Higher Matrix Metalloproteinase-9 Research Articles

MMP2hi Fibroblasts Regulate CD8+ T Cell Residency and Inflammation via CD100 in Psoriasis.

Psoriasis, a T cell-mediated chronic inflammatory skin condition, is characterized by the interaction of T cells with various cell types, forming an inflammatory microenvironment that sustains psoriatic inflammation. The homeostasis of these tissue-resident T cells are supported by fibroblasts, the primary structural cells in the dermis. In psoriasis, there is an increased expression of matrix metalloproteinase 2 (MMP2), mediating the structural alterations of skin tissues and the modulation of inflammation. Additionally, the CD100-PLXNB2 axis is known to enhance psoriasis inflammation via keratinocytes, and CD103 levels are associated with the severity of psoriasis upon relapse. To elucidate the role of fibroblasts and the MMP2/CD100 axis in modulating psoriasis inflammation. CD100 expression and function in psoriasis were assessed using immunofluorescence, ELISA, single-cell transcriptome sequencing, cellular interaction analyses, and qRT-PCR. CD8+ T cells from psoriasis patients were isolated using magnetic beads to investigate the regulatory effect of MMP2 on CD100 expression on their membranes. Single-cell transcriptome sequencing, spatial transcriptome sequencing, mimetic timing analysis, immunofluorescence, and flow cytometry were utilized to determine the origin of MMP2 and its impact on CD103+CD8+ T cells. The hypotheses were further validated in vivo using MMP2 and CD100 inhibitors. Soluble CD100 (sCD100) was significantly upregulated in both psoriatic lesions and peripheral blood, amplifying psoriasis inflammation by promoting the production of inflammatory cytokines by keratinocytes, fibroblasts, and endothelial cells through the sCD100-PLXNB2 axis. Fibroblasts with high MMP2 expression (MMP2hi) exacerbate psoriasis symptoms by facilitating CD100 shedding from CD8+ T cell membranes. Additionally, it was demonstrated that fibroblasts enhance the upregulation of the CD8+ T cell residency factor CD103 in co-cultures with CD8+ T cells. Inhibitors targeting MMP2 and CD100 proved effective in reducing inflammation in a model of imiquimod-induced psoriasis. Our findings underscore the pivotal role of MMP2hi fibroblasts in the amplification and recurrence of inflammatory responses in psoriasis. These fibroblasts augment psoriasis inflammation through the CD100-PLXNB2 axis by facilitating CD100 shedding on CD8+ T cell membranes and by upregulating CD103, thereby enhancing CD8+ T cell residency.

Correlation of serum matrix metalloproteinase 3 with osteoporosis in patients of postmenopausal rheumatoid arthritis

Osteoporosis (OP) is a common complication of postmenopausal women with rheumatoid arthritis (RA). Herein, the objective of our study was to explore the correlation between serum matrix metalloproteinase 3 (MMP3) and OP among postmenopausal women with RA to foster better diagnosis and treatment. A total of 208 elderly postmenopausal women with RA were included in this study, with 83 patients diagnosed with OP after RA diagnosis and 125 patients without OP. Serum MMP3 levels and bone mineral density (BMD) were measured and compared. The predictive value of serum MMP3 for OP in this population was also analyzed using receiver operating curve (ROC) analysis. Postmenopausal women with RA and OP diagnosis had markedly higher serum MMP3 levels, compared to those without OP. ROC analysis showed that serum MMP3 had predictive value for OP. Additionally, a negative correlation was observed between serum MMP3 levels and BMD. High serum MMP3 levels were also found to be associated with high abnormal bone metabolism. We found that serum MMP3 levels are strongly correlated with OP in postmenopausal women with RA and that elevated levels of serum MMP3 are linked to low BMD and high abnormal bone metabolism. Serum MMP3 may be a useful biomarker for predicting OP in this population, and could potentially aid in the development of targeted prevention and treatment strategies.

Inhibition of Metalloproteinases Extends Longevity and Function of In Vitro Human iPSC-Derived Skeletal Muscle.

