MMP-2 and MMP-9 genes were determined using PCR–RFLP. We also investigated the serum levels of MMP-2 and MMP-9 and their activity using ELISA and gelatin zymography, respectively. Additionally, serum biochemical parameters including FBS (fasting blood sugar), urea, creatinine, cholesterol, triglyceride, HDL (high-density lipoprotein), LDL (low-density lipoprotein), calcium, and phosphorus as well as blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) were measured. Our results showed that both serum levels of MMP-2 and MMP-9 (P < 0.001) and their activity (P < 0.001) were higher in individuals with CAC when compared to the control group. Carrying A and T alleles in MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs, respectively, may predispose the individuals to CAC by acting as the risk factors. Serum levels and activity of MMP-2 and MMP-9 were found to be higher in CAC cases when compared to the healthy controls. Carriers of A allele in rs243866 SNP and T allele in rs3918242 SNP were shown to have higher MMP-2 and MMP-9 serum levels and activity that may result in increased ECM degradation and support the initiation and development of calcification. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The aim of this study was to evaluate the effects of hydro-alcoholic extract of spinach (HES) on hepatic and serum measurements of NAFLD in a rat model. Methods: In the prevention phase, 18 Sprague–Dawley rats were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, or a chow diet for seven weeks. For the treatment phase, after the induction of NAFLD, they were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, a chow diet, or a chow diet plus 400 mg/kg HES for four weeks (n = 6). Results: Administration of HES combined with high-fat diet in rats was associated with decreased food intake (P < 0.01), weight loss (P = 0.01), and increased superoxide dismutase (SOD) (P = 0.02) enzyme activity in the liver, at the end of the prevention phase. hs-CRP (P < 0.05), PTX-3 (P < 0.05), and TNF-α (P < 0.05) gene expression in the liver were decreased and PPAR-γ (P < 0.05) gene expression in the liver was increased by spinach intake, both in the prevention and treatment phases. Furthermore, administration of spinach in the treatment phase increased serum TAC (P = 0.03) and hepatic GPX (P = 0.01) enzyme activity. Conclusion: Taking into account the potential beneficial effects of HES on prevention and treatment of NAFLD in the present study, to confirm these findings, we propose that further clinical trials be conducted on human subjects with NAFLD. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a degenerative joint disease that causes a variety of adverse health effects. Considering the need to identify additional effective therapeutic options for OA therapy, we investigated the effect of co-injection of apigenin and synovial membrane-derived mesenchymal stem cells (SMMSCs) on OA in male rats' knee joints. Methods: The study was performed in 2019 at the Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran. Anterior cruciate ligament transection (ACLT) was used to induce OA. For three weeks, male Sprague-Dawley rats (eight groups, n=6 each) were treated once-weekly with intra-articular injections of apigenin alone or in combination with SMMSC (three million cells), phosphate-buffered saline, or hyaluronic acid. After three months, the interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF- α), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the cartilage homogenate. The expression of extracellular matrix (ECM) components including collagen 2a1, aggrecan, IL-1β, TNF-α, inducible nitric oxide synthase (iNOS), transcription factor SOX-9, and matrix metalloproteinases 3 and 13 were assessed using real-time polymerase chain reaction (RT-PCR) analysis. Radiological evaluation and histopathological assessment were used to evaluate the knees. Results: Levels of TNF-α (P=0.009), MDA (P0.001>), and IL-1β (P<0.001) decreased and the level of SOD increased (P=0.004) in the apigenin 0.3 µM with SMMSCs group. RT-PCR analysis indicated that IL-1β in the apigenin 0.3 µM with SMMSCs group reduced significantly (P>0.001). This group also exhibited increased expression levels of SOX-9, collagen 2a1, and aggrecan (P>0.001). Conclusion: Apigenin may have supplementary beneficial effects on cell therapy in a rat model of OA due to its possible effect on the reduction of oxidative stress, suppression of inflammation, and promotion of production of ECM components. [ABSTRACT FROM AUTHOR]

