Matrix Metalloproteinase-9 Levels Research Articles

Maternal dietary deficiency in choline reduced levels of MMP-2 levels in blood and brain tissue of male offspring mice.

Ischemic stroke is one of the leading causes of disability and death globally, with a rising incidence in younger age groups. It's well known that maternal diet during pregnancy and lactation is vital for the early neurodevelopment of offspring. One-carbon (1C) metabolism, including folic acid and choline, plays a vital role in closure of the neural tube in utero. However, the impact of maternal dietary deficiencies in 1C on offspring neurological function following ischemic stroke later in life remains undefined. The aim of this study was to investigate inflammation in blood and brain tissue of offspring from mothers deficient in dietary folic acid or choline. Female mice were maintained on either a control or deficient diets prior to and during pregnancy and lactation. When offspring were 3-months of age, ischemic stroke was induced. One and half months later blood and brain tissue were collected. We measured levels of matrix-metalloproteases (MMP)-2 and 9 in both plasma and brain tissue, and report reduced levels of MMP-2 in both, with no changes observed in MMP-9. This observation supports our working hypothesis that maternal dietary deficiencies in folic acid or choline during early neurodevelopment impact the levels of inflammation in offspring after ischemic stroke.

NR2F1 overexpression alleviates trophoblast cell dysfunction by inhibiting GDF15/MAPK axis in preeclampsia.

Abnormal functions of trophoblast cells are associated with the pathogenesis of preeclampsia (PE). Nuclear receptor subfamily 2 group F member 1 (NR2F1) acts as a transcriptionally regulator in many diseases, but its role in PE remains unknown. Hypoxia/reoxygenation (H/R)-stimulated HTR-8/SVneo cells were used to mimic PE injury in vitro. NR2F1 overexpression alleviated trophoblast apoptosis, as evidenced by the decreased number of TUNEL-positive cells and the downregulation of caspase 3 and caspase 9 expression in cells. NR2F1 overexpression increased the invasion and migration ability of HTR-8/SVneo cells, accompanied by increased protein levels of matrix metalloproteinase (MMP)-2 and MMP-9. mRNA-seq was applied to explore the underlying mechanism of NR2F1, identifying growth differentiation factor 15 (GDF15) as the possible downstream effector. Dual-luciferase reporter, ChIP-qPCR, and DNA pull-down assays confirmed that NR2F1 bound to the promoter of GDF15 and transcriptionally inhibited its expression. GDF15 overexpression increased apoptosis and decreased the ability of invasion and migration in HTR-8/SVneo cells expressing NR2F1. MAPK pathway was involved in the regulation of PE. Administration of p38 inhibitor, ERK inhibitor, and JNK inhibitor reversed the effect of simultaneous overexpression NR2F1 and GDF15 on trophoblast apoptosis, invasion, and migration. Our findings demonstrated that NR2F1 overexpression inhibited trophoblast apoptosis and promoted trophoblast invasion and migration. NR2F1 might negatively regulate GDF15 expression by binding to its promoter region, which further inhibited MAPK signaling pathway in PE. Our study highlights that NR2F1 might sever as a potential target in PE.

Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinases explored in relation to the severity and progression of diabetic retinopathy in patients with type 1 diabetes: baseline and prospective analyses

AimsTo explore whether circulating matrix metalloproteinase-2 (MMP-2), MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin, MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1), MMP-14, TIMP-2 and TIMP-3 were associated with the severity and progression of diabetic retinopathy...