In vitro culture longevity has long been a concern for disease modeling and drug testing when using contractable cells. The dynamic nature of certain cells, such as skeletal muscle, contributes to cell surface release, which limits the system's ability to conduct long-term studies. This study hypothesized that regulating the extracellular matrix (ECM) dynamics should be able to prolong cell attachment on a culture surface. Human induced pluripotent stem cell (iPSC)-derived skeletal muscle (SKM) culture was utilized to test this hypothesis due to its forceful contractions in mature muscle culture, which can cause cell detachment. By specifically inhibiting matrix metalloproteinases (MMPs) that work to digest components of the ECM, it was shown that the SKM culture remained adhered for longer periods of time, up to 80 days. Functional testing of myofibers indicated that cells treated with the MMP inhibitors, tempol, and doxycycline, displayed a significantly reduced fatigue index, although the fidelity was not affected, while those treated with the MMP inducer, PMA, indicated a premature detachment and increased fatigue index. The MMP-modulating activity by the inhibitors and inducer was further validated by gel zymography analysis, where the MMP inhibitor showed minimally active MMPs, while the inducer-treated cells indicated high MMP activity. These data support the hypotheses that regulating the ECM dynamics can help maximize in vitro myotube longevity. This proof-of-principle strategy would benefit the modeling of diseases that require a long time to develop and the evaluation of chronic effects of potential therapeutics.

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis

BackgroundBronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. MethodsThis study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. ResultsThe current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

Matrix metalloproteinase-1 serum level in association with the occurrence of striae distensae

Introduction: Striae distensae are fine atrophic scar tissue on the skin. They are formed on areas with dermal collagen rupture due to excessive stretching of the skin. Matrix metalloproteinase-1 (MMP-1) is an enzyme that degrades collagen types I and III. An imbalance in the expression of MMP-1 and transforming growth factor-beta (TGF-β), cytokine that trigger the synthesis of new collagen, leads to imperfect dermis remodeling process in atrophic scar tissue, which is a clinical appearance of striae distensae. This study aimed to determine the association between serum MMP-1 level and striae distensae. Methods: We conducted an observational cross-sectional study on 40 females with striae distensae and 40 controls. History taking, physical and dermatological examination, followed by blood sampling analysis of serum MMP-1 level with ELISA method were conducted in all subjects. Results: The mean serum MMP-1 levels in the striae distensae group were 51.54±28.03 ng/dL. All subjects in the striae distensae group had striae albae and only 7 subjects (17.5%) had striae rubrae. The most common location of striae distensae is the combination of femoral and gluteus regions (25%). The results of this study showed a relationship between high MMP-1 levels and the risk of striae distensae by 4.89 times (p = 0.002). Conclusion: There was an association between serum MMP-1 levels and striae distensae.

Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis

The liver is a common site of cancer metastasis, most commonly from colorectal cancer, and primary liver cancers that have metastasized are associated with poor outcomes. The underlying mechanisms by which the liver defends against these processes are largely unknown. Prohibitin 1 (PHB1) and methionine adenosyltransferase 1A (MAT1A) are highly expressed in the liver. They positively regulate each other and their deletion results in primary liver cancer. Here we investigated their roles in primary and secondary liver cancer metastasis. We identified common target genes of PHB1 and MAT1A using a metastasis array, and measured promoter activity and transcription factor binding using luciferase reporter assays and chromatin immunoprecipitation, respectively. We examined how PHB1 or MAT1A loss promotes liver cancer metastasis and whether their loss sensitizes to colorectal liver metastasis (CRLM). Matrix metalloproteinase-7 (MMP-7) is a common target of MAT1A and PHB1 and its induction is responsible for increased migration and invasion when MAT1A or PHB1 is silenced. Mechanistically, PHB1 and MAT1A negatively regulate MMP7 promoter activity via an AP-1 site by repressing the MAFG-FOSB complex. Loss of MAT1A or PHB1 also increased MMP-7 in extracellular vesicles, which were internalized by colon and pancreatic cancer cells to enhance their oncogenicity. Low hepatic MAT1A or PHB1 expression sensitized to CRLM, but not if endogenous hepatic MMP-7 was knocked down first, which lowered CD4+ T cells while increasing CD8+ T cells in the tumor microenvironment. Hepatocytes co-cultured with colorectal cancer cells express less MAT1A/PHB1 but more MMP-7. Consistently, CRLM raised distant hepatocytes' MMP-7 expression in mice and humans. We have identified a PHB1/MAT1A-MAFG/FOSB-MMP-7 axis that controls primary liver cancer metastasis and sensitization to CRLM. Primary and secondary liver cancer metastasis is associated with poor outcomes but whether the liver has underlying defense mechanism(s) against metastasis is unknown. Here we examined the hypothesis that hepatic prohibitin 1 (PHB1) and methionine adenosyltransferase 1A (MAT1A) cooperate to defend the liver against metastasis. Our studies found PHB1 and MAT1A form a complex that suppresses matrix metalloproteinase-7 (MMP-7) at the transcriptional level and loss of either PHB1 or MAT1A sensitizes the liver to metastasis via MMP-7 induction. Strategies that target the PHB1/MAT1A-MMP-7 axis may be a promising approach for the treatment of primary and secondary liver cancer metastasis.

4-Year Pulp Survival in a Randomized Trial on Direct Pulp Capping

IntroductionThis study aimed to assess pulp survival in a randomized trial on pulp lavage in adult nonpainful posterior teeth with carious pulp exposure. The treatment included complete caries excavation, direct pulp capping with mineral trioxide aggregate, and immediate restoration with composite resin. MethodsFluid was collected from the pulp wound to assess matrix metalloproteinase-9 (MMP-9) and total protein values. Before pulp capping, cavities were randomly (block randomization, n = 48) washed with a physiological saline or a sodium hypochlorite solution (2.5% NaOCl). Treatment outcome was assessed clinically (cold test) and radiographically after at least 1 year and again after at least 3 years. Painful failures were differentiated from nonpainful failures. Pulp survival was estimated using the Kaplan-Meier method including 95% confidence intervals (CIs) up to 1500 days. ResultsFrom the 96 patients originally enrolled, 73 individuals could be followed continuously. The clinical observations indicated a beneficial and sustained effect of pulp lavage with 2.5% NaOCl over a control treatment with physiological saline solution on estimated pulp survival 1500 days postintervention, with 7% (95% CI, 1%–40%) in the saline group versus 55% (95% CI, 30%–100%) in the NaOCl group. High MMP-9/total protein values in pulpal fluid collected from the exposed site indicated early and painful treatment failures yet were not associated with failures that occurred more than 250 days after intervention. ConclusionsThe low 4-year success rates reported here challenge the concept of direct pulp capping in the cases that were included. NaOCl lavage did not only increase the survival of affected pulps substantially but also particularly diminished painful failures (33% in the NaOCl group vs 62% in the saline group). The lack of the predictive value of MMP-9 assessments beyond early treatment failures points to inflammatory states of the pulp tissue under deep caries, which are not related to neutrophil infiltration.

Prediction of maternal and foetal outcomes among patients with preeclampsia using circulatory biomarkers (MMP-9 & ST2) - A prospective cohort study

IntroductionPreeclampsia is one of the major causes of maternal and foetal morbidity and mortality worldwide. Its complications include but are not limited to eclampsia, intracerebral haemorrhage and cardiovascular diseases in the later stages of life. The combination of clinical and risk variables and a panel of multiple biomarkers will help clinicians in risk stratification and prognostication of clinical outcomes among preeclamptic women. We evaluated MMP-9 (matrix metalloproteinase - 9) and ST2 (suppression of tumorigenicity 2) for utility as biomarkers and for predicting maternal and foetal outcomes in women with preeclampsia. MethodsThis prospective cohort study involved 49 preeclamptic women and 80 healthy controls. Biomarkers were measured in plasma using ELISA. The patients were followed up to assess maternal and foetal outcomes. ResultsThe mean value of MMP-9 was 2.42 ng/mL in the preeclamptic group and 2.67 ng/mL in controls. The mean value of ST2 (1937.4 ± 747.81) in the preeclamptic group was high compared to the control group (1005.7 ± 683.6) and the difference was significant (P = 0.0001). The study population was divided into those with high and low MMP-9 and those with high and low ST2. Lower levels of MMP-9 seemed to be related to both early and late onset preeclampsia. The ROC (Receiver Operating Characteristic) curve did not show the ability to predict maternal and foetal outcomes. DiscussionOur study demonstrated that women with preeclampsia had low MMP-9 and high ST2 compared to healthy pregnant women. But neither of the biomarkers could predict complications of preeclampsia.

