Serum MMP-9 Research Articles

Utility of Serum Matrix Metalloproteinase-7 as a Biomarker in Cholestatic Infants with Congenital Heart Disease.

Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH. This is a single-center cross-sectional study including infants < 180days of age with cholestasis and serum MMP-7 levels collected from 2019 to 2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test. A total of 149 patients were included. Patients with CHD had significantly elevated MMP-7 levels relative to the non-CHD cohort (50 vs. 34ng/mL, p = 0.009). Sub-analysis comparing infants with and without PH revealed significantly elevated median MMP-7 levels in those with clinically significant PH (125 vs. 39ng/mL, p = 0.010). CHD patients with PH had greater median MMP-7 compared to CHD patients without PH (154 vs 43ng/mL, p = 0.028). Serum MMP-7 levels in infants with congenital heart disease with cholestasis (CHD-C) were significantly elevated compared to those with cholestasis alone. MMP-7 may help identify non-BA cholestatic infants who have concurrent clinically significant pulmonary hypertension. Larger, prospective studies are needed to validate this finding and establish CHD-specific MMP-7 cut-offs.

Impact of anti-human IgG hinge peptide antibodies on identification of patients with early seronegative rheumatoid arthritis.

The early diagnosis of seronegative rheumatoid arthritis (SNRA), characterised by the absence of rheumatoid factor and anti-citrullinated antibody, involves a greater challenge compared to seropositive RA (SPRA). This study aimed to assess the discriminatory potential of anti-human IgG hinge antibodies (AHAs) for patients with early SNRA. DMARDs-naive patients with SPRA (n=43), SNRA (n=21), and non-RA (n=49), with disease duration < 2 years, were included. Antigens comprised IgG1 or IgG4 F(ab')2 cleaved by pepsin or MMP-3 and their hinge peptide analogues. Eight IgG anti-hinge antibodies (AHAs) against these antigens were measured in sera from the patients and 58 healthy controls (HCs) using ELISA. Serum CRP and MMP-3 levels, and clinical disease activity index (CDAI), were obtained from medical records. The area under the curve (AUC) obtained from logistic regression and receiver operating characteristic curve analyses were used as a discriminant indicator. The levels of the IgG AHAs were as follows: SPRA≥SNRA≈non-RA>HC. None of the AHAs were effective in discriminating SNRA from non-RA. However, the combination of MMP-3 and AHAs against IgG4 hinge peptide analogues demonstrated the utility (AUC=0.94). Furthermore, combination of MMP-3, AHAs against IgG1 hinge peptide analogues and CDAI maximally exerted discriminatory power (AUC=0.997). Specific AHAs in combination with MMP-3 and CDAI are potentially useful to discriminate SNRA from non-RA.

MMP-9 as a clinical marker for endometriosis: a meta-analysis and bioinformatics analysis.

This study systematically evaluated the potential efficacy of serum matrix metalloproteinase-9 (MMP-9) concentration as a diagnostic marker for endometriosis through meta-analysis. Early and accurate diagnosis of endometriosis, a common gynecological disease, is crucial for improving patient prognosis. Hence, this study aimed to comprehensively analyze the data from multiple studies to assess the diagnostic value of serum MMP-9 concentration for endometriosis. Articles investigating the association between MMP-9 and endometriosis, published from the inception of the databases until February 2024, were systematically retrieved from multiple databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and CNKI. Download and analyze the GSE7305, GSE23339, and GSE51981 datasets. Statistical analyses of all eligible studies were conducted using RevMan 5.4, Stata 11.0, and R software version 4.3.3. Fifteen studies fully met the inclusion criteria for the meta-analysis. The concentration of MMP-9 in the blood of patients with endometriosis was significantly higher compared to that of the control group (p < 0.0001). Subgroup analysis based on different stages of endometriosis revealed a trend towards significantly higher serum MMP-9 concentrations in patients, whether in stages I-II or III-IV. Bioinformatics analysis revealed differences in the expression of MMP-9 in endometrial tissue between EMT patients and healthy controls in the GSE7305 and GSE23339 datasets. Additionally, in the GSE51981 dataset, we found significant differences between the normal group and both mild and severe cases of endometriosis. Both the current meta-analysis and bioinformatics analysis indicate differences in MMP-9 concentration levels between endometriosis patients and healthy individuals, with potentially elevated MMP-9 concentrations in serum samples from patients with endometriosis. https://www.crd.york.ac.uk/prospero, identifier CRD42024525864.