Evaluation of selected biomarkers in the diagnosis of asthma in children

Introduction and objective: Asthma is one of the most common chronic diseases in the paediatric population. The aim of this study was to evaluate selected biomarkers: fractional exhaled nitric oxide (FeNO), eosinophil count, periostin; and potential biomarkers: progranulin, matrix metalloproteinase-9 (MMP-9) and tumour necrosis factor alpha (TNFα) in the diagnosis of asthma in children. Materials and methods: The study group consisted of 25 children with atopic asthma in a stable period of the disease, aged 6–17 years. The control group consisted of 21 healthy children aged 6–18 years with no history of allergic diseases. Results: Significantly higher serum periostin levels were observed in children with asthma compared to the control group. There were no statistically significant differences in progranulin, periostin and MMP-9 levels between asthmatic children vs. healthy controls, or between patients with controlled vs. uncontrolled asthma. Children with uncontrolled asthma had significantly higher FeNO levels compared to children with controlled asthma. Exhaled FeNO levels were significantly higher in children with eosinophil levels above 0.3 × 103/µL than in those with eosinophil levels below 0.3 × 103/µL. Children with elevated FeNO had higher progranulin levels compared to children with normal FeNO values. There was a statistically significant positive correlation between FeNO and serum progranulin levels. Conclusions: Periostin may be used as a biomarker of atopic asthma in children. The applicability of FeNO and eosinophil count in the diagnosis of asthma in children has been confirmed. The role of progranulin and MMP-9 in the pathogenesis of asthma and their usefulness as a biomarker in children requires further study.

Phytocosmetic potential of Blumea balsamifera oil in mitigating UV-induced photoaging: Evidence from cellular and mouse models

Ethnopharmacological relevanceBlumea balsamifera (L.) DC. (BB), the source of Blumea balsamifera oil (BBO), is an aromatic medicinal plant, renowned for its pharmacological properties and its traditional use in Southeast Asian countries such as China, Thailand, Vietnam, Malaysia, and the Philippines for centuries. Traditionally, BB has been used as a raw herbal medicine for treating various skin conditions like eczema, dermatitis, athlete's foot, and wound healing for skin injuries. Aim of the studyThis research aimed to explore the inhibitory effects of BBO on skin aging using two models: in vitro analysis with human dermal fibroblasts (HDF) under UVB-induced stress, and in vivo studies on UVA-induced dorsal skin aging in mice. The study sought to uncover the mechanisms behind BBO's anti-aging effects, specifically, its impact on cellular and tissue responses to UV-induced skin aging. Materials and methodsWe applied doses of 10–20 μL/mL of BBO to HDF cells that had been exposed to UVB radiation to simulate skin aging. We measured cell viability, and levels of reactive oxygen species (ROS), SA-β-gal, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In addition, we investigated the involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways in mediating the anti-aging effects of BBO. Histopathological and biochemical analyses were conducted in a mouse model to examine the effects of BBO on UV-induced photoaging. ResultsUV exposure accelerated aging, and caused cellular damage and inflammatory responses through ROS-mediated pathways. In HDF cells, BBO treatment countered the UVB-induced senescence, and the recovery of cell viability was correlated to notable reductions in SA-β-gal, ROS, pro-inflammatory cytokines, and MMPs. Mechanistically, the anti-aging effect of BBO was associated with the downregulation of the JNK/NF-κB signaling pathways. In the in vivo mouse model, BBO exhibited protective capabilities against UV-induced photoaging, which were manifested by the enhanced antioxidant enzyme activities and tissue remodeling. ConclusionsBBO effectively protects fibroblasts from UV-induced photoaging through the JNK/NF-κB pathway. Recovery from photoaging involves an increase in dermal fibroblasts, alleviation of inflammation, accelerated synthesis of antioxidant enzymes, and slowed degradation of ECM proteins. Overall, BBO enhances the skin's defensive capabilities against oxidative stress, underscoring its potential as a therapeutic agent for oxidative stress-related skin aging.

Investigating the Antifibrotic Effects of β-Citronellol on a TGF-β1-Stimulated LX-2 Hepatic Stellate Cell Model.

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, β-citronellol (β-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-β1 to induce fibrogenesis were co-treated with crude KL extract and β-CIT. Gene expression was analyzed by real-time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The release of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein-ligand interactions. The results showed that both crude KL extract and β-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of β-CIT. This study demonstrates the ability of KL extract and β-CIT to inhibit HSC activation during TGF-β1-induced fibrogenesis, suggesting a promising role of β-CIT in anti-hepatic fibrosis therapies.

