MMP-9 In Patients Research Articles

Serum metalloproteinase-7 as a biomarker of progressive pulmonary fibrosis

IntroductionProgressive pulmonary fibrosis (PPF) corresponds to any fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) that presents clinical, physiological and/or radiological evidence of disease progression similar to IPF. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis and are associated with disease progression and reduced survival in IPF and other fibrotic ILDs.AimThis study aimed to investigate the role of the serum levels of MMP-1 and MMP-7 in patients with fibrotic non-IPF ILD as possible biomarkers of patients at risk of developing PPF.MethodsNewly diagnosed patients with fibrotic non-IPF ILD were included in this study. Serum levels of MMP-1 and MMP-7 were quantified at baseline, and disease progression was monitored. PPF was defined according to the recent ATS/ERS/JRS/ALAT Clinical Practice Guidelines.ResultsSeventy-nine patients with fibrotic non-IPF ILDs were included and classified as having PPF or non-PPF. Significantly higher levels of MMP-7, but not MMP-1, were detected in the PPF group (p=0.01). MMP-7 was independently associated with PPF (aOR=1.263; 95% CI 1.029—1.551, p=0.026) after adjustment for sex, age and smoking history. A cut-off value of 3.53 ng·mL−1for serum MMP-7 levels had a sensitivity of 61% and a specificity of 74% for predicting PPF in non-IPF ILDs.ConclusionsIn patients with fibrotic non-IPF ILDs, serum MMP-7 levels were significantly greater in the subgroup of patients meeting the PPF criteria at follow-up. This can be considered and further investigated as a possible biomarker to identify fibrotic ILD patients at risk of PPF.

Association between matrix metalloproteinase-9-1562C/T gene polymorphism and MMP-9 serum level in rheumatoid arthritis

ABSTRACT Background Rheumatoid arthritis (RA) is an autoimmune disease indicated by joint inflammation and cartilage destruction. Matrix metalloproteinase (MMP) enzymes play an influential role in inflammation by affecting the invasion and degradation of anatomical barriers. In this way, the current study investigated the relationship between the MMP-9-1562C/T gene polymorphism and this enzyme’s serum level in RA. Methods The serum levels of MMP-9 in RA patients and healthy controls were measured using the enzyme-linked immunosorbent assay (ELISA). RA was confirmed using rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and C-reactive protein (CRP). Then the MMP-9-1562C/T gene polymorphism was analyzed utilizing polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Also, multivariate analysis investigated the connection between this polymorphism and the risk of RA. Results In this study, the increase of MMP-9 in patients due to the development of single nucleotide polymorphism in the promoter region of this gene (−1562 C→T) was confirmed by increasing the frequency of heterozygous genotype (CT). Logistic regression analysis also demonstrated that the chance of development of RA is higher in people with CT/CC genotype than in other alleles. Conclusions We demonstrated that MMP-9-1562C/T gene polymorphism can play a significant role in the occurrence of RA.

Secondary Prevention of Multifocal Atherosclerosis Combined with Chronic Obstructive Pulmonary Disease

The problem of secondary prevention of multifocal atherosclerosis (MAS) combined with chronic obstructive pulmonary disease (COPD), is a leading cause of death in the world. Therefore, the search for drugs capable of affecting the destructive mechanisms underlying both MAS and COPD is an extremely urgent problem today. Objective — to reduce the risks of destabilization of atherosclerotic plaques by reducing the levels of metallomatrix metalloproteases (MMP)-2 and MMP-9 in patients on MAS combined with COPD. Materials and methods. The study included 62 men (68.1 ± 4.2) years old with MAS. All patients with MAS had clinical and functional signs of injury in coronary, cerebral and femoral vascular territories, 30 of these patients (group MAS-2) additionally had clinical and functional signs of COPD (GOLD-2). The control group (CG) consisted of 18 practically healthy men, aged (65.4 ± 3.7) years. Examination of the patients included echocardiography, dopplerography of the vessels of the neck and arteries of the lower extremities, determination of walking distance and ankle-brachial index, Holter ECG monitoring, spirography and determination of MMP-2 and MMP-9 levels in blood. Patients of both groups were prescribed cilostazol (50 mg twice a day) and GABA aminalon (250 mg twice a day) on the background of basic treatment. The course of treatment lasted 16 weeks. Results and discussion. During the initial examination of patients, MAS-2 group showed significantly (p < 0.001) lower volumetric blood flow in the studied arteries, and significantly (p < 0.01) higher levels of MMP-2 and MMP-9, as compared to CG, as well as with patients of the MAS-1 group. After 16 weeks of treatment, with the addition of cilostazol and aminalon, the level of MMP in the blood significantly (p < 0.05) decreased in both groups, in particular, in the MAS-2 group, in patients with the combined pathology of MAS and COPD, a significant decrease was found MMP-2 by 23.6 % (p < 0.01), and MMP-9 by 12.1 % (p < 0.05). Volumetric blood flow indicators increased significantly (p < 0.05) in all studied vascular territories, which led to improvement in clinical manifestations of the disease — a decrease in the number of painful and painless episodes of myocardial ischemia, and an increase in walking distance. Conclusions. The use of a complex therapy of statins, cilostazol and GABA in patients with MAS combined with COPD allows to reduce significantly the levels of MMP-2 and MMP-9, which ensures the stability of atheromatous plaques and significantly improves blood supply in vascular territories with atherosclerotic lesions.