Utility of Serum Matrix Metalloproteinase-7 as a Biomarker in Cholestatic Infants with Congenital Heart Disease.

Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH. This is a single center cross sectional study including infants <180 days of age with cholestasis and serum MMP-7 levels collected from 2019-2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test. A total of 149 patients were included. Patients with CHD had significantly elevated MMP-7 levels relative to the non-CHD cohort (50 vs. 34 ng/mL, p=0.009). Sub-analysis comparing infants with and without PH revealed significantly elevated median MMP-7 levels in those with clinically significant PH (125 vs. 39 ng/mL, p=0.010). CHD patients with PH had greater median MMP-7 compared to CHD patients without PH (154 vs 43 ng/mL, p=0.028). Serum MMP-7 levels in infants with CHD-C were significantly elevated compared to those with cholestasis alone. MMP-7 may help identify non-BA cholestatic infants who have concurrent clinically significant pulmonary hypertension. Larger, prospective studies are needed to validate this finding and establish CHD-specific MMP-7 cutoffs.

Retraction Note: optical imaging medical diagnosis and analysis of drug treatment for endometriosis and the impact of serum VEGF and MMP-9

Retraction Note: optical imaging medical diagnosis and analysis of drug treatment for endometriosis and the impact of serum VEGF and MMP-9

Interaction of MMP-9 in the active phase of Graves' disease with and without ophthalmopathy.

Thyroid eye disease (TED) is expressed as orbital inflammation, and serum levels of several proinflammatory cytokines have been studied among patients with Graves' disease (GD) with and without TED; however, a more sensitive and specific marker for the different phases of GD and TED is still lacking. Seventeen active TED, 16 inactive TED, 16 GD without TED, and 16 healthy controls were recruited. Serum IL-17A, MMP-2, MMP-3, and MMP-9 were measured by multiplex bead assay. TED hormone and eye parameters were evaluated, and their relationship with cytokine levels was analyzed. Serum MMP-9 was higher in active TED than healthy controls, whereas IL-17A was lower among these patients than in GD without TED and healthy controls. No differences were found in MMP-3 and MMP-2 concentrations. MMP-9 levels were lower in patients with inactive TED who underwent radioactive iodine (RAI) therapy and those on levothyroxine replacement. MMP-9 levels were elevated in patients on methimazole. A negative correlation was found between age at assessment and time of follow-up with MMP-9 levels in inactive TED. Free T3 and ophthalmometry values were positively correlated with MMP-9 in the GD without TED and inactive TED groups, respectively. In conclusion, serum MMP-9 was increased in patients with active TED and was related to the RAI treatment, longer follow-up time, and higher ophthalmometry in patients with inactive TED, as well as thyroid function in GD without TED. MMP-9 may be involved in both the active phase of TED and the active phase of inflammation related to GD.NEW & NOTEWORTHY Our study addresses clinical aspects of specific ophthalmological examination and serum cytokine concentrations of patients with Graves' disease (GD) with and without ophthalmopathy. Our findings suggest that MMP-9 may be involved in the active phase of ophthalmopathy and in the active phase of GD. The central question is whether MMP-9 is a potential target for future treatments.

Circulating Matrix Metalloproteinases for Prediction of Aortic Dilatation in Children with Bicuspid Aortic Valve: A Single-Center, Observational Study

