Matrix Metalloproteinase Research Articles

Curcumin Alleviates Airway Inflammation in Cough-Variant Asthmatic Rats by Modulating M1/M2 Macrophage Polarization.

With the increase of environmental pollution and atypical pathogen infections, the incidence of cough variant asthma (CVA) has been increasing annually, making it a pressing issue of the medical community. This study aims to observe the ameliorative effect of curcumin on a rat model of cough variant asthma. A rat model of cough variant asthma was induced by sensitization with ovalbumin combined with aluminum hydroxide (Al(OH)3), followed by repeated excitations. The drug was administered on the day of the initial nebulized attack, and gavage was administered for 14 d. Pathological changes in the lung tissues were observed, along with the assessment of cough susceptibility and airway resistance. The number of inflammatory cell eosinophils and leukocytes were determined in alveolar lavage fluid. Additionally, serum inflammatory factors and lung tissues Matrix Metalloproteinase-9 (MMP-9) protein were assessed. The level of M1/M2 macrophages was also detected. Following the administration of curcumin, there was reduced inflammatory infiltration, less disordered arrangement of the lung tissue, and decreased abnormal proliferation of lung tissues in cough variant asthma rats compared to the model group. Curcumin treatment led toa notable reduction in cough frequency, a significant decrease in pro-inflammatory factor concentration levels in serum and inflammatory cell counts in the alveolar lavage fluid, and a marked increase in anti-inflammatory factor levels (p < 0.05). Additionally, curcumin administration led to a significant increase in M2-type macrophage levels, while simultaneously decreasing the levels of M1-type macrophages (p < 0.05). The administration of curcumin effectively ameliorates ovalbumin-induced airway inflammation in cough-variant asthma rats. This effect is attributed to modulating macrophage polarization towards the anti-inflammatory M2 phenotype, thereby reducing airway inflammation, airway hyperresponsiveness, and lung tissue injury.

β-Cyclodextrin as an elicitor of polyphenolic contents of barley (Hurdeum vulgare) callus with antioxidant and anti-aging properties on human skin fibroblast cells (HFF2)

The skin, as the largest organ of body, plays a crucial role in human beauty, yet is vulnerable to aging due to ultraviolet radiation (UV) exposure. Various methods, including intradermal injection, surgery, laser therapy, stem cell applications, and cosmetic treatments, are employed to combat skin aging. Phytochemicals, known for their antioxidant properties, are extensively studied for skincare. Barley (Hurdeum vulgare) contains diverse phenolic compounds, exhibiting strong antioxidant activity, potentially reducing cellular aging. Here, we examined the anti-aging properties of barley callus extract enriched with polyphenols in human skin fibroblast cells (HFF2) exposed to UVB radiation. β-cyclodextrin was used as an elicitor at concentrations of 2.5 and 5 ppm to enhance the production of polyphenolic compounds in the callus of black and yellow barley. A concentration of 5 ppm significantly increased the phenolic and flavonoid content in both black and yellow barley callus. Analysis of the extracts obtained from the callus showed that aqueous and ethanolic extracts of black barley callus, at a concentration of 0.1 μg/mL, enhanced cell viability and decreased matrix metalloproteinase-1 (MMP-1) levels while increasing sirtuin (SIRT1) production in UVB-exposed HFF2 cells. These extracts also exhibited high antioxidant effects and promoted cell migration, DNA integrity, and cell cycle advancement. The findings suggest the potential use of black barley callus extract in cosmetics to mitigate UV radiation effects and premature skin aging. Additionally, β-cyclodextrin is highlighted as a valuable elicitor for enhancing polyphenol content, contributing to the antioxidant and anti-aging properties of black barley callus for skincare applications.

Prediabetes Associates with Matrix Metalloproteinase-8 Activation and Contributes to the Rapid Destruction of Periodontal Tissues.