Prognostic impact of cytokines and chemokines in bronchoalveolar lavage fluid on acute exacerbation of fibrosing interstitial lung disease

Background and objectiveAcute exacerbation of fibrosing interstitial lung disease (AE-FILD) is a serious condition with a high mortality rate. We aimed to comprehensively analyze cytokines in bronchoalveolar lavage fluid and their association with the clinical course of AE-FILD. MethodsWe retrospectively enrolled 60 patients with AE-FILD who underwent bronchoalveolar lavage. We comprehensively measured 44 cytokines and chemokines in the obtained bronchoalveolar lavage fluid using a Luminex analyzer. Patients were grouped into those who died within 90 days (non-survival group) and survived beyond 90 days (survival group) to investigate the association of the levels of cytokines and chemokines with mortality. ResultsThe levels of matrix metalloproteinase 1 (p = 0.003), granulocyte-macrophage colony-stimulating factor (p = 0.040), interleukin 6 (p = 0.047), interleukin 8 (p = 0.050), monocyte chemoattractant protein-1 (p = 0.043), and eotaxin (p = 0.044) were significantly higher in the non-survival group than in the survival group. In the receiver operating characteristic analysis, their areas under the curve were 0.80, 0.68, 0.71, 0.70, 0.70, and 0.72, respectively. Using machine learning with these six cytokines and chemokines, the predictive accuracy for the survival group was 0.94. ConclusionsOur study demonstrated that several cytokines and chemokines in bronchoalveolar lavage fluid could be prognostic predictors in patients with AE-FILD.

The Role of Melatonin and Matrix Metalloproteinases in Breast Cancer Pathogenesis: A Comprehensive Review

Background: Breast cancer is a heterogeneous disease with molecular subtypes including Triple Negative Breast Cancer (TNBC), HER2/neu-positive, Luminal Type A, and Luminal Type B, each with unique clinical behaviors and therapeutic responses. This study investigates the role of melatonin, matrix metalloproteinases (MMPs), pro-inflammatory cytokines (IL6 and TNF-alpha), and lactate dehydrogenase (LDH) isoenzymes in breast cancer pathogenesis. Methods: Over three years, 171 breast cancer patients were studied. Blood and urine samples were collected to measure melatonin, MMPs, IL-6, TNF-alpha, LDH-1, and LDH-5 levels. Circulating tumor cells (CTCs) were isolated using density gradient centrifugation and immunomagnetic separation. Melatonin receptor expression on CTCs was analyzed by flow cytometry and immunocytochemistry. Plasma concentrations of melatonin were measured using high-performance liquid chromatography (HPLC), and MMPs, IL-6, TNF-alpha, LDH isoenzymes were quantified using enzyme-linked immunosorbent assays (ELISAs) and electrophoretic methods. Results: The expression of melatonin receptors was lowest in TNBC patients, higher in HER2/neu-positive and ER/PRnegative patients, and highest in Luminal Type A and B patients. TNBC patients exhibited elevated LDH-1 and inflammatory cytokines (IL-6, TNF-alpha), with significantly decreased melatonin levels. HER2/neu-positive patients showed elevated LDH5 and moderate decreases in melatonin. Luminal Type B and A patients had varying degrees of biomarker elevation and melatonin receptor expression. Discussion: The findings suggest a correlation between reduced melatonin signaling and aggressive breast cancer phenotypes, particularly TNBC. Elevated MMPs and pro-inflammatory cytokines underscore the role of inflammation and ECM degradation in cancer progression. Melatonin’s potential inhibitory effects on these pathways highlight its therapeutic promise. The combined assessment of melatonin, MMPs, cytokines, and LDH could guide personalized treatment strategies. Conclusion: This study underscores melatonin’s multifaceted role in breast cancer pathogenesis. Melatonin receptor expression, along with MMP, IL-6, TNF-alpha, and LDH levels, provides a detailed molecular landscape of breast cancer subtypes. Integrating melatonin supplementation into therapeutic regimens holds promise for improving outcomes, particularly inaggressive subtypes like TNBC. Further research and clinical trials are essential to validate these findings and develop effective melatonin-based therapies.