Retracted: Investigation on Risk Stratification and the Prognostic Value of hs-TnT Combined with MMP-2 in Patients with Acute Coronary Syndrome.

[This retracts the article DOI: 10.1155/2021/1040171.].

Markers of Collagen Degradation in Remodeling and Diastolic Dysfunction of Left Ventricle in Patients with Arterial Hypertension

Introduction. Myocardial remodeling is a consequence or predictor of several cardiovascular diseases. The key process in myocardial remodeling is the degradation of collagen fibers, mediated by the activity of matrix metalloproteinases and their tissue inhibitor.The aim of this study was to evaluate serum levels of matrix metalloproteinase type 9 and tissue inhibitor of matrix metalloproteinase type 1 in female patients with arterial hypertension, myocardial remodeling, and diastolic dysfunction.Materials and methods. A cross-sectional study that included 84 postmenopausal women. All patients underwent echocardiography. Left ventricular remodeling was assessed according to Ganau classification, and diastolic function was evaluated using transmittal flow parameters. Serum analysis included the determination of MMP-9 and TIMP-1 levels using an enzyme-linked immunosorbent assay.Results. The median concentration of MMP-9 in the sample was 2 295.00 (923.60–4 114.00) ng/ml, TIMP — 1–17 010.00 (16 780.00–17 170.00) ng/ml. When evaluating the echocardiographic parameters of the patients included in the study, changes were revealed that indicate structural and functional remodeling of the LV and DD. 29 patients (35 %) had normal geometry, 6 patients (7 %) had concentric myocardial remodeling, 21 patients (25 %) had concentric myocardial hypertrophy, 28 cases (33 %) had eccentric myocardial hypertrophy. Statistically significant changes in the activity of MMP-9 and TIMP-1 were revealed in patients with various structural and geometric variants of remodeling. DD was detected in all patients included in the study: I degree was detected in 25 patients (30 %), II degree was determined in 59 cases (70 %). Using one-way analysis of variance, statistically significant differences in the level of MMP-9 in patients with grades I and II DD were determined. MMP-9 and MMP-9/TIMP-1 in patients with grade II DD are significantly higher than in patients with grade I.Discussion. Under pathophysiological conditions, the proteolytic properties of MMP-9 contribute to the stimulation of the immune response, initiating pathogenesis and aggravating the progression of the disease. Evaluation of the activity of MMP-9 and TIMP-1 in patients with arterial hypertension may be a marker of myocardial remodeling.Conclusion. An increase in the activity of matrix metalloproteinase type 9 and a decrease in the activity of a tissue inhibitor of matrix metalloproteinases type 1 were revealed in patients with arterial hypertension, myocardial remodeling and LV diastolic dysfunction. The level of MMP-9 is associated with the degree of diastolic dysfunction and the structural-geometric type of LV remodeling.

Omentin-1 May Be One Treatment Factor for Intravenous Thrombolysis of Acute Cerebral Infarction Through the Inhibition of NLRP3 Ubiquitination by AMPK Function: Preliminary Findings.