The aim of this cross-sectional study was to investigate the relationship between periodontitis, potential periodontitis oral fluid biomarkers, and prediabetes. This study included 150 Greek adults aged 25 to 78 years who were tested with an Hemoglobin A1C (HBA1c) diagnostic system, an active-matrix metalloproteinase-8 (aMMP-8) point-of-care (PoC) test, and several salivary biomarkers enzyme-linked immunosorbent assay tests and gelatin zymography. A full-mouth clinical examination was performed to assess their periodontal and oral health status. The Kruskal-Wallis test was used to determine the statistically significant difference in the levels of periodontal oral fluid biomarkers between the different periodontitis stages, periodontitis grades, and the stages and grades of periodontitis combined. Spearman's rank correlation was performed to assess the strength and direction of the association between aMMP-8 and HbA1c levels (<5.7 and ≥5.7%) and with the other oral fluid biomarkers among patients with severe periodontitis. A two-sided p-value below 0.05 was considered statistically significant in this study. aMMP-8, but not total MMP-8 or other biomarkers, associated significantly with the stage and grade of periodontitis combined (p < 0.001, Kruskal-Wallis test). Among stage III grade C periodontitis patients, aMMP-8 levels were significantly positively correlated with prediabetes (Spearman's rho = 0.646, p = 0.044), total MMP-8 (rho = 0.636, p = 0.048), PMN Elastase (rho = 0.729, p = 0.017), total MMP-9 (rho = 0.721, p = 0.019), and total MMP-8/TIMP-1 molar ratio (rho = 0.879, p < 0.001). Prediabetic disease development can upregulate MMP-8 expression (total MMP-8) in rapidly progressing, severe periodontitis, where MMP-8 latent species are further activated into their active forms (aMMP-8). Simultaneously, several proinflammatory biomarker levels are elevated in this tissue-destructive biomarker cascade. This development is easily detectable online/in real-time within 5 minutes by aMMP-8 PoC testing at the dentist's office.

Effects of immunosuppression after limb fracture in mice on nociceptive, cognitive, and anxiety-related outcomes.

Chronic pain is a common and problematic consequence of injuries with few proven methods for prevention or treatment. In addition to pain, functional limitations and neuropsychiatric changes such as cognitive impairment and anxiety worsen outcomes. To determine whether inhibiting activation of the adaptive immune response after limb fracture would reduce pain, functional loss, memory changes, and anxiety. These experiments used a murine tibial fracture/cast immobilization model that develops these adverse outcomes. Adaptive immunity was blocked using the immunosuppressant FK506 beginning at the time of fracture. The administration of FK506 reduced mechanical allodynia and hind limb unweighting for weeks after cast removal as well as nonevoked pain measures. Fracture was associated with working memory loss in the Y-maze assay in vehicle- but not FK506-treated mice. Object recognition memory was not improved with FK506 after fracture. Also, vehicle- but not FK506-treated mice developed an anxiety phenotype. Impaired running wheel performance after cast removal over the following 2 weeks was not improved with FK506 administration. In addition, FK506 treatment blocked Immunoglobulin M (IgM) accumulation in the skin of the fractured limbs, and hippocampal enhancement of matrix metalloproteinase-8 expression, a metalloproteinase associated with neuroplastic changes after injuries, was completely blocked. Taken together, our results show that blocking the adaptive immune response after limb trauma reduces the severity of nociceptive and biological changes. The same treatment may reduce the adverse consequences of anxiety and memory deficits using some measures, but other measures of memory are not affected, and activity is not enhanced.

154 - Improved bladder contraction after CrisprCas9-mediated deletion of matrix metalloproteinase-9 in female prediabetic TallyHo mice

154 - Improved bladder contraction after CrisprCas9-mediated deletion of matrix metalloproteinase-9 in female prediabetic TallyHo mice

The Role of Biomarkers in Predicting Outcomes of Anterior Cruciate Ligament Reconstruction: A Systematic Review.