OxLDL as a prognostic biomarker of plaque instability in patients qualified for carotid endarterectomy.

Atherosclerotic plaque instability increases the risk of stroke. As such, determining the nature of an instability atherosclerotic plaque may speed up qualification for carotid endarterectomy (CEA), thus reducing the risk of acute vascular events. The aim of the study was to determine the diagnostic value of oxidized LDL cholesterol (ox-LDL), matrix metalloproteinase 9 (MMP-9) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum as a prognostic markers of instability atherosclerotic plaques. Serum was collected from 67 patients who underwent CEA in accordance with the qualification criteria. The levels of ox-LDL, MMP-9 and 8-OHdG were assessed by ELISA. The predictive value of the markers was determined based on an ROC curve, and the cut-off points with the highest sensitivity and specificity were determined. Patients with unstable atherosclerotic plaque had significantly higher serum ox-LDL, MMP-9 and 8-OHdG values. It was found that in patients before CEA, ox-LDL >31.4 ng/mL was associated with an 82.5% probability of unstable atherosclerotic plaque, MMP-9 >113.1 ng/mL with 78.6%, and 8-OHdG >2.15 ng/mL with 64.7%. Multivariate regression analysis found ox-LDL to be an independent factor associated with plaque instability. Patients with unstable plaques tend to have higher serum levels of ox-LDL, MMP-9 and 8-OHdG compared to those with stable plaques. The optimal cut-off point for ox-LDL (AUC 0.86, p <0.0001) was 31.14 ng/mL, with 91.18% sensitivity and 78.79% specificity. The high sensitivity and specificity of ox-LDL suggests that it can be used as an independent marker of plaque instability.

Local proteolytic system indicators as suspective factors of keratolysis development after urgent keratoplasty

Purpose: to determine the concentration of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the tear of patients with cornea melting and to assess whether these factors can be used as prognostically significant biomarkers of keratolysis. Material and methods. 20 patients who underwent urgent penetrating keratoplasty were tested for cornea perforation (melting) before and after the procedure. For control, 12 healthy adults (24 eyes) were tested. The tear fluid was collected before the surgery and on the 7th day after it with the help of filtering paper. MMP-9 and TIMP-1 concentrations were determined by ELISA. The course of the early postoperative period was assessed according to the area of keratotransplant epithelization on the 7th day after surgery. Results. MMP-9 and TIMP-1 concentrations in the tears of all patients before the surgery were significantly higher than the ones of healthy controls. The patients who were supposed to have re-keratoplasty had a significantly higher MMP-9 concentration than the ones who expected the first keratoplasty. An uncomplicated early postoperative period showed a statistically significant decrease of MMP-9 and TIMP-1 concentrations, whilst the complicated one demonstrated a significant increase of both markers. The highest increase of both markers was shown by the patients who underwent re-keratoplasty. Conclusion. MMP-9 concentration in the tears is a valid marker of the clinical course of the early post-keratoplasty period. To ensure a successful donor cornea engraftment, the levels of MMP-9 and TIMP-1 in the tear must be high enough before the surgery and the concentration of the ferment should decrease timely after its main functions have been completed. A 2-fold (or greater) decrease of MMP-9 concentration in the tear on the 7th day after keratoplasty can be considered a marker of the favorable prognosis for engraftment.

Exploring the effect of wound related pain on psychological stress, inflammatory response, and wound healing.