Acute cerebral infarction (ACI) is a common neurological disease that is associated with high morbidity, disability and mortality rates. At present, antiplatelet therapy is a necessary treatment for ACI. The present study aimed to investigate the effects of omentin-1 on the intravenous thrombolysis of ACI. The present study aimed to investigate the effects of omentin-1 on the intravenous thrombolysis of ACI. The mouse model of ACI was induced using male C57BL/6 mice through middle cerebral artery occlusion (MCAO). Meanwhile, the murine BV2 microglial cells were pretreated with 0.1 mg/ml of lipopolysaccharide (LPS), and then induced with 2 mM of adenosine triphosphate (ATP). The omentin-1 mRNA expression in patients receiving intravenous thrombolysis for ACI was down-regulated compared with the normal group. Additionally, the serum level of omentin-1 was negatively correlated with National Institute of Health Stroke Scale (NIHSS) score or serum level of IL-1β or MMP-2 in patients receiving intravenous thrombolysis for ACI. Meanwhile, the serum mRNA expression of omentin-1 was positively correlated with Barthel index or high-sensitivity C-reactive protein (hs-CRP) in patients undergoing intravenous thrombolysis for ACI. As observed from the in vitro model, Omentin-1 reduced inflammation, promoted cell growth, alleviated ROS-induced oxidative stress, and enhanced AMPK activity through activating NLRP3 ubiquitination. Omentin-1 presented ACI in the mouse model of ACI. Regulating AMPK activity contributed to controlling the effects of Omentin-1 on the in vitro model. Omentin-1 reduced neuroinflammation and ROS-induced oxidative stress in the mouse model of ACI, which was achieved by inhibiting NLRP3 ubiquitination through regulating AMPK activity. Therefore, omentin-1 may serve as a treatment factor for the intravenous thrombolysis of ACI in further clinical application.

Exploring the Molecular Mechanisms and Shared Gene Signatures Between Systemic Lupus Erythematosus and Bladder Urothelial Carcinoma.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased susceptibility to cancer, including bladder urothelial carcinoma (BLCA). This study investigates the shared molecular mechanisms and gene signatures between SLE and BLCA, shedding light on potential biomarkers and therapeutic targets. We compiled gene datasets related to SLE and BLCA from various databases and identified common genes. Differential gene expression analysis, protein-protein interaction networks, and hub gene identification were performed. We studied functional enrichment, immune infiltration, and transcription factor/miRNA regulation networks. We also explored gene-disease interactions and protein-chemical/drug networks. Hub gene expression levels and diagnostic values were validated in TCGA and GEO databases. Prognostic analysis was performed on the core gene MMP9 in the TCGA-BLCA database to study its prognostic value. Finally, the mRNA expression of MMP9 was verified in bladder cancer cell lines and BLCA patient blood. The diagnostic value of MMP9 for BLCA was verified by receiver operating characteristic(ROC) curve analysis of the expression of MMP9 in patients' blood. We identified 524 common genes between SLE and BLCA, enriched in pathways related to apoptosis and cytokine regulation. Immune infiltration analysis for two diseases. Transcription factors and microRNAs were implicated in regulating these common genes. The gene-disease network linked hub genes with various diseases, emphasizing their roles in autoimmune disease and cancer. Protein-chemical/drug networks highlighted potential treatment options. Finally, our study found that MMP9 is a potential therapeutic target with diagnostic and prognostic value and Immune-related biomarkers in patients with BLCA and SLE. Our study reveals shared molecular mechanisms, genetic signatures, and immune infiltrates between SLE and BLCA. MMP9 emerges as a potential diagnostic and prognostic biomarker in BLCA, warranting further investigation. These findings provide insights into the pathogenesis of SLE-associated BLCA and may guide future research and therapeutic strategies.

Screening and experimental validation of diagnostic gene in ulcerative colitis with anti-TNF-α therapy.

In clinical practice, the diagnosis of ulcerative colitis (UC) mainly relies on a comprehensive analysis of a series of signs and symptoms of patients. The current biomarkers for diagnosis of UC and prognostic prediction of anti-TNF-α therapy are inaccurate. The present study aimed to perform an integrative analysis of gene expression profiles in patients with UC. A total of seven datasets from the GEO database that met our strict inclusion criteria were included. After identifying differentially expressed genes (DEGs) between UC patients and healthy individuals, the diagnostic and prognostic utility of the DEGs were then analyzed via least absolute shrinkage and selection operator and support-vector machine recursive feature elimination. Subgroup analyses of the treated and untreated groups, as well as the treatment-response group and non-response group, were also performed. Furthermore, the relationship between the expressions of UC-related genes and infiltration of immune cells in the course of treatment was also investigated. Immunohistochemical (IHC) assay was used to verify the gene expression in inflamed UC tissues. When considering all the applied methods, DUOX2, PI3, S100P, MMP7, and S100A8 had priority to be defined as the characteristic genes among DEGs. The area under curve (AUC) of the five genes, which were all consistently over-expressed, based on an external validation dataset, were all above 0.94 for UC diagnosis. Four of the five genes (DUOX2, PI3, MMP7, and S100A8) were down-regulated between treatment-responsive and nonresponsive patients. A significant difference was also observed concerning the infiltration of immune cells, including macrophage and neutrophil, between the two groups (treatment responsive and nonresponsive). The changes in the expression of DUOX2 and MMP7 based on the IHC assay were highly consistent with the results obtained in the current study. This confirmed the mild to moderate diagnostic and predictive value of DUOX2 and MMP7 in patients with UC. The conducted analyses showed that the expression profile of the five identified biomarkers accurately detects UC, whereas four of the five genes evidently predicted the response to anti-TNF-α therapy.