Anterior cruciate ligament (ACL) injury is frequently associated with injuries to other parts of the knee, including the menisci and articular cartilage. After ACL injury and reconstruction, there may be progressive chondral degradation. Biomarkers in blood, urine, and synovial fluid can be measured after ACL injury and reconstruction and have been proposed as a means of measuring the associated cellular changes occurring in the knee. To systematically review the literature regarding biomarkers in urine, serum, or synovial fluid that have been associated with an outcome measure after ACL reconstruction. Systematic review; Level of evidence, 3. This review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The MEDLINE, Embase, CINAHL, and Web of Science databases were searched to identify studies published before September 2023 that reported on patients undergoing ACL reconstruction where a biomarker was measured and related to an outcome variable. Of 9360 results, 16 studies comprising 492 patients were included. Findings were reported as descriptive summaries synthesizing the available literature. A total of 45 unique biomarkers or biomarker ratios were investigated (12 serum, 3 urine, and 38 synovial fluid; 8 biomarkers were measured from >1 source). Nineteen different outcome measures were identified, including the International Knee Documentation Committee Subjective Knee Form, Knee injury and Osteoarthritis Outcome Score, numeric pain scores, radiological outcomes (magnetic resonance imaging and radiography), rates of arthrofibrosis and cyclops lesions, and gait biomechanics. Across the included studies, 17 biomarkers were found to have a statistically significant association (P < .05) with an outcome variable. Serum interleukin 6 (s-IL-6), serum and synovial fluid matrix metalloproteinase-3 (s-MMP-3 and sf-MMP-3), urinary and synovial fluid C-terminal telopeptide of type 2 collagen (u-CTX-II and sf-CTX-II), and serum collagen type 2 cleavage product (s-C2C) showed promise in predicting outcomes after ACL reconstruction, specifically regarding patient-reported outcome measures (s-IL-6 and u-CTX-II), gait biomechanical parameters (s-IL-6, sf-MMP-3, s-MMP-3, and s-C2C), pain (s-IL-6 and u-CTX-II), and radiological osteoarthritis (ratio of u-CTX-II to serum procollagen 2 C-propeptide). The results highlight several biomarkers that have been associated with clinically important postoperative outcome measures and may warrant further research to understand if they can provide meaningful information in the clinical environment.

Balancing Relief and Pain: Effects of COX-2 Inhibitor Valdecoxib

Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, was initially acclaimed for its gastrointestinal safety and effectiveness in managing chronic inflammatory conditions and pain. It reduced gastrointestinal complications compared to other anti-inflammatory drugs, benefiting patients with complex medication regimens. The injectable form, parecoxib, was seen as promising for acute post-surgery pain management. However, clinical trials in high-risk cardiovascular patients, particularly those undergoing coronary artery bypass grafting, revealed increased risks when using higher doses of parecoxib. These findings led to the re-evaluation of valdecoxib’s safety profile and its subsequent market withdrawal due to cardiovascular concerns and reports of serious skin reactions. Despite its withdrawal, valdecoxib has garnered interest for repurposing in other conditions. Its pharmacodynamic and pharmacokinetic properties suggest potential in qualifying palmitate-induced insulin resistance in type 2 diabetes and inhibiting matrix metalloproteinases for wound healing. Its efficacy against SARS-CoV-2 highlights drug repurposing strategies for health crises like COVID-19. Valdecoxib's established success in arthritis, dysmenorrhea, and postoperative pain, along with its potential in treating glaucoma, underscores the value of repurposing existing drugs for new therapeutic purposes. In conclusion, valdecoxib exemplifies the balance between drug safety, clinical utility, and innovative repurposing. The aim of this study is to fully harness drug potential in medical science through a concerted effort made by the scientific community, regulatory bodies, and industry stakeholders to navigate the technological and regulatory hurdles.

Actinidia chinensis polysaccharide interferes with the epithelial-mesenchymal transition of gastric cancer by regulating the nuclear transcription factor-κB pathway to inhibit invasion and metastasis.