The relationship between pain and poor healing is intricate, potentially mediated by psychological stress and aberrations in inflammatory response. The purpose of this study was to examine the biopsychosocial model of pain by assessing the relationships between pain, stress, inflammation and healing in people with chronic wounds. This was a 4-week prospective observational study to explore the relationship of pain, stress, inflammation and wound healing in a convenience sample of patients with chronic wounds in a chronic care hospital in Canada. Only subjects over 18 with chronic wounds were recruited into the study. Chronic wounds were defined by the duration of wounds for more than 4 weeks of various aetiologies including wounds caused by pressure injuries, venous disease, arterial insufficiency, surgery or trauma and diabetic neuropathy. Participants were evaluated for pain by responding to the Brief Pain Inventory-Short Form, the McGill Pain Questionnaire-Short Form and the Leeds Assessment of Neuropathic Symptoms and Signs scale. Stress was measured by the Perceived Stress Scale (PSS). All wounds were assessed with the Pressure Ulcer Scale for Healing tool. The levels of matrix metalloproteinases were analysis by obtaining wound fluid from all participants. A total of 32 individuals with chronic wounds participated in the study. Correlation analysis indicated pain severity was positively and significantly related to pain interference, McGill Pain Questionnaire scores, neuropathic pain and matrix metalloproteinase levels. Logistic regression was used to determine the predictors for high or low perceived stress. The only significant variable that contributed to the stress levels was BPI-I. Results suggested that participants who experienced higher levels of pain interference also had an increased odds to report high level of stress by 1.6 times controlling for all other factor in the model. Pain is a complex biopsychosocial phenomenon affecting quality of life in people with chronic wounds. Results of this study identified a significant relationship between pain, stress and wound healing.

Impact of Hyperhomocysteinemia on Cytokine and Matrix Metalloproteinases Contents in Rat Skeletal Muscle

Abstract Background: High levels of homocysteine (Hcy) in the blood (hyperhomocysteinemia [HHcy]) are associated with many pathologies, including atherosclerosis, coronary heart disease, stroke, neurological disorders, and a decrease in muscle mass and strength. The present study aimed to evaluate the levels of pro- and anti-inflammatory cytokines and matrix metalloproteinases (MMPs) in skeletal muscle of rats with experimental HHcy. Methods: HHcy in rats of two age groups was induced by intragastric administration of D, L-thiolactone Hcy for 8 weeks. The criterion for the development of pathological conditions was a blood Hcy level above 15 mmol L−1. Cytokine and MMP levels in muscle homogenate were determined by enzyme-linked immunosorbent assay. Results: The findings of the study on the content of pro-inflammatory cytokines in skeletal muscles of rats with hyperhomocysteinemia indicated the following. For immature rats, the greatest reduction in tumor necrosis factor-α and interleukin-8 (IL-8) content was observed, whereas, for mature individuals, the most pronounced decline in IL-1b was evident in skeletal muscle tissue under the pathology state. The content of anti-inflammatory interferon-γ was also reduced in the muscles of both age groups by 30% compared to the control, besides a decrease in the content of collagenase MMP-1 was also observed. Conclusions: The presence of HHcy is associated with metabolic changes in skeletal muscles, which can result in a depletion of cytokines and a slowing down of proteolytic remodeling. This, in turn, can lead to the development of muscular abnormalities, including dysfunction, weakness, and muscle degeneration.

Polymorphism of angiogenesis regulation factor genes (VEGF/VEGFR), and extracellular matrix remodeling genes (MMP/TIMP), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema.