The content of matrix metalloproteinase-1, -9 and tissue inhibitor of matrix metalloproteinase-1 in patients with bronchial asthma and obesity

Airway remodeling is a significant factor in the progression of respiratory failure in bronchial asthma (BA). Obesity can contribute to inflammation, and consequently – airway remodeling, by increased production of matrix proteinase (MMP). However, the mechanisms of remodeling in different phenotypes of BA, especially in comorbid patients, remain poorly understood. The aim of the research was to examine the levels of remodeling markers MMP-1, MMP-9 and tissue inhibitor of matrix proteinases (TIMP-1) in obese asthmatic patients, taking into account their age at the onset of BA, the severity of symptoms and the level of control. Material and methods. 195 patients with BA associated with obesity were examined. The control group consisted of 95 practically healthy people. Patients were divided into two groups: Group I included 100 patients with early onset, and Group II included 95 patients with late onset of BA. The study was approved by the Bioethics Commission of the Medical Institute of Sumy State University. Statistical analysis of the obtained results was carried out using the SPSS-17 program. Results. The content of MMP-1, -9 and TIMP-1 was higher in patients with early (129.40 ± 7.86; 177.30 ± 9.19; 142.40 ± 12.22 ng/ml, respectively) and late (196.60 ± 9.62; 289.80 ± 16.23; 187.50 ± 11.34 ng/ml, respectively) BA with obesity compared to practically healthy individuals (р < 0.005). Patients with late-onset BA associated with obesity likely had higher indicators than those with early BA. In patients with early BA, the levels of MMP-1, -9, and TIMP-1 were not significantly different depending on the severity of the disease (р > 0.05). However, in patients with severe late BA, the levels of these markers were higher compared to those with mild BA (р < 0.05). Levels of MMP-1 and MMP-9 in patients with early-onset and late-onset BA with obesity were higher in the absence of disease control compared to those in complete and partial control, but in late-onset exceeded those in early-onset. Conclusions. Considering the obtained results, it can be assumed that the level of MMP-1, MMP-9 and TIMP-1 in obese patients with BA can serve as biomarkers of airway remodeling, namely, the severity and the level of BA control.

Matrix metalloproteinase MMP-7 as a new prognostic biomarker for gastric cancer

BACKGROUND: According to statistics, gastric cancer is in a leading position among all gastrointestinal cancers. The most effective treatment for gastric cancer is surgery. There are now heterogeneous clinical outcomes for patients in the same stage of the disease. The main reason for this is the fact that differences in types of gastric cancer occur not only at the histological level, but also at the molecular level. Finding the universal biomarkers that can provide information about patient prognosis is a subject of interest to scientists around the world. MMP-7 is the smallest molecule in the family of matrix metalloproteinases that contributes significantly to oncogenesis by affecting apoptosis and degradation of the extracellular matrix. MMP-7 hyperexpression is associated with aggressive tumor phenotype and worsens prognosis in patients with gastric cancer. Therefore, MMP-7 can be a promising biomarker in the treatment of gastric cancer.
 AIM: To identify possible correlations between the expression of MMP-7 in patients with gastric cancer and their prognosis.
 MATERIALS AND METHODS: The study included samples of 80 patients diagnosed with diffuse gastric cancer, who were selected based on our inclusion and exclusion criteria. 30 sectional stomach samples were taken as a comparison group. Of the 80 patients included in the study, gastrectomy was performed in 55% cases (44 people) and gastric resection was performed in 45% cases (36 people).
 RESULTS: In our work, the expression level of MMP-7 0.8±0.07 was indicated as high, and the expression rate of 0.40±0.067 as low. During the study, we assessed the link between the level of MMP-7 expression and the clinical characteristics of the tumor. We evaluated the following indicators: the disease stage, the presence of lesions of lymph nodes, the size of the tumor. Patients with increased MMP-7 expression in tumor tissue have a better prognosis than patients with low MMP-7 expression.
 CONCLUSION: The results of our study showed high MMP-7 expression in tumor tissue, which allowed us to establish a correlation between MMP-7 expression and adverse clinical outcomes. The data obtained may indicate the possible use of MMP-7 as a biomarker for gastric cancer.