Lymphocyte immunophenotyping and concentration of MMP-9 in transudates and exudates in horses

This study is the first to provide information on the lymphocyte subpopulations in peritoneal effusions in horses. Peritoneal transudates (n = 12), peritoneal exudates (n = 6) and a pleural exudate (n = 1) were analyzed. The total nucleated cell count (TNCC), total protein (TP) and matrix metalloproteinase-9 (MMP-9) concentration determined by ELISA were measured and routine cytological evaluation was performed. CD3, CD4, CD8 and CD21 positive cells were detected by flow cytometry. A higher percentage of neutrophils (P < 0.05) and higher MMP-9 (P < 0.01) levels were found in exudates. A higher percentage of macrophages (P < 0.05) and lymphocytes (P < 0.01) were found in transudates. CD4 + lymphocytes were the most common lymphocyte subpopulation in all samples. CD21 + lymphocytes were the least common in all samples. A large variability in the percentage of CD21 + lymphocytes was found in exudates. The percentage of CD21 + lymphocytes positively correlated with the level of total protein (r = 0.5704, P < 0.05). The correlation was even stronger in the group of exudates. The percentages of lymphocyte subpopulations did not correlate with the level of MMP-9 or with cytological findings. The level of MMP-9 positively correlated with the percentage of neutrophils (r = 0.4980, P < 0.05), the level of TP (r = 0.7855, P < 0.01) and TNCC (r = 0.6129, P < 0.01). A significantly higher level of MMP-9 was detected in euthanized horses than in horses that survived (P < 0.05). However, it was shown that the level of MMP-9 in the peritoneal fluid can change significantly in a short time. More studies on repeated abdominocentesis could contribute to elucidating the role of MMP-9 as a prognostic indicator.

Comparative Study of the Pain, Function, and Biomarkers of Joint Disease in the Transition to Adulthood in Individuals With and Without Cerebral Palsy.

Biomarkers have potential to identify early signs of joint disease. This study compared joint pain and function in adolescents and young adults with cerebral palsy compared with individuals without. This cross-sectional study compared individuals with cerebral palsy ( n = 20), aged 13-30 yrs with Gross Motor Function Classification System I-III and age-matched individuals without cerebral palsy ( n = 20). Knee and hip joint pain measured using Numeric Pain Rating Scale and Knee injury and Osteoarthritis Outcome Score and Hip dysfunction and Osteoarthritis Outcome Score surveys. Objective strength and function were also measured. Biomarkers for tissue turnover (serum cartilage oligomeric matrix protein, urinary C-terminal crosslinked telopeptide of type II collagen) and cartilage degradation (serum matrix metalloproteinase 1, matrix metalloproteinase 3) were measured in blood and urinary samples. Individuals with cerebral palsy had increased knee and hip joint pain, reduced leg strength, reduced walking and standing speeds, and ability to carry out activities of daily living ( P < 0.005) compared with controls. They also had higher serum matrix metalloproteinase 1 ( P < 0.001) and urinary C-terminal crosslinked telopeptide of type II collagen levels ( P < 0.05). Individuals with cerebral palsy who were Gross Motor Function Classification System I and II demonstrated reduced hip joint pain ( P = 0.02) and higher matrix metalloproteinase 1 levels ( P = 0.02) compared with Gross Motor Function Classification System III. Individuals with cerebral palsy with less severe mobility deficits had higher matrix metalloproteinase 1 levels likely due to more prolonged exposure to abnormal joint loading forces but experienced less joint pain.