Cells of various organs and systems perform their functions and intercellular interactions not in an inert environment, but in the microenvironment of tissue fluids. Violations of the normal drainage of tissue fluids accompany lymphedema. An important mechanism of angiogenesis and vasculogenesis regulation in tissue fluids is the production and reception of vascular endothelial growth factors in combination with the regulation of matrix metalloproteinases. The aim of the work was to perform: a comparative analysis of some polymorphisms of vascular endothelial growth factor and their receptors and the genes encoding matrix metalloproteinases in two forms of lymphedema; an analysis of the relationship of these genes' polymorphisms with the levels of vascular endothelial growth factor and matrix metalloproteinases and their inhibitors in serum and affected tissues. Polymorphism of VEGF (rs699947, rs3025039), KDR (rs10020464, rs11133360), NRP2 (rs849530, rs849563, rs16837641), matrix metalloproteinases MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242), Timp1 (rs6609533) and their combinations were analyzed by the Restriction Fragment Length Polymorphism method and TaqMan RT-PCR. The serum and tissue fluid levels were determined using the ELISA test system. Changes in the frequency distribution of MMP2 genotypes in primary and MMP3 in secondary lymphedema are shown. Significant frequency differences in NRP2 genotypes were revealed by comparing primary and secondary lymphedema. Features of the distribution of complex genotypes in primary and secondary lymphedema were revealed. The correlation analysis revealed the interdependence of the concentrations of the MMP, TIMP and VEGF products and differences in the structure of the correlation matrices of patients with both forms of lymphedema. It was shown that, in primary lymphedema, genotypes associated with low MMP2 and TIMP2 in serum and tissue fluid are detected, while in secondary lymphedema, other associations of the production levels with combined genetic traits are observed.

Mangiferin: A natural bioactive immunomodulating glucosylxanthone with potential against cancer and rheumatoid arthritis.

Mangiferin is a naturally occurring glucosylxanthone that has shown promising immunomodulatory effects. It is generally isolated from the leaves, peels, bark, and kernels of Mangifera indica Linn. Mangiferin is like a miraculous natural bioactive molecule that has an immunomodulatory function that makes it a potential therapeutic candidate for the treatment of rheumatoid arthritis (RA) and cancer. The anticancer activity of mangiferin acts by blocking NF-κB, as well as regulating the β-catenin, EMT, MMP9, MMP2, LDH, ROS, and NO, and also by the activation of macrophages. It has no cytotoxic effect on grown chondrocytes and lowers matrix metalloproteinase levels. Additionally, it has a potent proapoptotic impact on synoviocytes. The precise molecular mechanism of action of mangiferin on RA and malignancies is still unknown. This comprehensive review elaborates on the immunomodulatory effect of mangiferin and its anticancer and anti-RA activity. This also explained the total synthesis of mangiferin and its in vitro and in vivo screening models.

Exogenous autoinducer-2 alleviates intestinal damage in necrotizing enterocolitis via PAR2/MMP3 signaling pathway

BackgroundImbalanced intestinal microbiota and damage to the intestinal barrier contribute to the development of necrotizing enterocolitis (NEC). Autoinducer-2 (AI-2) plays a crucial role in repairing intestinal damage and reducing inflammation. ObjectiveThis study aimed to investigate the impact of AI-2 on the expression of intestinal zonula occludens-1 (ZO-1) and occludin proteins in NEC. We evaluated its effects in vivo using NEC mice and in vitro using lipopolysaccharide (LPS)-stimulated intestinal cells. MethodsPathological changes in the intestines of neonatal mice were assessed using histological staining and scoring. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay to determine the optimal conditions for LPS and AI-2 interventions. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the mRNA levels of matrix metalloproteinase-3 (MMP3), protease activated receptor-2 (PAR2), interleukin-1β (IL-1β), and IL-6. Protein levels of MMP3, PAR2, ZO-1, and occludin were evaluated using western blot, immunohistochemistry, or immunofluorescence. ResultsAI-2 alleviated NEC-induced intestinal damage (P < 0.05) and enhanced the proliferation of damaged IEC-6 cells (P < 0.05). AI-2 intervention reduced the mRNA and protein expressions of MMP3 and PAR2 in intestinal tissue and cells (P < 0.05). Additionally, it increased the protein levels of ZO-1 and occludin (P < 0.05), while reducing IL-1β and IL-6 mRNA expression (P < 0.05). ConclusionAI-2 intervention enhances the expression of tight junction proteins (ZO-1 and occludin), mitigates intestinal damage in NEC neonatal mice and IEC-6 cells, potentially by modulating PAR2 and MMP3 signaling. AI-2 holds promise as a protective intervention for NEC. AI-2 plays a crucial role in repairing intestinal damage and reducing inflammation.