To investigate the mechanisms of the effect of Actinidia chinensis polysaccharide (ACPS) on the invasion and metastasis of gastric cancer cells. BGC-823-Luc gastric cancer cells stably transfected with a luciferase gene were used to establish an insitutransplanted tumor mouse model. A live mouse imaging system was used to observe tumor growth, and hematoxylin and eosin staining was applied to analyze tissue histopathology. Transwell and scratch wound assays were performed to examine the invasive and migratory ability of BGC-823 cells. Immunofluorescence, confocal microscopy, immunohistochemistry, and Western blot assays were used to analyze the expressions of the nuclear transcription factor-κB (NF-κB) signaling pathway and epithelial-mesenchymal transition (EMT)-related proteins. ACPS significantly inhibited the growth of subcutaneously transplanted BGC-823-Luc gastric cancer tumors in nude mice and reduced inflammatory cell infiltration in tumor tissues. ACPS inhibited Epidermal Growth Factor-induced invasion, migration, and morphological changes in the cytoskeleton of BGC-823 cells. ACPS inhibited gastric cancer EMT and decreased the expression of matrix metallopeptidase 9, N-cadherin and p-NF-κB p65 in transplanted tumor tissues. ACPS inhibited the expression of matrix metalloproteinases and vascular adhesion factors in BGC-823 cells, promoted p65-NF-κB nuclear translocation, and regulated proteins associated with the NF-κB p65 pathway. ACPS inhibited gastric cancer invasion and metastasis both in vivo and in vitro, which evidenced the inhibition of gastric cancer EMT viaregulating the NF-κB inflammatory pathway.

A Novel Porcine Model of Thoracic Aortic Aneurysms Reveals Increased Endogenous Matrix Metalloproteinase Activity

A Novel Porcine Model of Thoracic Aortic Aneurysms Reveals Increased Endogenous Matrix Metalloproteinase Activity

Heparanase-induced endothelial glycocalyx degradation exacerbates lung ischemia/reperfusion injury in male mice.

The endothelial glycocalyx (eGC) is a carbohydrate-rich layer on the vascular endothelium, and its damage can lead to endothelial and organ dysfunction. Heparanase (HPSE) degrades the eGC in response to cellular stress, but its role in organ dysfunction remains unclear. This study investigates HPSE's role in lung ischemia-reperfusion (I/R) injury. A left lung hilar occlusion model was used in B6 wildtype (WT) and HPSE genetic knockout (-/-) mice to induce I/R injury invivo. The left lungs were ischemic for 1 h followed by reperfusion for 4 h prior to investigations of lung function and eGC status. Data were compared between uninjured lungs and I/R-injured lungs in WT and HPSE-/- mice. WT lungs showed significant functional impairment after I/R injury, whereas HPSE-/- lungs did not. Inhibition or knockout of HPSE prevented eGC damage, inflammation, and cellular migration after I/R injury by reducing matrix metalloproteinase activities. HPSE-/- mice exhibited compensatory regulation of related gene expressions. HPSE facilitates eGC degradation leading to inflammation and impaired lung function after I/R injury. HPSE may be a therapeutic target to attenuate graft damage in lung transplantation.

Effect of matrix metalloproteinase inhibitors on microtensile bond strength to dentin using self-etch adhesive - in vivo study

Effect of matrix metalloproteinase inhibitors on microtensile bond strength to dentin using self-etch adhesive - in vivo study

Matrix Metalloproteinase Inhibition in Rat Abdominal Aortic Aneurysm

Matrix Metalloproteinase Inhibition in Rat Abdominal Aortic Aneurysm

Metformin represses the carcinogenesis potentially induced by 50 Hz magnetic fields in aged mouse fibroblasts via inhibition of NF-kB.

Aging is a risk factor for various human disorders, including cancer. Current literature advocates that the primary principles of aging depend on the endogenous stress-induced DNA damage caused by reactive oxygen species 50 Hz low-frequency magnetic field was suggested to induce DNA damage and chromosomal instability. NF-kB, activated by DNA damage, is upregulated in age-related cancers and inhibition of NF-kB results in aging-related delayed pathologies. Metformin (Met), an NF-kB inhibitor, significantly reduces both NF-kB activation and expression in aging and cancer. This invitro study, therefore, was set out to assess the effects of 5mT MF in 50 Hz frequency and Met treatment on the viability and proliferation of aged mouse NIH/3T3 fibroblasts and expression of RELA/p65, matrix metalloproteinases MMP2 and MMP9, and E-cadherin (CDH1) genes. The trypan blue exclusion assay was used to determine cell viability and the BrdU incorporation assay to determine cell proliferation. The MMP-2/9 protein analysis was carried out by immunocytochemistry, NF-kB activity by ELISA and the expressions of targeted genes by qRT-PCR methods. Four doses of Met (500 uM, 1 mM, 2 mM and 10 mM) suppressed both the proliferation and viability of fibroblasts exposed to the MF in a dose-dependent pattern, and the peak inhibition was recorded at the 10 mM dose. Met reduced the expression of NF-kB, and MMP2/9, elevated CDH1 expression and suppressed NF-kB activity. These findings suggest that Met treatment suppresses the carcinogenic potential of 50 Hz MFs in aged mouse fibroblasts, possibly through modulation of NF-kB activation and epithelial-mesenchymal transition modulation.