Circulating biomarkers have been proposed for early identification of aortic dilatation progression associated with bicuspid aortic valve (BAV), but matrix metalloproteinases (MMPs) are distinguished as signatures of increased extracellular matrix degradation, a landmark of aneurysm formation. The current study aims to identify the role of MMP-1, MMP-2, MMP-9, and the MMP inhibitor, TIMP-1, in identifying aortic dilation in children with BAV. We conducted a study on 73 children divided into two study groups, depending on the presence of aortic dilatation (group 1–43 BAV controls and group 2–30 children with BAV and aortic dilatation). Each patient underwent a cardiac ultrasound and, in each case, serum MMP-1, MMP-2, MMP-9, and TIMP-1 were quantified using xMAP technology. Comparison of the MMPs between the two study groups revealed significantly higher values only in the case of TIMP-1, among BAV controls. Moreover, the same TIMP-1 inversely correlated with aortic annulus absolute size and z score, as well as with ascending aorta z score. No particular correlation between the aortic phenotype and the presence of aortic dilatation was found. Future longitudinal research starting at pediatric ages could show the significance of MMPs screening in BAV individuals as predictors of aortic aneurysm formation.

Levels of Matrix Metalloproteinase-9 (MMP-9) and its gene polymorphism of Hydatid Cyst Disease in an Infected Patients

Hydatid cystic disease is an economic burden in Iraq since it decreases the productivity of sheep, goats, cows, and camels by making the organs unpalpable for human consumption, hence weight-loss and ill health. This is one of the most common zoonosis diseases shared between human beings and animals and appears in man hosts inlcuded some organes, such as liver and lung as hydatid cyst . it causes many complications that may lead to death in repured parasites. Now there are no safe and effective in the fight against this parasite, and the search for such medications is in research. The Matrix Metalloproteinase-9 is a one of the enzymes that belong to the family of matrix metalloproteinases (MMPs), which play a crucial role in the proteolytic degradation of the extracellular matrix (ECM). These enzymes have a zinc ion in the active site that is important for their proteolytic activity. MMP-9, also known as Gelatinase B, catalyzes gelatin and degrades components of the ECM, including abundant type IV collagen in basement membranes. MMP-9 plays an important role in various biological processes, including tissue remodeling, angiogenesis, and tissue inflammation. The objective of the study is to determine the impact of MMP-9 serum levels and specific single nucleotide polymorphisms (SNPs) rs17576 and rs76070157 on patients with hydatid disease, in comparison to a control group of healthy individuals. A total of (62) patients diagnosed with hydatid disease, consisting of 18 males and 44 females, were compared to a control group of(75) individuals, comprising 29 males and 46 females .The study examined the MMP-9 rs17576 and rs76070157 )SNPs( in patients with hydatid disease, comparing them to a control group of healthy individuals. The study revealed no statistically significant difference in the average age between the two groups at a significance level of 0.05. Additionally, the study found higher concentrations of MMP-9 in the sera of the infected group (20.40 ± 1.52 pg/µl) compared to the control group (19.49 ± 1.62 pg/µl). The rs17576 )SNPs( data indicated that the TT genotype and T allele exhibited a slightly higher frequency percentage in the group of patients with hydatid disease compared to the healthy group, however this difference was not statistically significant. The values are (98.4% and 99.0%) the value of pc is 0.001. The elevated odds ratio (OR) associated with the TT genotype and T allele may serve as a potential risk factor for hydatid disease. The rs17576 SNPs displayed genotypes that were not in accordance with Hardy-Weinberg equilibrium. However, these genotypes were consistent with those observed in a control group. The GG genotype showed a significant increase in frequency compared to the control group (100.0% vs. 100.0%), while the G allele exhibited a non-significant increase in frequency. The odds ratio (OR) for the TG genotype was 3.68, and the p-value (pc) was 0.05.Elevated value could potentially increase the risk of hydatid disease. The presence of the TG genotype was shown to considerably increase the frequency percentage in the group of patients with hydatid disease. The odds ratio (OR) value of 1.6 suggests that it may be a risk factor for hydatid disease, with a frequency of 98.4% compared to 0.99 % in the control group. The p-value of 0.001 indicates a statistically significant association. The GG genotype was present in (0%) of the affected group but absent (100.0%) in the healthy group. The odds ratio (OR) of 3.68, with a p-value of 0.001, suggests that the GG genotype is associated with a significantly lower risk of hydatid disease.

Serum matrix metalloproteinase-7, Syndecan-1, and CA 19-9 as a biomarker panel for diagnosis of pancreatic ductal adenocarcinoma.