Current Smoking Determines the Levels of Circulating MPO and MMP-9 in Adults with Coronary Artery Disease and Obstructive Sleep Apnea.

(1) Background: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which a rupture of atherosclerotic plaques and oxidative stress play a role in the initiation and progression of the disorder. Circulating levels of myeloperoxidase (MPO), as an oxidative stress marker, as well as matrix metalloproteinase-9 (MMP-9), as a destabilizer of plaques, are known to be elevated in patients with CAD and are associated with worse prognosis. Some studies have suggested that OSA is associated with MPO and MMP-9, but the effect of OSA on these biomarkers in cardiac cohorts is unknown. (2) Aims: We addressed the determinants of high MPO and MMP-9 in a CAD cohort with concomitant OSA. (3) Materials and Methods: The current study was a secondary analysis of the RICCADSA trial that was conducted in Sweden between 2005 and 2013. A total of 502 revascularized CAD patients with OSA (apnea-hypopnea index [AHI] ≥ 15 events/h; n = 391) or no-OSA (AHI < 5 events/h; n = 101), based on a home sleep apnea test, and who had blood samples at baseline were included in the analysis. The patients were dichotomized into a high or low MPO and MMP-9 groups, based on the median cut-off values. (4) Results: The mean age of the participants was 63.9 (±8.6), and 84% of the study cohort were men. Median values of MPO and MMP-9 levels were 116 ng/mL and 269 ng/mL, respectively. In different multivariate linear and logistic regression models, neither OSA nor OSA severity in terms of AHI and oxygenation indices were associated with the high MPO and MMP-9 levels. Current smoking was significantly associated with both high MPO (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06-2.84; p = 0.030) and high MMP-9 levels (OR 2.41, 95% CI 1.44-4.03; p < 0.001), respectively. Other significant determinants were revealed as beta blocker use (OR 1.81, 95% CI 1.04-3.16; p = 0.036) for high MPO as well as male sex (OR 2.07, 95% CI 1.23-3.50; p = 0.006) and calcium antagonist use (OR 1.91, 95% CI 1.18-3.09; p = 0.008) for high MMP-9 levels. (5) Conclusions: Current smoking, but not OSA, was significantly associated with high MPO and MMP-9 levels in this revascularized CAD cohort. Smoking status should be seriously taken into consideration while evaluating the effects of OSA and its treatment on long-term adverse cardiovascular outcomes in adults with CAD.

Comparison of MMP-9 Density Between Triple Negative and HER2 Enriched Breast Carcinoma Subtypes

Background&#x0D; Matrix metalloproteinase-9 (MMP-9) is a protease that plays an important role in various biological processes of breast cancer. This marker may be useful in determining the prognosis and become a promising therapy, especially in breast carcinoma with an aggressive subtype including HER2 enriched and triple negative. Both subtypes have high MMP-9 expression, but it is necessary to differentiate them because they have different biological and molecular aspects. This study aims to compare the density of MMP-9 between triple negative and HER2 enriched breast carcinoma subtypes and their relationship with clinicopathological characteristics.&#x0D; &#x0D; Methods&#x0D; This is a cross sectional study using 32 samples of paraffin blocks and slides of breast carcinoma patients with triple negative and HER2 Enriched subtypes at the Department of Anatomical Pathology Faculty of Medicine Sriwijaya University/Dr. Mohammad Hoesin Hospital Palembang for the period January 1, 2016 to December 31, 2019. Each sample was stained with MMP-9 antibodies immunohistochemistry (polyclonal, Abcam). Comparative analysis of MMP-9 density between the two subtypes was carried out using the median value based on the Mann-Whitney analysis. MMP-9 density was categorized as high and low based on the ROC curve and analyzed by using chi-square test to assess its association with clinicopathological characteristics.&#x0D; &#x0D; Results&#x0D; Mann-Whitney test showed that the MMP-9 density was higher in the HER2 enriched subtype (median 12.0) than triple negative (median 8.8) with a p value of 0.632. The relationship distribution of high MMP-9 density was found in the category of age group &gt;40 years old (60.0%), positive lymphovascular invasion (86.7%) and histological grade III (80.0%) with p values of 0.798, 0.402 and 0.691.&#x0D; &#x0D; Conclusion&#x0D; MMP-9 density in HER2 enriched subtype was higher than triple negative subtype, but statistically not significant.