Investigating the therapeutic effects of nimodipine on vasogenic cerebral edema and blood-brain barrier impairment in an ischemic stroke rat model

Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-min blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.

Adaptive enzyme-responsive self-assembling multivalent apelin ligands for targeted myocardial infarction therapy

Microvascular dysfunction following myocardial infarction exacerbates coronary flow obstruction and impairs the preservation of ventricular function. The apelinergic system, known for its pleiotropic effects on improving vascular function and repairing ischemic myocardium, has emerged as a promising therapeutic target for myocardial infarction. Despite its potential, the natural apelin peptide has an extremely short circulating half-life. Current apelin analogs have limited receptor binding efficacy and poor targeting, which restricts their clinical applications. In this study, we utilized an enzyme-responsive peptide self-assembly technique to develop an enzyme-responsive small molecule peptide that adapts to the expression levels of matrix metalloproteinases in myocardial infarction lesions. This peptide is engineered to respond to the high concentration of matrix metalloproteinases in the lesion area, allowing for precise and abundant presentation of the apelin motif. The changes in hydrophobicity allow the apelin motif to self-assemble into a supramolecular multivalent peptide ligand-SAMP. This self-assembly behavior not only prolongs the residence time of apelin in the myocardial infarction lesion but also enhances the receptor-ligand interaction through increased receptor binding affinity due to multivalency. Studies have demonstrated that SAMP significantly promotes angiogenesis after ischemia, reduces cardiomyocyte apoptosis, and improves cardiac function. This novel therapeutic strategy offers a new approach to restoring coronary microvascular function and improving damaged myocardium after myocardial infarction.

Peri-implant phenotype, calprotectin and MMP-8 levels in cases diagnosed with peri-implant disease

ObjectivesThe purpose of this prospective cohort study is to evaluate the effect of peri-implant phenotype (PPh) on the severity of peri-implant diseases and the results of non-surgical mechanical treatment (NSMT), along with calprotectin (CLP) and MMP-8(matrix metalloproteinase-8) levels.Materials and methods77 implants from 39 patients were included. The implants were categorized Group-1(peri-implant mucositis), Group-2(peri-implantitis).Baseline (0. Month-PrT) clinical parameters (PD, GI, PI, BOP, CAL) and radiographic bone loss were documented, and peri-implant crevicular fluid (PICF) samples were collected. Various intruments and methodologies were employed to assess PPh components (mucosa thickness, supracrestal tissue height, keratinized mucosa) and peri-implant attached mucosa (AM). NSMT was applied to diseased implant sites. All clinical parameters were reassessed again by taking PICF samples at the 6th month-after treatment (PT). In PICF samples obtained from both groups, MMP-8 and CLP levels were evaluated using the ELISA test.ResultsPrT-PD,PrT-GI,PrT-CAL and PrT-BOP percentage values in Group-2 were significantly higher than Group-1.PrT-PD,PrTPI scores are significantly higher in thin biotype implants. All components of the PPh and AM were significantly lower in thin biotype. Intra-group time-dependent changes of MMP-8 and CLP were significant in both groups (p < 0.05). When the relationship between thin and thick biotype and biochemical parameters was evaluated, the change in PrT-PT didn’t show a significant difference (p > 0.05).ConclusionsPPh plays a role in influencing the severity of peri-implant diseases. However, the impact of phenotype on NSMT outcomes was similar in both groups.Clinical relevanceThe PPh should be considered when planning implant surgery.