Objectives: matrix metalloproteinases including matrix metalloproteinase-2 play a key role in endometrial extra cellular matrix breakdown in endometriosis. Aberrant expression of matrix metalloproteinase-2 has been reported in eutopic and ectopic endometrial tissue of endometriosis patients so altered expression of matrix metalloproteinase-2 due to polymorphisms may lead to establishment and progression of endometriosis. In this study the association between -735 C/T (rs2285053) and -1575 G/A (rs243866) variants of matrix metalloproteinase-2 gene with presence of endometriosis in an Iranian population were investigated for the first time.Study Design: A case-control association study was conducted to investigate the role of MMP-2-735 C/T and _1575 G/A variants in development of endometriosis. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine genotype frequencies of these variants in 100 endometriosis patients and 200 normal samples. Total genomic DNA was extracted from blood samples and single-nucleotide polymorphism flanking regions were amplified using designed specific primers. Enzymatic digestion was performed using Pag I and Hinf I restriction enzymes for rs2285053 and rs243866 variants, respectively. Statistical analysis was ascertained using statistical package for social science version 16 and "SHEsis" software.Results: There were no significant differences in genotype frequencies of rs2285035 (-735C/T) variant between case and control groups (CC + CT vs. TT p = 0.40; OR = 0.50, 95 % CI 0.100-2.551). There were also no significant differences for C allele frequencies in both case and control groups (p = 0.9). For variant rs243866 (-1575 G/A) the differences in genotype frequencies between case and controls group were determined to be significant (GG + GA vs. AA p = 0.041; OR = 6.46, 95 % CI 0.82-50.43). The frequency of G allele was significantly different in case and control groups (p = 0.037).Conclusion: In conclusion, existence of rs243866 variant in promoter region of matrix metalloproteinase-2 gene can increase the risk of endometriosis in Iranian women. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases (MMPs) play important role in Multiple Sclerosis (MS), an autoimmune and neuro-inflammatory disease. It has been demonstrated that two important polymorphisms, the –1562 C/T and microsatellite (CA)n near the –90 position in the promoter region of MMP-9 gene are associated with increased MMP-9 expression, through influencing transcriptional process in MS, also some autoimmune diseases as well as cancers. In this study, the possible association of these gene polymorphisms with MS susceptibility, severity as well as age of onset in samples from south-west of Iran were examined. Methods: Polymorphisms for two regions, –1562 C/T (rs3918242) and –90 (CA)n repeat was analyzed in 170 south-west Iranian patients with MS and 200 healthy controls. Results: Results suggested that a genetic polymorphism of the MMP-9 promoter region may influence the susceptibility to MS. Significant increase frequencies of the –1562 T and long (CA)n alleles were found in patients with MS compared to controls. Carriers of two polymorphisms were younger age at disease onset. The disability status of patients, moreover, has been consistently increased by the association of T variants. Conclusion: This study suggests that genotypes and alleles of MMP-9 –1562 C/T gene as well as (CA)n polymorphisms are associated with higher MS susceptibility due to increased MMP-9 protein levels. This finding, therefore, supports the hypothesis of a significant role of this gene in the disease. [ABSTRACT FROM AUTHOR]