Complete breakdown of copper-free clickable doxorubicin nanoclusters for real-time tumor proliferation tracking

Size-dependent localization of nanoscale carriers is essential for enhancing therapeutic windows and minimizing side effects in anticancer therapy. Therefore, we prepared polymeric nanoparticle (NP) clusters that could be clicked in response to the surrounding enzyme levels in tumor tissues to accomplish diagnostic and therapeutic systems with a single nanocluster. Multiarmed poly(ethylene glycol) (PEG) was conjugated with multiple molecules of doxorubicin (DOX), and the longest arm was designed to be abolished in response to matrix metalloproteinase (MMP) levels. These PEG conjugates self-assembled into anticancer NPs, and PEG shells were peeled at high threshold MMP levels. These DOX NPs were copper-free clicked with azide-functionalized quantum dots in response to the surrounding MMP levels. Therefore, the fluorescence of the systems was quenched, which was dependent on the tumor cell types. Ex vivo experiments on harvested tumor tissues validated the correlation between fluorescence quenching and tumor weight, highlighting the potential of these NPs as tools for monitoring tumor progression and therapeutic efficacy.

Matrix Metalloproteinase-7 Associated with Congestive Heart Failure in Peritoneal Dialysis Patients: A Prospective Cohort Study.

Matrix metalloproteinase-7 (MMP7) is markedly expressed in patients with chronic kidney disease; its expression in dialysate and role in patients undergoing peritoneal dialysis (PD) have not been well established. Participants undergoing PD from June 1st, 2015, to June 30th, 2020, were involved and were followed up every 3 months for the first year and every 6 months thereafter until death, PD withdrawal, or the end of the study. Data at each follow-up point were collected and analyzed for the association with congestive heart failure (CHF), PD withdrawal, and combined endpoint. A total of 283 participants were included in this study. During a median follow-up of 21 months, 20 (7%) participants died, 93 (33%) withdrew from PD, and 105 (37%) developed CHF. A significantly increased level of serum and dialysate MMP7 was observed at baseline. Dialysate MMP7 presented a good linearity with serum MMP7. Baseline serum and dialysate MMP7 levels were associated with CHF in multivariable Cox proportional hazards regression models. After categorization, participants with high baseline MMP7 levels had a higher incidence of CHF (42%), and the hazard ratios (95% confidence intervals) were 1.595 (1.023-2.488). Interestingly, participants with higher serum MMP7 levels were trended to use dialysate with higher glucose concentration. However, the ultrafiltration volumes were not significantly increased. Higher MMP7 levels were also positively associated with PD withdrawal and combined endpoint. The expression of MMP7 in serum and dialysate was markedly increased and was tightly associated with the risk of CHF in PD patients. This finding suggests that the measurement of MMP7 may inform strategies for managing CHF at an earlier stage.

Genomic analysis of matrix metalloproteinases affecting the prognosis and immunogenic profile of gastric cancer.