Moringa oleifera leaf extract ameliorates collagen degradation via the inhibition of MMP‐3 expression in UVB‐induced rats

Prolonged exposure to high‐intensity UVB induces the formation of reactive oxygen species (ROS) in skin tissue, triggering an increase in matrix metalloproteinase‐3 (MMP‐3) enzyme production and leading to collagen degradation. Moringa oleifera (MO) contains bioactive compounds known for ROS‐scavenging and anti‐inflammatory properties. However, the precise molecular mechanism of action remains unclear, requiring the inhibition of MMP‐3 activation and regulation of collagen deposition. This study aims to elucidate the potential effect of MO leaf extract‐based gel in restoring collagen deposition by reducing MMP‐3 activation in UVB irradiate‐induced collagen loss in rats. This study employed a completely randomized design, comprising four groups: a healthy group without UVB radiation, a negative control group subjected to UVB radiation and receiving a placebo, and two treatment groups exposed to UVB radiation with 5% or 10% moringa leaf extract‐based gel (MO‐5% or MO‐10%), respectively. Results showed that MO‐5% and MO‐10% significantly reduced MMP‐3 gene expression and increased collagen density compared to the negative control group (p &lt; 0.05). Moringa oleifera leaf extract ameliorates collagen degradation by inhibiting MMP‐3 expression in UVB‐induced rats, suggesting its potential as a pharmacological and cosmetic agent for UVB‐induced skin damage.

Impacts of Matrix Metalloproteinase-8 Genotypes, Smoking, Alcohol Drinking, and Helicobacter Pylori Infection on Gastric Cancer.

In gastric cancer (GCa) tissues, mRNA expression of matrix metalloproteinase-8 (MMP-8) is notably reduced compared to healthy tissues. Furthermore, abnormally low or elevated serum levels of MMP-8 have been linked to a significantly poor prognosis. The involvement of MMP-8 genotypes in susceptibility to GCa remains underexplored. We aimed to assess the influence of MMP-8 genotypes on GCa susceptibility and their potential interactions with smoking, alcohol consumption, and Helicobacter pylori (H. pylori) infection. The study utilized polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) to analyze MMP-8 rs11225395, rs34009635, and rs35866072 genotypes in 161 GCa patients and 483 controls. No statistically significant difference was detected in the distribution of genotypic (p for trend=0.3635) or allelic (p=0.1954) frequencies of MMP-8 rs11225395. Under a dominant model, combined CT+TT genotypes showed no association with GCa risk [odds ratio (OR)=0.77, 95% confidence interval (95%CI)=0.54-1.10, p=0.1852]. Similarly, no association was observed for MMP-8 rs34009635 or rs35866072. Importantly, individuals with the MMP-8 rs11225395 CC genotype demonstrated a significant increase in GCa risk when exposed to smoking (OR=4.04, 95%CI=2.28-7.16, p=0.0001), alcohol consumption (OR=2.83, 95%CI=1.64-4.89, p=0.0002), and H. pylori infection (OR=3.53, 95%CI=2.12-5.90, p=0.0001). The findings indicate that individuals carrying the MMP-8 rs11225395 CC genotype have increased susceptibility to GCa, especially when combined with risk factors, such as smoking, alcohol consumption, and H. pylori infection. These results suggest that MMP-8 genotype-based preventive strategies, including lifestyle alterations and targeted infection treatments, may be valuable in mitigating GCa development.