Objectives: The current study aimed to investigate the association of matrix metalloproteinase- (MMP-) 1, -2, -3, -7, and -13 gene polymorphisms with chronic periodontitis (CP) in an Iranian population., Materials and Methods: In this case-control study, 87 subjects with CP and 89 periodontally healthy subjects were allocated to case and control groups, respectively. Subjects' venous blood samples (5 cc) were collected, and DNA extraction was performed. A spectrophotometer was utilized to assess the concentration of extracted DNAs. The desired gene polymorphisms were examined using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) followed by electrophoresis. Statistical analyses were done using the Pearson Chi-Square test, odds ratio, and t-Test using SPSS Version 28., Results: The MMP-1 (-1607 1G/2G) rs1799750, MMP-3 (-1171 5A/6A) rs3025058, and MMP-7 (-181 A/G) rs11568818 gene polymorphisms significantly differed between case and control groups (PV = 0.019, 0.007, and 0.028, respectively). In contrast, the gene polymorphisms of MMP-2 (-1306 C/T) rs243865 and MMP-13 (-77 A/G) rs2252070 did not make a significant difference. Regarding allele frequencies, the presence of the 2G allele in the MMP-1 (-1607) rs1799750 genotype increased the CP susceptibility significantly, while subjects with the 6A allele in their MMP-3 (-1171) rs3025058 genotype showed significantly lower susceptibility to CP (PV = 0.008 and < 0.001, respectively)., Conclusion: In the studied population, gene polymorphisms in the DNA sequences of MMP-1 (-1607 1G/2G) rs1799750, MMP-3 (-1171 5A/6A) rs3025058, and MMP-7 (-181 A/G) rs11568818 may have impacts on CP incidence., Clinical Relevance: Clinicians should be cautious about the association between MMP-1, MMP-3, and MMP-7 gene polymorphisms and the incidence of chronic periodontitis during periodontal treatment planning., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Colon cancer is the third most common cancer worldwide, responsible for more than half a million deaths every year. Metalloproteinases (MMP2 and MMP9) participate in tumor invasion and metastasis because of their ability to degrade the extracellular matrix (ECM). Materials and Methods: The expression levels of MMP2 and MMP9 as well as tissue inhibitor metalloproteinases TIMP1 and TIMP2 were determined by immunohistochemistry in 42 Iraqi patients diagnosed with colon cancer as well as in 18 benign tissues. Results: Immunohistochemistry revealed that the protein expression levels of MMP2 ,MMP9, TIMP1 and TIMP2 increased by 83%, 72%, 64%, and 57%, respectively, in patients with colon cancer tissues compared with 19%, 28%, 23%, and 16%, respectively, in benign tissues. Conclusion: MMP2, MMP9, TIMP1 and TIMP2 expression levels in Iraqi patients with colon cancer could be used as potential markers that can predict tumor behavior, progression, and prognosis. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth common cancer worldwide. A hallmark of cancer progression is degradation of the extracellular matrix by matrix metalloproteinases (MMPs) that allows cancer cells to invade the surrounding tissue. Objectives: The purpose of this studywasto evaluate the levels of MMP-2and9inserumandsalivary of HNSCCpatientsandcompare it with a healthy group. Methods: Twenty patients with newly diagnosed HNSCC, who had not received any treatment, referred to Omid and Ghaem hospitals, Mashhad, Iran, and twenty healthy controls were voluntarily included in this study. Salivary and blood samples were collected from both groups and the concentration of MMP-2 and MMP-9 were measured by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed by SPSS using Student t-test or Mann-Whitney with significance level of ≤0.05. Results: In cancer patients, the serum level of MMP-9was significantly higher than that of in the healthy group (P< 0.001). However, salivary MMP-9 was higher in cancer patients, this difference was not significant (P = 0.736). There was no significant difference between the study groups for the levels of serum (P = 0.283) and salivary MMP-2 (P = 0.764). There was a correlation between salivary and serum levels of both markers in cancer patients (P = 0.046 and P = 0.011 for MMP-2 and MMP-9, respectively), on the contrary, there was not a correlation between them in the healthy controls (P = 0.628 and P = 0.064, for MMP-2 and MMP-9, respectively). A direct correlation between the salivary level of MMP-9 and tumor grade was also detected (P = 0.045). Conclusions: The salivary analysis indicates that an altered composition forMMPsin HNSCC, suggesting a potential diagnostic tool for oral cancer. The serum level of MMP-9 appears to be a reliable marker for early diagnosis in HNSCC patients. [ABSTRACT FROM AUTHOR]