This study systematically and comprehensively analyzed the characteristics of matrix metalloproteinases (MMPs) in gastric cancer (GC) and revealed the relationship between MMPs and prognoses, clinicopathological features, tumor microenvironment, gene mutations, and drug therapy response in patients with GC. Based on the mRNA expression profiles of 45 MMP-related genes in GC, we established a model that classified GC patients into three groups based on cluster analysis of the mRNA expression profiles. The 3 groups of GC patients showed significantly different prognoses as well as tumor microenvironmental characteristics. Next, we used Boruta's algorithm and PCA method to establish an MMP scoring system and found that lower MMP scores were associated with better prognoses, lower clinical stages, better immune cell infiltration, lower degrees of immune dysfunction and rejection, and more genetic mutations. Whereas a high MMP score was the opposite. These observations were further validated with data from other datasets, showing the robustness of our MMP scoring system. Overall, MMP could be involved in the tumor microenvironment (TME), clinical features, and prognosis of GC. An in-depth study of MMP patterns can better understand the indispensable role of MMP in the development of GC and reasonably assess the survival prognosis, clinicopathological features, and drug efficacy of different patients, thus providing clinicians with a broader vision of GC progression and treatment.

Metalloproteinase-9 in the ocular surface of patients with implanted Boston type 1 keratoprosthesis.

To characterize the presence of ocular surface inflammation, using matrix metalloproteinase 9 (MMP-9) as a marker, in the ocular surface of eyes with implanted Boston Keratoprosthesis type 1 (KPro). Patients with implanted KPro at a single tertiary center were recruited to assess ocular inflammation. MMP-9 was measured using InflammaDry® test in both eyes of each patient. The non-KPro eye served as control. Rate of positivity of MMP-9 was compared between groups. Possible associations between ocular surface inflammation and the development of postoperative complications were evaluated using univariate statistical analysis. Fifty eyes from 25 patients were included. The mean age was 50 years old. Non-inflammatory indications for KPro were predominant among patients. Eighty eight percent of KPro eyes had a positive test for MMP-9 while only 25% of control eyes were positive (p<001). The most common complications were retroprosthetic membrane, epithelial defects, and sterile corneal melt. The presence of a strong positive result was associated to a higher frequency of complications (80% of eyes) compared to a faint positive test (54%) and a negative test (33%). The KPro device appears to increase MMP-9 levels in the ocular surface. High MMP-9 levels may be associated with higher risk of complications. MMP-9 testing can be useful to assess subclinical ocular surface inflammation with a potential role in the postoperative care of KPro patients.

Evaluation of the Salivary Matrix Metalloproteinase-9 in Women With Polycystic Ovaries Syndrome and Gingival Inflammation: A Case-Control Study.

Background Polycystic ovary syndrome (PCOS) is an endocrine disease of women of reproductive age that impacts their oral and systemic well-being. This study aimed to compare the gingival inflammation indices and matrix metalloproteinase-9 (MMP-9) of non-obese women with PCOS. Materials and methods This is a case-control study in which 78 women were referred to the Babol Clinic Hospital in Northern Iran between 2018 and 2019. They were divided into three groups:26 women with PCOS and gingivitis, 26 women with PCOS with no gingivitis, and 26 women with no PCOS and no gingivitis as a control group. After recording the anthropometric and demographic variables, fasting saliva samples were taken from all participants before any periodontal intervention. These samples were transferred to Babol Molecular Cell Research Center under highly guaranteed cold-chain conditions to measure the serum levels of MMP-9. Periodontal status was evaluated for Gingival Index (GI), Plaque Index (PI), and Bleeding on Probing (BOP). Analysis of variance was used to compare the mean results for these indices. The significance level was considered when p ≤ 0.05. Results All the gingival indices were significantly higher for women with PCOS with gingivitis compared to the results for women from the other two groups. Similarly, women with PCOS showed high salivary MMP-9 levels but were within the normal reference ranges. Conclusion The gingival indices (GI, PI, and BOP) and salivary MMP-9 are higher in women with PCOS, regardless of the gingival status.