Matrix metalloproteinase-7 (MMP-7) and Syndecan-1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts. In this case-control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups. Serum MMP-7 and SDC1 were measured by ELISA. The diagnostic accuracy of their levels for diagnosing PDAC and pancreatic cysts was computed, and their association with survival outcomes was evaluated. MMP-7 median serum levels were significantly elevated in the PDAC (7.3 ng/mL) and cyst groups (3.7 ng/mL) compared with controls (2.9 ng/mL) (p < 0.001 and 0.02, respectively), and also between the PDAC and cyst groups (p < 0.001), while SDC1 median serum levels were significantly elevated in PDAC (43.3 ng/mL) compared with either cysts (30.1 ng/mL, p < 0.001) or controls (31.2 ng/mL, p < 0.001). The receiver operating characteristic curve analysis area under the curve in PDAC versus controls was 0.90 and 0.78 for MMP-7 and SDC1, respectively, while it was 1.0 for the combination of the two and CA 19-9 (p < 0.001). The combination of the three biomarkers had a perfect sensitivity (100%). Due to its high sensitivity, this biomarker panel has the potential to rule out PDAC in suspected cases.

Candidate Biomarkers For Response To Treatment In Psoriatic Disease.

To determine whether biologic therapy alters serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in psoriatic arthritis (PsA) and psoriasis (PsC) patients, and whether baseline levels of these proteins predict response to treatment for PsA. We included PsA patients on TNF inhibitors (TNFi), Interleukin-17 inhibitors (IL-17i), methotrexate (MTX), and untreated with bDMARDs or csDMARDs (untreated) and PsC patients on bDMARDs and matched untreated. Serum samples at baseline and 3-6 months follow-up were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as: 1. Achieving low disease activity or remission (according to DAPSA), 2. 75% reduction in PASI, and 3. 50% reduction in actively inflamed joint count. In PsA, TNFi reduced serum levels of all five proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA (p<0.05). There were no significant differences between treated or untreated PsC patients. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (AUC>0.8) for response to biologics in PsA patients. Biologics treatment and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in PsA patients. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.

Dietary Zn proteinate with moderate chelation strength alleviates heat stress-induced intestinal barrier function damage by promoting expression of tight junction proteins via the A20/NF-κB p65/MMP-2 pathway in the jejunum of broilers

BackgroundThe aim of this study was to determine whether and how Zn proteinate with moderate chelation strength (Zn-Prot M) can alleviate heat stress (HS)-induced intestinal barrier function damage of broilers. A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers. Under high temperature (HT), a 1 (Control, HT-CON) + 2 (Zn source) × 2 (added Zn level) factorial arrangement of treatments was used. The 2 added Zn sources were Zn-Prot M and Zn sulfate (ZnS), and the 2 added Zn levels were 30 and 60 mg/kg. Under normal temperature (NT), a CON group (NT-CON) and pair-fed group (NT-PF) were included.ResultsThe results showed that HS significantly reduced mRNA and protein expression levels of claudin-1, occludin, junctional adhesion molecule-A (JAMA), zonula occludens-1 (ZO-1) and zinc finger protein A20 (A20) in the jejunum, and HS also remarkably increased serum fluorescein isothiocyanate dextran (FITC-D), endotoxin and interleukin (IL)-1β contents, serum diamine oxidase (DAO) and matrix metalloproteinase (MMP)-2 activities, nuclear factor kappa-B (NF-κB) p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum. However, dietary supplementation with Zn, especially organic Zn as Zn-Prot M at 60 mg/kg, significantly decreased serum FITC-D, endotoxin and IL-1β contents, serum DAO and MMP-2 activities, NF-κB p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers, and notably promoted mRNA and protein expression levels of claudin-1, ZO-1 and A20.ConclusionsOur results suggest that dietary Zn, especially 60 mg Zn/kg as Zn-Prot M, can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.

The Effect of Salmon Calcitonin Adjuvant Treatment for Lumbar Spine Fracture: A Prospective, Randomized, Controlled Trial.