Purpose Cancer disease is the second cause of death in the world. Nowa days, high percentage of drugs, which are involved in treatment of cancers, have natural origin. Introduction of microalgae strains as anti-cancer drugs origin is a valuable approach for cancer therapy. Methods In the present study we describe the isolation, characterization, and anti-proliferative activity of a new microalga strain (Picochlorum sp. RCC486) from Iran. The cytotoxic activity of four different algal extracts including methanol, ethyl acetate, chloroform, and hexane were evaluated against MDA-MB-231, MCF-7, Hep-G2, and A-549 cell liens. Cell viability was determined using MTT assay in both monolayer and spheroids 3D cultures. The apoptosis was confirmed by different methods such as AO/EB and Annexin V-FITC/PI double staining, caspase-3 colorimetric assay, ROS and MMP assay. Results The results of MTT assay and fluorescent double staining confirmed that methanol and ethyl acetate extracts showed the best cytotoxic activity against the cancer cell lines. The production of ROS, caspase-3 activity and depolarized MMP were quite significant in MDA-MB-231 cell line treated with methanol and ethyl acetate extracts. Conclusion In this research we revealed that cytotoxicity and apoptotic effects of the methanol and ethyl acetate extracts in human cancer cells make them good candidates for further pharmacological studies to discover effective drugs for cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases-2 and -9 play important roles in the development of breast cancer by hydrolyzing the extracellular matrix. Since -1306C/T and -1562C/T polymorphisms are located at the promoter regions of the matrix metalloproteinase- 2 and -9 genes, respectively, C to T substitution may affect promoter activity and impact the rate of extracellular matrix degradation and cancerous cell proliferation. Therefore, we aimed to determine the genotype and allele frequencies of these polymorphisms in Iranian healthy women and women with breast cancer. We have also examined the correlation of genotypes with clinicopathological parameters such as tumor type, tumor size, and metastasis to lymph nodes. Methods: This case-control study enrolled 200 women with breast cancer and 200 age-matched healthy women. DNA was extracted, and we determined the genotype and allele frequencies of -1306C/T matrix metalloproteinase-2 and -1562C/T matrix metalloproteinase-9 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. Additionally, tumor size (<20 mm/>20 mm), tumor type (ductal/non-ductal), and metastasis (yes/no) were determined. Results: Genotype and allele frequencies of the -1306C/T matrix metalloproteinase- 2 polymorphism showed no significant association with the occurrence of breast cancer. Genotype and allele distribution differed in the -1562C/T matrix metalloproteinase- 9 polymorphism and indicated a 4.83-fold increase in the risk of breast cancer for T allele carriers. There was no likelihood of any interaction found between the two polymorphisms and susceptibility to breast cancer. In addition, the -1562C/T matrix metalloproteinase-9 T allele showed an association with metastasis to lymph nodes but we observed no association between the -1306C/T matrix metalloproteinase- 2 polymorphism and clinicopathological features. Conclusion: The -1562C/T matrix metalloproteinase-9 polymorphism is involved in the pathogenesis of breast cancer in Iranian women. The T allele may increase the risk of disease. [ABSTRACT FROM AUTHOR]

Background Coronary Artery Disease (CAD) represents the most important cause of sudden cardiac death. Interaction between genetic and environmental factors, individual susceptibility of the development of CAD is one of the MMP2 genes. Genetic variants’ dysfunction of the MMP2 gene associated with the risk of CAD. The aim of the present study is to assess possible association between risk of Coronary Artery Disease and MMP2-1306C/T polymorphism. Methods This case-control study contains a total number of 344 subjects, including 215 patients with CAD and 129 of controls. Genomic DNA was isolated from whole blood and genotyping was performed by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR- RFLP) method. Results This study reveals the result that about 3.5% of CAD patients had TT genotype while 30.4% of them had CT genotype. Corresponding figures for subjects without CAD were zero and 52.6% respectively. These differences were statistically significant (P = 0.002). Frequencies of T allele among patients with and without CAD were 18.71% and 26.28% respectively (p = 0.04). The odds ratio between T allele and CAD was 0.64 (p = 0.055). we couldn’t trace significant differences among alleles in Gensini score, Gesnsini score’s median among patients carried out TT, CT and CC genotypes were 4, 2 and 2 respectively (p = 0.3). Conclusions Result of this study provides some evidences that the MMP2-1306 polymorphism can be associated with coronary artery disease. Further longitudinal studies including more sample sizes are required to confirm this protective effect. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases (MMPs) are a family of proteinases and have the vigorous capacity to degrade all parts of the extracellular matrix. MMP enzymes strongly participate in physiological processes such as normal tissue remodeling and wound healing and in pathology of pulmonary diseases. They are released in response to environmental stimuli such as toxins and regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Sulfur mustard (SM) is a chemical toxic which can cause severe permanent damages to lung tissues. The aim of this study was assessing the possible role of MMP-9 and TIMPs in SM-induced lung symptoms and signs in exposed patients 20 years after exposure. Methods: Totally, 372 male volunteers with a history of SM exposure and 128 age- and sex-matched unexposed controls participated and were divided into three groups: normal, mild and moderate-severe. All participants underwent clinical evaluation and pulmonary function tests and serum concentrations of MMP-9 and its inhibitors were measured using the ELISA technique. Results: Serum level of MMP-9 was increased in the SM exposed group who had moderate-severe pulmonary complications compared with the SM exposed with normal lung (2.321 ±2.836 vs. 1.546 ±2.176, P = 0.001) while only the MMP-9/TIMP-4 complex was elevated in the SM exposed with normal lung individuals compared to its corresponding control group (85 ± 265 vs. 82 ± 222, P = 0.025). Although MMP-9 and its inhibitors did not show any correlation with spirometry findings, elevated circulating MMP-9 was detected in SM exposed patients with chronic chough and hemoptysis (P = 0.013 and P= 0.013 respectively). Conclusion: High level of tissue disruption and remodeling mediators could influence lung structure in long-term after SM exposure. The correlation of clinical evaluation with these factors efficiently helps us to identify important effectors. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinase 9 (MMP9) -1562C>T (rs3918242) polymorphism has been proposed as a risk factor for coronary artery disease (CAD) with conflicting results. The aim of the present study was to investigate the association of -1562C>T genetic polymorphism, gene expression and circulating levels of MMP9 with CAD risk in an Iranian subpopulation in in Zanjan City. Materials and Methods: This was a retrospective case-control study we investigated retrospectively 100 patients with angiographically verified CAD and 100 matched controls. Genotyping of -1562C>T polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gene expression levels and circulating levels of MMP9 was determined by real-time reverse transcription-PCR and enzyme immunoassay method, respectively. Statistical analysis was done using Student's i-test or Chi-square test by SPSS 16 software. Results: The mean circulating levels of MMP9 were significantly higher in CAD Group than control group (P = 0.002). Mean plasma levels of MMP9 were also significantly higher in triple vessel stenosis patients than double vessel or single vessel stenosis patients (P < 0.001). Moreover, mean plasma levels and gene expression levels of MMP9 were significantly higher in T allele carrier than C allele carrier of MMP9 -1562C>T polymorphism (P = 0.002, P = 0.01, respectively). However, genotype and allele frequencies of MMP9 -1562C>T polymorphism were similar between CAD patients and controls (P > 0.05). Additionally, the -1562C>T polymorphism of MMP9 gene didn't increase the risk of CAD in dominant (P = 0.537) or recessive (P = 0.249) genetic models. Conclusion: Our study demonstrated that circulating levels of MMP9 but not -1562C>T polymorphism of MMP9 gene may be a risk factor for development and severity of CAD in an Iranian subpopulation in Zanjan. [ABSTRACT FROM AUTHOR]

The article discusses a research which explores the occurrence of matrix metalloproteinases (MMP)-7 A-181G polymorphism for patients with breast cancer in western Iran.