Metformin Directly Binds to MMP-9 to Improve Plaque Stability

Vulnerable atherosclerotic plaque rupture is the principal mechanism that accounts for myocardial infarction and stroke. High matrix metalloproteinase-9 (MMP-9) expression and activity have been proven to lead to plaque instability. Metformin, a first-line treatment for type 2 diabetes, is beneficial to plaque vulnerability. However, the mechanism underlying its anti-atherogenic effect remains unclear. Molecular docking and surface plasmon resonance experiments showed that metformin directly interacts with MMP-9, and incubated MMP-9 overexpressing HEK293A cells with metformin (1 μmol·L-1) significantly attenuates MMP-9's activity using zymography and MMP activity assays. Moreover, metformin treatment drives MMP-9 degradation. Next, we constructed a carotid artery atherosclerotic plaque model and administered consecutive 14-day metformin (200 mg·kg-1·d-1) treatment by intragastric gavage. Immunofluorescence staining of the right carotid common artery and serum MMP activity assay results showed that metformin treatment decreased local plaque MMP-9 protein level and circulating MMP-9 activity, respectively. Histochemical staining revealed that after metformin treatment, the collagen content in plaque was significantly preserved, and the plaque vulnerability index decreased. These findings suggested that metformin improved atherosclerotic plaque stability by directly binding to MMP-9 and driving its degradation.

Relationship between serum TGF- β 1, MMP-9 and IL-1β and pathological features and prognosis in breast cancer.

To investigate the levels of serum transforming growth factor-β 1 (TGF-β1), Matrix metalloproteinase-9 (MMP-9) and Interleukin-1 β (IL-1 β) in breast cancer (BC), and analyzing their relationship with pathological features and prognosis. Retrospective analysis of 86 subjects with BC (BC subgroup) and another 50 healthy subjects (control subgroup) during the same period were included. The clinical data were collected. In this research, in BC subgroup, The levels of serum TGF- β 1, MMP-9 and IL-1 β were significantly higher than those in control subgroup. The levels of TGF- β 1 and MMP-9 in serum of BC subjects was correlated with clinical stage, histological grade, lymph node metastasis and molecular classification, but not with age, tumor size and menopausal status. The level of serum IL-1 β was related to tumor size, clinical stage, histological grade and lymph node metastasis. Multivariate Logistic regression analysis showed that the high level of serum TGF- β1 and MMP-9 was independent risk factors for BC. High level of serum IL-1 β was not an independent risk factor for BC. The 3-year disease-free survival rate in high TGF- β1 subgroup and high MMP-9 subgroup was significantly lower than that in low TGF- β 1 subgroup and low MMP- 9 subgroup. To conclude, serum TGF- β 1, MMP-9 and IL-1β are highly expressed in BC, and the subjects with elevated serum levels of TGF- β 1 and MMP-9 suggests poor prognosis.

High Serum Level of Matrix Metalloproteinase-1 (MMP-1) Correlates Positively with The Severity of Photoaging Facial Wrinkles

Background: Matrix metalloproteinase-1 was chosen in this study because it is a subgroup of MMPs that play an essential role in the photoaging process of collagenases with degradation of collagen types 1 and 2 as a result of direct UVA and UVB exposure with significantly increased regulation of these exposures compared to other types of MMPs. The purpose of this study is to prove a positive correlation between high MMP-1 serum levels and the severity of facial wrinkles in photoaging subjects. Methods: Observational analytic study using a cross-sectional approach with comparative analysis aims to determine differences in the severity of facial wrinkles in patients experiencing Photoaging based on MMP-1 levels. Subjective clinical observation of wrinkles with Glogau score and objective use of the A-One-Facial Analyzer tool. Analyzing using SPSS 26. Results: 51 subjects were divided into two groups, 30 photoaging, and 21 non-photoaging. The results of the A-One-Facial Analyzer Photoaging group were 5.30 (4.70-6.50) and without Photoaging were 4.80 (4-5). MMP-1 serum levels in the Photoaging group median of 17.69 (9.78-84.07) pg./ml and non-photoaging group 11.56 (8.07-19.62) pg/ml (p &lt;0.001). Spearman Rho test between MMP-1 levels and wrinkles on the face obtained a moderate positive relationship with a correlation coefficient value (r) of 0, 5 and p-value &lt;0.001. The result of the coefficient β was 41,5%, R-square 48%, and it was statistically significant with p = 0.002. Conclusion: High serum levels of matrix metalloproteinase -1 (MMP-1) have a positive correlation with the severity of facial skin wrinkles that experience Photoaging.