The study aimed at analyzing the therapeutic effect of salmon calcitonin on patients with lumbar spine fracture after operation. Eighty-eight cases with lumbar spine fracture who underwent percutaneous vertebroplasty (PVP) in The Huichang People's Hospital from February 2020 to February 2023 were separated into two groups. The 44 cases in the control group were treated with calcium carbonate and Vitamin D3 tablets, on the basis, the salmon calcitonin was applied to treat the 44 cases in study group. The pain degree, bone metabolism index and matrix metalloproteinase levels were determined and compared between two groups. Lumbar function and daily living activity ability in two groups were evaluated, and adverse reactions during treatment were observed. The pain degree in study group was alleviated after treatment for 3 mo compared with the control group (p<0.05). The bone specific alkaline phosphatase (BALP) and osteocalcin (OC) levels were increased, while beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) levels were decreased in study group after treatment for 3 mo compared with control group (p<0.05). After treatment for 3 mo, the serum matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) levels in study group were lower than those in control group (p<0.05). Three months after treatment, the Oswestry Disability Index (ODI) score was lower and Barthel Index (BI) score was higher in study group than those of control group (p<0.05). No severe adverse reactions were observed in both groups during treatment (p>0.05). Salmon calcitonin can relieve the pain degree, improve the levels of bone metabolism and matrix metalloproteinase, and improve the lumbar spine function and ability of daily living activity in patients with lumbar spine fracture.

Virtual screening reveals fluorescent probes for detecting Pan-Zinc center activity in serum MMPs: A potential biomarker for early tumor screening

Early tumor screening is pivotal for enhancing tumor treatment efficacy and patient survival rates, yet identifying reliable biomarkers for early detection remains a challenge. Previous studies have explored different isoforms of matrix metalloproteinases (MMPs) in serum for their predictive value in tumor, but their results have been inconsistent. Herein, we introduce a novel fluorescent probe, C9 (N-oxide-8-hydroxyquinoline-5-sulfonic acid), designed to specifically label the pan zinc center activity of MMPs (PZCA-MMPs), which in a sense represents the overall MMPs activity in serum. The rational design of fluorescent probe C9 is based on its ability to bind the zinc ions in the structure of MMPs, facilitated by the oxides on hydroxyl (–OH) and nitro oxide (N→O) groups present in C9, as supported by theoretical calculations such as Gaussian and Schrödinger. Experimental validation confirmed its efficacy for detecting PZCA-MMPs in vitro and for fluorescence imaging of MMPs’ zinc ions in cellular contexts, validated through absolute integrated fluorescence intensity measurements at 510 nm. We also demonstrated through in vitro fluorescent analysis that neither metal ions nor abundant serum proteins such as albumin (BSA) and other metalloproteins interfere with the signal response of C9. Notably, in comparative analysis of serum samples from healthy controls and breast tumor patients, PZCA-MMPs showed a highly discriminatory area under the ROC curve (AUC) of 0.9377, surpassing established tumor biomarkers such as CA125, CA15-3, CA19-9, and CA72-4. In particular, for tumor patients, PZCA-MMPs can effectively distinguish between metastatic and non-metastatic patients (*P<0.05). Therefore, this provides a potential alternative biomarker for tumor screening. Future studies aim to further elucidate the clinical utility of PZCA-MMPs using a broader spectrum of clinical samples.

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.

Expression of Matrix Metalloproteinase-3 in the Aqueous Humor of Patients with Posner-Schlossman Syndrome

Purpose To explore the expression of matrix metalloproteinase-3 (MMP-3) in the aqueous humor of patients with Posner-Schlossman syndrome (PSS), and the association between MMP-3 and PSS. Methods Peripheral blood and aqueous humor were routinely collected from 29 patients with PSS (PSS group) and 30 patients with age-related-cataract (ARC) (control group). The content of MMP-3 in serum and aqueous humor was measured by immunoturbidimetry. The correlation between MMP-3 and ophthalmic examination results were verified by Spearman’s correlation analysis. Results The MMP-3 level in the aqueous humor of the PSS group was (25.86 ± 13.4)ng/ml, significantly higher than that in the control group (3.9 ± 2.7)ng/ml(p < 0.001), while there was no significant difference in serum MMP-3 level between the two groups (p = 0.125). The endothelial cell density (ECD) in the aqueous humor of the PSS group was (2078 ± 440) cell/mm2, intraocular pressure (IOP) in the aqueous humor of the PSS group was (33 ± 12) mmHg. The correlation analysis of aqueous humor MMP-3 and various ophthalmic examination results showed that aqueous humor MMP-3 had a moderate correlation with IOP and the difference in ECD between the affected eye and the fellow eye. Conclusions MMP-3 level is elevated in the aqueous humor of PSS patients, and it may play an important role in the pathogenesis of PSS.