Association of plasma MMP-2 levels and prognosis of patients with intracerebral hemorrhage: a prospective cohort study

ObjectiveThe role of MMP-2 in patients with ICH is controversial and the impact of plasma MMP-2 level on clinical outcome is still unclear.Materials and methodsIn this study, the peripheral venous blood was acquired from 93 patients with ICH and 88 healthy controls within 24 h of hospitalization and at enrollment. We retrospectively investigated plasma MMP-2 levels of patients and healthy controls. The edema volume, the NIHSS score, the GCS score, and mRS were used to assess and quantify neurological deficit following ICH. Logistic regression analysis was configured to determine the independent relation of plasma MMP-2 levels with clinical outcomes. In addition, the plasma MMP-14 levels and complement C4 level were tested to explore the relationship with plasma MMP-2 level.ResultsThere was a significant reduction of plasma MMP-2 levels in ICH patients than that in healthy controls (38.02 ± 1.71 vs. 54.03 ± 2.15, p < 0.0001), and MMP-2 is negatively correlated with the edema volume (r = −0.2187, p < 0.05), NIHSS score (r = −0.2194, p < 0.05), blood leucocyte count (r = −0.2549, p = 0.012), and complement C4 level (r = −0.2723, p = 0.005). There is positive correlation between MMP-2 level and GCS score (r = 0.2451, p = 0.01) and MMP-14 level (r = 0.7013, p = 0.005). The multivariate analysis revealed that reduced plasma MMP-2 level is associated with elevated edema volume (OR = 0.2604, 95% CI [0.07 to 0.84], p = 0.02).ConclusionThe plasma MMP-2 level in patients with ICH is significantly lower than that of healthy controls, and plasma MMP-2 level may be a prognostic factor. Plasma MMP-2 levels are correlated with the clinical outcomes of patients and negatively correlated with blood leucocyte count and complement C4 level in patients with ICH.

COL4A3 Mutation Induced Podocyte Apoptosis by Dysregulation of NADPH Oxidase 4 and MMP-2

Podocyte apoptosis is a common mechanism driving progression in Alport syndrome (AS). This study aimed to investigate the mechanism of podocyte apoptosis caused by COL4A3 mutations. We recruited patients with autosomal dominant AS (ADAS). Patients with minimal change disease (MCD) were recruited as controls. Microarray analysis was carried out on isolated glomeruli from the patients and validated. Then, corresponding mutant human podocytes (p.C1616Y) and 129 mice (p.C1615Y, the murine homolog to the human p.C1616Y) were constructed. The highest differentially expressed genes (DEGs) from microarray analysis were validated in transgenic mice and podocytes before and after administration of MMP-2 inhibitor (SB-3CT) and NOX4 inhibitor (GKT137831). We further validated NOX4/MMP-2/apoptosis pathway by real-time polymerase chain reaction (PCR), immunohistochemistry, and western blot in renal tissues from the ADAS patients. Using microarray analysis, we observed that DEGs, including NOX4/H2O2, MMP-2, and podocyte apoptosis-related genes were significantly upregulated. These genes were validated by real-time PCR, histologic analysis, and western blot in corresponding mutant human podocyte (p.C1616Y) and/or mice models (p.C1615Y). Moreover, we found podocyte apoptosis was abrogated and MMP-2 expression was down-regulated both invivo and invitro by NOX4 inhibition, urinary albumin-to-creatinine ratio, 24-hour proteinuria; and renal pathologic lesion was attenuated by NOX4 inhibition invivo. Furthermore, podocyte apoptosis was attenuated whereas NOX4 expression remained the same by inhibition of MMP-2 both invivo and invitro. These results indicated that NOX4 might induce podocyte apoptosis through the regulation of MMP-2 in patients with COL4A3 mutations. Our findings provided new insights into the mechanism of ADAS.

Metalloproteinase 9 and its role in the pathogenesis of allergic diseases in children