A molecular docking insight: Phyllanthus niruri L. constituents targeting MMP-9 for angiogenesis inhibition and IL-1beta for antiinflammatory action in endometriosis therapy

Endometriosis, characterized by inflammatory lesions resembling endometrium outside the uterine cavity, induces chronic inflammation, anatomical changes and persistent pain. The expression of Interleukin 1beta (IL-1beta) is significantly associated with endometriosis, contributing to inflammatory process and fertility issues. Matrix metalloproteinase 9 (MMP-9) is crucial in the adhesion and angiogenesis of endometrial tissue. This study investigates the potential of Phyllanthus niruri L. in inhibiting MMP-9 and IL-1beta through molecular docking analysis. Molecular docking was performed using Discovery Studio Visualizer, Open Babel, PyRx and AutoDock Vina. The inhibitory activities of bioactive compounds on MMP-9 and IL-1beta were predicted. Biological activity and cytotoxicity were assessed using PASS and CLC-Pred respectively. Kaempferol and quercetin from P. niruri exhibited significant MMP-9 expression inhibitory activity. Search Tool for Interacting Chemicals (STITCH) analysis revealed interactions of quercetin and galangin with specific proteins involved in pathways related to endometriosis. Biological activity analysis indicated that quercetin, kaempferol, herbacetin and galangin show potential as MMP -9 expression inhibitors. CLC-Pred analysis suggested high cytotoxicity of kaempferol against glioma. Molecular docking results showed quercetin's potential as an MMP-9 inhibitor and galangin's potential as an IL-1 beta inhibitor. These findings support the therapeutic potential of P. niruri for endometriosis, providing insights for further research in developing innovative therapies targeting endometriosis-related inflammation and angiogenesis.

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.

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.

Omega-3 Polyunsaturated Fatty Acids and Blood-Brain Barrier Integrity in Major Depressive Disorder: Restoring Balance for Neuroinflammation and Neuroprotection.

Major depressive disorder (MDD), affecting over 264 million individuals globally, is associated with immune system dysregulation and chronic neuroinflammation, potentially linked to neurodegenerative processes. This review examines blood-brain barrier (BBB) dysfunction in MDD, focusing on key regulators like matrix metalloproteinase 9 (MMP9), aquaporin-4 (AQP4), and ATP-binding cassette subfamily B member 1 (ABCB1). We explore potential mechanisms by which compromised BBB integrity in MDD may contribute to neuroinflammation and discuss the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs). n-3 PUFAs have demonstrated anti-inflammatory and neuroprotective effects, and potential ability to modulate MMP9, AQP4, and ABCB1, thereby restoring BBB integrity in MDD. This review aims to elucidate these potential mechanisms and evaluate the evidence for n-3 PUFAs as a strategy to mitigate BBB dysfunction and neuroinflammation in MDD.

Oral and Gingival Crevicular Fluid Biomarkers for Jawbone Turnover Diseases: A Scoping Review

Gingival crevicular fluid (GCF) and oral fluid have emerged as promising diagnostic tools for detecting biomarkers. This review aimed to evaluate the existing literature on using oral fluids as a source of biomarkers for bone turnover diseases affecting the jawbone. A comprehensive search strategy was executed between August 2014 and August 2024 across five major databases (Web of Science, EBSCOhost Dentistry &amp; Oral Sciences Source, Cochrane Library, Scopus, and PubMed) and grey literature sources. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was applied. The screening was facilitated using Rayyan at rayyan.ai and Endnote X20 software tools, culminating in the evaluation of 14,965 citations from databases and 34 from grey literature. Following rigorous scrutiny, 37 articles were selected for inclusion in this review, encompassing diseases such as periodontitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoporosis. The quality of the included observational studies was assessed using the Revised Risk of Bias Assessment Tool for Non-Randomized Studies (RoBANS 2). Interleukin-1 beta (IL-1β), sclerostin, osteoprotegerin (OPG), and interleukin-34 (IL-34) emerged as significant biomarkers in GCF, and they were mainly from periodontitis and osteoporosis. Osteocalcin (OC), IL-1β, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), OPG, and matrix metalloproteinase-9 (MMP-9) were significant in oral fluid or saliva, and they were from periodontitis, MRONJ, and osteoporosis. These findings underscore the potential use of oral fluids, which are regarded as non-invasive tools for biomarker identification in bone turnover. Many biomarkers overlap, and it is important to identify other specific biomarkers to enable accurate diagnosis of these conditions.