Background and Objectives Gelatinases are a subgroup of matrix metalloproteinases (MMPs) and have an important role in tumor growth and angiogenesis. In this regard, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) have particular value. Isosorbide dinitrate (a nitric oxide donor) has been broadly used in treatment of cardiac diseases and its inhibitory effect on angiogenesis and tumor growth have been reported in vivo. In this study, the effect of isosorbide dinitrate on gelatinase-A and gelatinase B activity in leukemic cell lines has been assessed in vitro. Materials and Methods MOLT-4, JURKAT and U937 leukemic cells were cultured in complete RPMI medium and then incubated with different concentrations of isosorbide (4 × 10-7, 4 × 10-6, 4 × 10-5, 4 × 10-4 M) in the presence of phorbol myristate acetate (PMA) (25 ng/mL), as a gelatinase inducer, for 24 hours. Afterwards, the gelatinase A and B activity in the cell culture medium was evaluated by gelatin zymography. Results The gelatinase A and B activity of MOLT-4, JURKAT and U937 leukemic cells treated with isosorbide did not show any significant difference with control. The gelatinase A activity was 1 ± 0.0 and 1.04 ± 0.06 in the control and 4 × 10-4 M concentration of the isosorbide in MOLT- 4 cell line, respectively. Conclusions In this study, isosorbide did not show any significant effect on gelatinase A and B activity in leukemic cells. The anti-tumoral and anti- angiogenic effect of isosorbide was reported by others to be possibly due to non-gelatinase activity mediated mechanism. [ABSTRACT FROM AUTHOR]

As there is limited and inconsistent evidence in potential role of vitamin D on insulin resistance and matrix metalloproteinases, this study aimed to examine the effect of vitamin D supplementation on glucose homeostasis, insulin resistance, and matrix metalloproteinases in obese subjects with vitamin D deficiency. A total of 44 participants with serum 25-hydroxyvitamin D (25(OH)D) level ≤ 50 nmol/L and body mass index (BMI) 30-40 kg / m 2 were randomly allocated into receiving weight reduction diet with either 50 000 IU vitamin D 3 pearl ( n = 22) or placebo ( n = 22) once weekly for 12 weeks. Primary outcomes were changes in fasting serum glucose (FSG), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and matrix metalloproteinases (MMPs). Secondary outcomes were changes in weight, BMI, 25(OH)D, calcium, phosphorous and parathyroid hormone (PTH). Sun exposure and dietary intakes were also assessed. Serum levels of 25(OH)D3 increased significantly with a simultaneous decrease in serum concentration of PTH in the vitamin D group. Weight, BMI, FSG, and MMP-9 decreased significantly in both groups, and there were significant differences in changes in weight, serum 25(OH)D3, PTH, and MMP-9 levels between the groups. Within- and between-groups analysis revealed no significant differences in serum calcium, phosphorous, serum insulin, HOMA-IR, QUICKI, and MMP-2 after intervention. Our results indicated that improvement in vitamin D status resulted in greater reductions in weight and MMP-9 during weight loss. These preliminary results are sufficient to warrant a bigger study group.

Background: Osteoarthritis (OA) is one of the commonest forms of musculoskeletal disorders that leads to joint degeneration and has a major impact on patients' quality of life. Experimental and in vitro studies have suggested the protective roles of pomegranate juice (PJ) as a rich antioxidant source for mitigating cartilage inflammation. In this interventional study, 38 patients with knee OA were randomly divided into two groups: PJ or control for 6 weeks to evaluate the effect of this intervention on clinical signs, inflammation and antioxidant status., Results: Significant decreases in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) total score (P = 0.01), stiffness score (P = 0.00) and physical function score (P = 0.01) were observed in PJ group after the intervention. The means of serum levels of matrix metalloproteinase (MMP)-13 was significantly decreased (P = 0.02) and glutathione peroxidase was increased in the intervention group compared with the control group after the study period (P = 0.02)., Conclusions: According to the findings of this clinical trial, PJ consumption can improve physical function and stiffness, decrease breakdown cartilage enzymes and increase antioxidant status in patients with knee OA. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)