Metalloproteinases (MMP) play a significant role in the mechanisms of maintaining chronic inflammation and tissue remodeling. The study of concentration changes in these enzymes in the blood serum of children with allergopathology is of great practical and scientific interest.Objective: to study the role of MMP-9 in the pathogenesis of allergic diseases in children. 180 children aged from 1 to 18 years passed a comprehensive clinical and laboratory examination. This study included patients suffering from bronchial asthma (BA) (n = 54), atopic dermatitis (AD) (n = 54) and combination of these pathologies (n = 72). Serum levels of MMP9 were determined by enzyme immunoassay using Cloud-CloneCorp® test systems (USA).The analysis of the obtained data showed that among patients with the established diagnosis of BA, the maximum concentration of this cytokine was registered in children with a moderate course of the disease. The conducted correlation analysis showed the presence of a significant correlation between the severity of asthma and the level of control over the disease (r = 0.63). Similar data was obtained in patients with a combination of BA and AD. In children of this group, there was also a significant increase in serum MMP-9 compared with healthy patients (p = 0.015). The concentration of this matrix metalloproteinase in serum was slightly higher among children with polyvalent sensitization than in patients with monoallergic etiology of the disease (p = 0.272). The values of MMP-9 in patients with only skin manifestations of atopy were significantly higher than in the control group (p = 0.025).The data we obtained showed that all the patients we examined had a significant increase in the level of MMP-9 in the blood serum, which indicates an important role of this cytokine in the pathogenesis of allergic diseases in children.

Serum Concentration of MMP-9 as a Predictive Biomarker for the Progression of Oral Cancer.

Oral cancer is the most prominent cancer subtype among all head and neck cancers, the incidence and prevalence of which has been consistently increasing in past years around the globe. At advanced stages, oral cancer imparts significant mortality, morbidity, and mutilation among the patients, and therefore, diagnosis and treatment of the disease at early stages are considered the optimum strategy for the management of the disease. Since molecular changes appear earlier than physical symptoms, several molecular biomarkers are currently being investigated for their role in diagnosing and treating disease. MMP-9 belongs to the family of proteinases that are involved in cytoskeletal degradation, which is a crucial phase of cancer progression. In the present study, we analyzed the serum concentration of MMP-9 in oral cancer patients and tried to establish MMP-9 as a predictive biomarker for the progression of oral cancer.We also correlated the clinical, sociodemographic andbiochemical parameters with the serum concentration of MMP-9 in oral cancer patients. Serum was extracted from the blood sample of 38 oral cancer patients and was analyzed for the concentration of MMP-9 using sandwiched ELISA.Predesigned proforma was used to capture the clinical, sociodemographic and biochemical parameters. Unpaired t-test was used to compare two means, one way ANOVA was used to compare more than two means and Pearson's correlation was used to correlate the variables. The mean concentration of MMP-9 in patients of oral cancer was 816.9 ± 236.1ng/mL. The MMP-9 expression level was higher at advanced oral cancer stages than in the early stages. No significant difference in theMMP expression was found in terms ofsociodemographic risk factorand tumor site. MMP-9 exhibit significant negativecorrelation with the HDLand significantly positive correlation with the PTI. Rest of thebiochemical parametersdoes not exhibit significant correlation. The present study suggests that serum concentration of MMP-9 can be a predictive biomarker for the progression of oral cancer, which needs to be validated by performing further longitudinal cross-sectional studies by taking ample sample size.

Risk factor of elevated matrix metalloproteinase-3 gene expression in synovial fluid in knee osteoarthritis women.

Metalloproteinases-3 (MMP3) are the main enzymes involved in cartilage degradation. Several genetic and non-genetic factors can increase the expression of MMP3 in patients with osteoarthritis (OA). This study aims to analyze the risk factors associated with the expression of the MMP3 gene rs679620 fluid synovial knee OA patients. A cross-sectional study was conducted at the orthopedic polyclinic Arifin Achmad Riau Province and Ibn Sina Hospital in Pekanbaru City. Ninety women who experienced knee OA were taken as samples by consecutive sampling and then signed the informed consent. Data were obtained through interviews using a questionnaire about characteristics, followed by weight and height measurements. Interleukin-1 β (IL-1β) and Tumor Necrosis Factor (TNF-α) were examined from the synovial fluid using the enzyme-linked immunosorbent assay (ELISA) method. The Metalloproteinases-3 (MMP3) gene polymorphism rs679620 was obtained from the DNA analysis of joint fluid results in the Biomedical Laboratory of the Faculty of Medicine, Andalas University. The data was processed computerized and then analyzed using the correlation Spearman-Rank, and chi-square tests. The results of statistical analysis are considered significant if the p-value is 0.05. The MMP3 rs679620 gene polymorphism of the mutant type was 88.9%, with the same proportion of AG and GG alleles (44.4%). Subjects aged ≥ 60 years were 53.3%, 85.6% did not work and 84.4% had menopause. The highest degree of OA was grade 2 (53.3%), most of whom had a risky nutritional status (84.4%). The median expression of the MMP3 rs679620 gene was 5.28 copies number. There is a significant relationship between MMP3 gene polymorphism rs679620, age, IL-1β, and TNF-α with MMP3 gene expression rs679620. There is no significant relationship between BMI, work status, and menopausal status with MMP3 gene expression rs679620. Conclusion. MMP3 gene polymorphism rs679620, age, levels of IL-1β and TNF-α are risk factors for increased MMP3 gene rs679620 expression in female knee OA.