CHARACTERISTICS OF FOLLICULAR FLUID MORPHOLOGY AND LEVELS OF MATRIX METALLOPROTEINASE-1 AND ITS INHIBITOR-1 IN PATIENTS WITH POLYCYSTIC OVARIES IN ASSISTED REPRODUCTIVE TECHNOLOGY

Assisted reproductive technologies in patients with polycystic ovary syndrome (PCOS) is an effective way to realize reproductive function with a global pregnancy rate of 25–30 %. The purpose of the study is to establish the correlation between the levels of matrix metalloproteinase-1 (MMP-1) and its inhibitor-1 (TIMP-1) with follicular fluid morphology in PCOS patients undergoing assisted reproductive technology. Materials and Methods. The authors examined 26 PCOS patients aged 24–40. All patients were diagnosed with primary and secondary infertility lasting from 1 to 10 years. A comparative analysis of patients was carried out depending on the presence (n=12) or absence (n=14) of concomitant pathology, a history of endometrial hyperplasia. Clinical, anamnestic, instrumental and laboratory methods were used for analysis. Concentrations of MMP-1 and TIMP-1 in follicular fluid was determined by quantitative solid-phase ELISA. Follicular fluid morphology was studied according to wedge-shaped dehydration method. Statistica 10.0 wasnused for statistical data processing. Results. TIMP-1 level in PCOS patients was 2550±57.8 ng/ml, in PCOS patients with endometrial hyperplasia – 2694.4±87.8 ng/ml (p&lt;0.01). At the same time, the average MMP-1 level was low – 1.5±0.1 ng/ml. In PCOS patients, the 3rd (reactive) type of facies and markers indicating impaired blood supply were detected in the follicular fluid. In PCOS patients with endometrial hyperplasia, the 4th (chaotic) type of facies and markers indicating impaired elasticity, vascular sclerosis, and vasospasm was observed. It was found that the higher the TIMP-1 level, the more markers indicating destructive changes in the vessels of ovarian tissue (r=0.7) and the lower the chances of getting pregnant in assisted reproducrtive technology programs. Conclusions. In PCOS patients over 32 years of age, infertility duration of more than 4 years, having endometrial hyperplasia and surgical interventions in the past medical history (tubectomies for sactohydrosalpinx), TIMP-1 level significantly (p&lt;0.05) increases (≥2694 ng/ml) in the follicular fluid. Moreover, markers indicating destructive changes (vascular sclerosis, vasospasm and endothelial dysfunction) are identified. Thus, the chances of getting pregnant in assisted reproducrtive technology programs become lower.

Differences in metalloproteinases and their tissue inhibitors in the cerebrospinal fluid are associated with delirium

BackgroundThe aetiology of delirium is not known, but pre-existing cognitive impairment is a predisposing factor. Here we explore the associations between delirium and cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), proteins with important roles in both acute injury and chronic neurodegeneration.MethodsUsing a 13-plex Discovery Assay®, we quantified CSF levels of 9 MMPs and 4 TIMPs in 280 hip fracture patients (140 with delirium), 107 cognitively unimpaired individuals, and 111 patients with Alzheimer’s disease dementia. The two delirium-free control groups without acute trauma were included to unravel the effects of acute trauma (hip fracture), dementia, and delirium.ResultsHere we show that delirium is associated with higher levels of MMP-2, MMP-3, MMP-10, TIMP-1, and TIMP-2; a trend suggests lower levels of TIMP-4 are also associated with delirium. Most delirium patients had pre-existing dementia and low TIMP-4 is the only marker associated with delirium in adjusted analyses. MMP-2, MMP-12, and TIMP-1 levels are clearly higher in the hip fracture patients than in both control groups and several other MMP/TIMPs are impacted by acute trauma or dementia status.ConclusionsSeveral CSF MMP/TIMPs are significantly associated with delirium in hip fracture patients, but alterations in most of these MMP/TIMPs could likely be explained by acute trauma and/or pre-fracture dementia. Low levels of TIMP-4 appear to be directly associated with delirium, and the role of this marker in delirium pathophysiology should be further explored.