Level of some matrix metalloproteinases in blood serum in relation to their genetic polymorphism depending on age

The article presents data on the state of the proteolysis system and genes for the regulation of matrix metalloproteinases in 180 conditionally healthy women and men of young, middle, elderly and senile ages. A single sampling of the material (buccal epithelium) was performed in patients. PCR examination of the buccal epithelium for the analysis of polymorphisms of the genes MMP-1 rs1799750 and MMP-3 rs 3025058 was carried out on the instrument base of the DNA amplifier Bio-Rad CFX96. Serum levels of MMP-1, MMP-3 were studied by the sandwich variant of solid-phase enzyme immunoassay. Statistical processing of the obtained results was carried out using the IBM SPSS Statistics 26 program using nonparametric statistics methods. The results of the study. The values of MMP-1 and MMP-3 in the group of conditionally healthy women at a young age were lower than the values of middle age, whereas in old age their serum levels varied in different directions: MMP-1 decreased, and MMP-3 increased. When analyzing polymorphisms of the MMP-1 rs1799750 gene, the homozygous genotype -/- with low expression of the MMP-1 gene prevailed in young and middle-aged women, and in women over 75 years of age, the carriage of the G/G homozygote with active gene expression was recorded. When evaluating the expression of the MMP-3 rs 3025058 gene, it was found that young women significantly more often had 5A/5A polymorphism with high gene activity, but with a lower level of MMP- 3. In middle and old age, 65% have a heterozygous 5A/6A allele with reduced gene expression activity. In conditionally healthy men, the level of MMP-1 in blood serum increased in the middle-aged and senile groups, the values of MMP-3 in the group under 45 years of age were low compared with the elderly group (p = 0.041). MMP-1 rs1799750 in men under 75 years of age was identified in the -/G variant in the majority. Homozygous polymorphism of the MMP-3 rs 3025058 5A/5A gene with high activity of MMP-3 prevailed in groups of men under 60 years of age with serum levels of MMP-3 100.2 ng/mL and 92.5 ng/mL, respectively.

Salivary and serum inflammatory biomarkers during periodontitis progression and after treatment.

To identify serum- and salivary-derived inflammatory biomarkers of periodontitis progression and determine their response to non-surgical treatment. Periodontally healthy (H; n = 113) and periodontitis patients (P; n = 302) were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6 months after non-surgical periodontal therapy (NSPT). Participants were classified according to disease progression: P0 (no sites progressed; P1: 1-2 sites progressed; P2: 3 or more sites progressed). Ten salivary and five serum biomarkers were measured using Luminex. Log-transformed levels were compared over time according to baseline diagnosis, progression trajectory and after NSPT. Significant differences were sought using linear mixed models. P2 presented higher levels (p < .05) of salivary IFNγ, IL-6, VEGF, IL-1β, MMP-8, IL-10 and OPG over time. Serum analytes were not associated with progression. NSPT led to clinical improvement and significant reduction of IFNγ, IL-6, IL-8, IL-1β, MMP-8, IL-10, OPG and MMP-9 in saliva and of CRP, MMP-8, MMP-9 and MPO in serum. Periodontitis progression results from a sustained pro-inflammatory milieu that is reflected in salivary biomarkers, but less so in serum, likely because of the limited amount of progression per patient. NSPT can significantly decrease the levels of several salivary analytes.

Diagnostic and Prognostic Role of Circulating microRNAs in Patients with Coronary Artery Disease-Impact on Left Ventricle and Arterial Function.