Анализ полиморфизма генов матричных металлопротеиназ ММР2, ММР3 и ММР9 среди российских европеоидных пациентов с первичной открытоугольной глаукомой

Relevance. Glaucoma is one of the significant causes of irreversible blindness among aging population around the world. The significant role of matrix metalloproteinases (MMPs) in the remodeling of eye structures during the development of glaucoma is widely discussed in the scientific literature. It is assumed that the polymorphism of the regulatory regions of the genes encoding MMP can affect the level of their expression and contribute to predisposition to the development of the disease. Purpose. To study the features of the polymorphism of the genes of matrix metalloproteinases MMP2, MMP3 and MMP9 in patients with primary open-angle glaucoma. Material and methods. Main group 99 patients with a verified diagnosis of stage II primary open-angle glaucoma. 100 people without glaucoma in anamnesis are included in the control group. Polymorphism of promoter region MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242) genes was analyzed. Results. It is shown that minor homozygous genotype MMP2 is significantly more frequent, and heterozygous genotypeMMP2is less frequent among patients with glaucoma. Two complex genotypes which associated with disease were identified. The protective MMP2-1306 TT genotype was confirmed at group of women with glaucoma relative to women without glaucoma and high odds ratio of disease developing for complex genotype MMP2-130 6TC:MMP3-1171 6A6A was shown relative to the general group. Conclusion. The data we obtained on the protective significance of the presence in the human genome of the homozygous variant of the MMP2gene -1306TTallow us to use them in further studies related to risk of occurrence and development of primary open-angle glaucoma. Key words: primary open-angle glaucoma, gene polymorphism, matrix metalloproteinases

Dynamics of matrix metalloproteinase 9 in comorbid patients who had myocardial infarction with ST elevation

Aim. The aim of the work was to study for three years the dynamics of matrix metalloproteinase 9 in patients with comorbid pathology who had suffered a myocardial infarction with ST segment elevation. Materials and methods. The study included patients of both sexes older than 18 years. All of them signed an informed consent for participation in the study. The inclusion criteria, in addition to signing informed consent for participation in the study, were acute myocardial infarction with ST elevation (STEMI), PCI and implantation of 1-2 stents into the left coronary artery, the presence of hypertension, type 2 diabetes melitus. Patients younger than 18 years and older than 80 years with type 1 diabetes mellitus, the presence of oncological diseases at the time of the study or in the anamnesis, chronic obstructive pulmonary disease, chronic viral infections were not included. All diagnoses were established according current clinical recommendations. The patients were divided into two groups. The first group included patients with arterial hypertension and type 2 diabetes mellitus, the second group included patients who had suffered acute myocardial infarction with ST segment elevation, who had arterial hypertension and type 2 diabetes mellitus. Serum was used to assess the content of matrix metalloproteinase 9. A standard test kit was used ("Cloud-Clone Corp.", China) in accordance with the instructions. The calculations were carried out using Excel spreadsheets and the statistical software package Statistica 10 (StatSoftInc.) USA. Results. When studying the level of metalloproteinase 9 for 3 years in patients who had suffered a myocardial infarction, it was found that the level of MMP-9 was statistically significantly higher in patients at the time of hospitalization, then decreased by the first year after the index event and became comparable with patients who did not have MI. After 36 months from the start of the study, patients who had suffered a myocardial infarction had statistically significantly higher levels of matrix metalloproteinase 9, compared with their values by the end of the first year, however, these data are comparable to the level of MMP-9 in patients of the first group. The level of MMP-9 in the first group is comparable at all time stages of observation. Conclusion. The inflammatory marker MMP-9, under certain conditions, can serve as a good predictor for predicting fatal outcomes and repeated AMI in patients who have undergone MI.

Serum Matrix Metalloproteinase-2: A Possible Link between COVID-19 and Periodontitis

Background: Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is a severe infection primarily targeting the respiratory system. However, many other extrapulmonary body organs are also
 affected with a varying degree of severity. Some evidence indicated the development of periodontist in patients, although the pathogenesis is not well-defined.
 Aims: This study aimed to investigate the association of COVID-19 severity and role of matrix metalloproteinase 2 in development of periodontitis.
 Patients and Methods: This is a cross sectional study which included a total of 160 patients with COVID-19. Patients were categorized into severe and mild-moderated according to World Health Organization criteria. Periodontitis was diagnosed in those patients according to clinical criteria. Serum level of matrix metalloproteinase 2 was estimated in all patients using enzyme linked immunosorbent assay (ELISA). Demographic and laboratory data were obtained from the patients’ records.
 Results: Forty-two patients (26.25%) had severe COVID-19. Demographically, older ages and the presence of comorbidities were significantly associated with COVID-19 severity. Besides the inflammatory markers, the median serum level of MMP-2 was higher in severe than mild-moderate COVID-19 cases (208.12 ng/ml vs. 196.33 ng/ml) with a significant difference. The PO rate in severe and mild-moderate COVID-19 was 23.81% and 10.17%, respectively, with a significant difference. The median serum MMP-2 in patients with PO was 228.5 ng/ml which was significantly higher than those without PO 193.81 ng/ml.
 Conclusions: These data indicate the significant association between COVID-19 severity and development of PO. Matrix metalloproteinase-2 could be the possible link between severe COVID-19 and PO.

Association of Zinc Status with Matrix Metalloproteinases, Advanced Glycation End-Products, and Blood Pressure in Patients with Chronic Kidney Disease.

Inflammation, oxidative stress, and hypertension trigger the development of chronic kidney disease (CKD). Zinc is known to have antioxidant and anti-inflammatory properties and a possible role in regulating blood pressure. The aim of this study was to investigate the correlation of serum zinc with matrix metalloproteinase-2 and-9 (MMP-2, MMP-9), advanced glycation end products (AGEs), and blood pressure in patients with CKD. This cross-sectional study included 90 patients with CKD. Serum zinc and the levels of MMP-2, MMP-9, AGEs, and creatinine were measured using validated biochemical methods. Three 24-h food recalls were completed to evaluate dietary zinc intake. Systolic and diastolic blood pressure (SBP, DBP) were measured using a digital sphygmomanometer. Participants' mean age was 60.68 ± 8.81years. The prevalence of zinc deficiency in our participants was 10%. Serum zinc was negatively correlated with MMP-9 (r = - 0.231, p = 0.032) and creatinine (r = - 0.304, p = 0.004). However, after adjusting for confounding variables, the association between serum zinc and MMP-9 was near the significance level (β = - 0.174, p = 0.09) and zinc remained in the model as one of the predictors. Serum zinc was positively correlated with the dietary intake of zinc (r = 0.241, p = 0.025) and estimated glomerular filtration rate (eGFR) (r = 0.259, p = 0.015). In conclusion, our results showed that serum zinc might be one of the predictors of serum MMP-9 in patients with CKD. In addition, serum zinc was positively associated with its dietary intake and eGFR. Future longitudinal studies or clinical trials are required to reveal any causal association between zinc status and profibrotic or inflammatory biomarkers among patients with CKD.

Диагностика синдрома активации макрофагов в зависимости от исходного уровня IL-6 у пациентов с новой коронавирусной инфекцией, вызванной вирусом SARS-CoV-2

An effect of the antiviral drug Kagocel on the levels of metalloproteinases MMP-8 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in induced sputum during treatment of community-acquired viral-bacterial pneumonia was analyzed. 60 adult patients with verified community-acquired pneumonia of viral-bacterial etiology were included in the follow-up monitoring.
 Materials and methods. All patients were randomly stratified into 2 groups: group 1 (comparison group) consisted of 30 patients receiving Ceftriaxone monotherapy; group 2 (main group) 30 subjects who were prescribed Ceftriaxone and the antiviral drug Kagocel as etiotropic treatment. Both groups were comparable in gender, age and time of admission to the hospital.
 Results. During hospitalization, patients in both groups had elevated levels of MMP-8, MMP-9, TIMP-1 and TIMP-2 in induced sputum compared to the reference values. By 7 days of inpatient treatment, the level of MMP-8 was still significantly higher than the reference values in both groups, being in patients from group 2 it decreased compared to baseline values, whereas in patients from group 1, on the contrary, it was markedly elevated. The activity of MMP-9 during hospitalization was also high in patients from both groups compared with its level in healthy subjects. By day 7 of therapy, changes in various parameters were recorded. The level of MMP-9 in patients from group 1 increased, whereas in group 2 on the contrary decreased. The level of TIMP-1 decreased in patients of the 1st group below the control value, and in patients of the 2nd group reached the reference values. The level of TIMP-2 decreased in both groups and reached that of in control group.
 Conclusion. Antiviral drug Kagocel being included in the standard antibacterial regimen of community-acquired viral-bacterial pneumonia reduces the level of MMR-9 and intensity in imbalance between MMP and TIMP parameters by 7 days of therapy, which leads to accelerated clinical recovery.