Recent studies reported that circulating microRNAs (miRNAs) can target different metalloproteases (MMPs) involved in matrix remodeling and plaque vulnerability. Consequently, they might have a role in the diagnosis and prognosis of coronary artery disease. To quantify circulating miRNAs (miRNA126, miRNA146, and miRNA21) suggested to have possible cardiovascular implications, as well as levels of MMP-1 and MMP-9, and to determine their association with left ventricular (LV) function and with arterial function, in patients with either ST-segment elevation acute myocardial infarction (STEMI) or stable ischemic heart disease (SIHD). A total of 90 patients with coronary artery disease (61% men, 58 ± 12 years), including 60 patients with STEMI and 30 patients with SIHD, were assessed within 24 h of admission, by measuring serum microRNAs, and serum MMP-1 and MMP-9. LV function was assessed by measuring ejection fraction (EF) by 2D and 3D echocardiography, and global longitudinal strain (GLS) by speckle tracking. Arterial function was assessed by echo tracking, CAVI, and peripheral Doppler. Circulating levels of miRNA146, miRNA21, and MMP1 were significantly increased in patients with STEMI vs. SIHD (p = 0.0001, p = 0.0001, p = 0.04, respectively). MiRNA126 negatively correlated with LVEF (r = -0.33, p = 0.01) and LV deformation parameters (r = -0.31, p = 0.03) in patients with STEMI and negatively correlated with ABI parameters (r = -0.39, p = 0.03, r = -0.40, p = 0.03, respectively) in patients with SIHD. MiRNA146 did not have any significant correlations, while higher values of miRNA21 were associated with lower values of GLS in STEMI patients and with higher values of GLS in SIHD patients. Both MMP1 and MMP9 correlated negatively with LVEF (r = -0.27, p = 0.04, r = -0.40, p = 0.001, respectively) and GLS in patients with STEMI, and positively with arterial stiffness in patients with SIHD (r = 0.40 and r = 0.32, respectively; both p < 0.05). MiRNA126, miRNA21, and both MMP1 and MMP9 are associated with LV and arterial function parameters in patients with acute coronary syndrome. Meanwhile, they inversely correlate with arterial function in patients with chronic atherosclerotic disease. However, further studies are needed to establish whether these novel biomarkers have diagnosis and prognosis significance.

NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9.

Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Correlation between matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 and white matter hyperintensities in patients with cerebral small vessel disease based on cranial magnetic resonance 3D imaging

ObjectiveThe objective of this study was to investigate the correlation between serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels and their ratios with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD). MethodsThis cross-sectional study was done on a prospective cohort of patients with CSVD. Qualitative and quantitative analyses of WMHs were performed using Fazekas grading and lesion prediction algorithm (LPA) methods. Biomarkers MMP-2, MMP-9, and TIMP-1 were measured to explore their correlation with the severity of WMHs. ResultsThe sample consisted of 144 patients with CSVD. There were 63 male and 81 female patients, with an average age of 67.604 ± 8.727 years. Among these, 58.33% presented with white matter hyperintensities at Fazekas grading level 1, with an average total template volume of WMHs of 4.305 mL. MMP-2 (P = 0.025), MMP-9 (P = 0.008), TIMP-1 (P = 0.026), and age (P = 0.007) were identified as independent correlates of WMHs based on Fazekas grading. Independent correlates of the total template volume of WMHs included MMP-2 (P = 0.023), TIMP-1 (P = 0.046), age (P = 0.047), systolic blood pressure (P = 0.047), and homocysteine (Hcy) (P = 0.014). In addition, age (P = 0.003; P < 0.001), interleukin-6 (IL-6) (P < 0.001; P = 0.044), Hcy (P < 0.001; P < 0.001), glycated hemoglobin (HbA1c) (P = 0.016; P = 0.043), and chronic kidney disease (P < 0.001; P < 0.001) were associated with both WMHs Fazekas grading and the total template volume of WMHs. ConclusionSerum levels of MMP-9, MMP-2, and TIMP-1 were independently associated with the Fazekas grading, while serum TIMP-1 and MMP-2 levels were independently related to the total template volume of WMHs. The association of TIMP-1 and MMP-2 with the severity of CSVD-related WMHs suggests their potential role as disease-related biomarkers. However, further research is required to uncover the specific mechanisms underlying these interactions.