Matrix Metalloproteinase-9 Levels Research Articles

Impact of Berberine Hydrochloride-assisted Metformin on the Metabolism of Glycolipids and Serum Levels of TIMP-1 and TGF-β1 in Individuals with Type 2 Diabetes

Background Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and impaired glucose metabolism, leading to hyperglycemia and increased risk of complications like renal fibrosis. Purpose This study’s purpose is to examine how berberine hydrochloride (BBR) and metformin (Met) work together to treat T2DM, as well as how these medications affect tissue type metalloproteinase-1 (TIMP-1), glucose, and lipid metabolism levels in the blood and transforming growth factor β1. Methods Using a random number table approach, overall, 100 individuals with T2DM between October 2020 and October 2022 were chosen and classified into two groups: An experimental group and an untreated group, each with 50 patients. The untreated group received Met therapy, whereas the experimental group received BBR based on the untreated group. The two groups were compared regarding efficacy, cholesterol and glucose metabolism, renal function and renal fibrosis indices, and the frequency of adverse responses. Results The experimental group’s effective rate was 96.00% higher than that of the untreated group (82.00%). Following treatment, the experimental group had lower levels of glycosylated hemoglobin (HbAlc), insulin resistance index (HOMA-IR), fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and cholesterol (TC) than the untreated group, while the untreated group had greater levels of high-density lipoprotein cholesterol (HDL-C). Following the course of therapy, the observation group’s levels of cystatin (Cys-C), urinary β2 microglobulin (β2-MG), urine albumin excretion rate (UAER), and urinary microalbumin (ALB) were all lesser compared to the untreated group. Following treatment, the experimental group’s transforming growth factor-β (TGF-β) levels, matrix metalloproteinase-9 (MMP-9), and TIMP-1 were lesser than those of the untreated group. Conclusion When Met and BBR are taken together, patients with type 2 diabetes can effectively control their glucose and lipid metabolism, as well as their levels of TGF-β1, MMP-9, and TIMP-1. They can also postpone renal interstitial fibrosis and eventually improve their kidney function, all with a high degree of safety and significant effects.

Xuefu Zhuyu Decoction Improves Blood-Brain Barrier Integrity in Acute Traumatic Brain Injury Rats via Regulating Adenosine.

To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.

Autocatalytic Ceria Nanoparticle-Embedded Tilapia Collagen Hydrogels as Enhanced Antioxidative and Long-Lasting Dermal Fillers for Photoaged Skin.

Excessive reactive oxygen species (ROS) generated by ultraviolet (UV) irradiation significantly contribute to photoaging by increasing the level of matrix metalloproteinases (MMPs), accelerating collagen degradation. Commercial dermal fillers offer temporary wrinkle reduction via volume enhancement. In this study, we propose tilapia-derived collagen hydrogels embedded with ceria nanoparticles (Ce@Col gels) as long-lasting dermal fillers for UVB-induced photoaging. Ceria nanoparticles (CeNPs) significantly enhance the stability of the collagen matrix against enzymatic degradation. These gels exhibit mechanical stability and injectability comparable to those of commercial alternatives. Additionally, CeNPs effectively eliminate ROS to suppress MMP production, curbing both collagen degradation and inflammatory responses. In a UVB-induced photoaging mouse model, the Ce@Col gels significantly reduced the level of oxidative stress in the skin, decreased the number of wrinkles, reduced epidermal thickness, and decreased levels of aging-related biomarkers while increasing the level of collagen deposition. These antiaging effects persisted for seven months post-injection, highlighting Ce@Col gels as a promising approach for prolonged collagen regeneration and sustained anti-inflammatory benefits in photoaged skin.

Exploring the Causal Relationship Between the Plasma Levels of MMP1 (Matrix Metalloproteinase-1), MMP3, MMP7, MMP10, and MMP12 and Intervertebral Disc Degeneration: Mendelian Randomization.

Several matrix metalloproteinases (MMPs) have been reported to be associated with intervertebral disc degeneration (IDD) in several previous studies. However, the causal relationship between MMPs and IDD remains unclear. In this study, Mendelian randomization (MR) was used to analyze the causal relationship between the plasma levels of multiple MMPs and the risk of IDD. The GWAS data of the plasma levels of MMP1, MMP3, MMP7, MMP10, and MMP12 were derived from the genome-wide variation associations of 21 758 European individuals. The genetic associations of the variants with IDD were investigated in the largest genome-wide association study from GWAS pipeline using Phesant derived variables from UKBiobank (1045 cases; 461 965 controls). We used a two-sample MR method to evaluate the causal relationship between these five MMPs and IDD. The causal effects were examined by inverse variance weighted (IVW) test. And sensitivity analysis was performed using Q test of IVW and MR-Egger, MR-Egger-intercept and MR-PRESSO. We found a significant correlation between increased the plasma level of MMP3 and an increased risk of IDD (IVW: OR 1.000564, 95% CI 1.0000304-1.00110; p = 0.0383). The heterogeneity test (MR-Egger Q test: p = 0.346 and IVW Q test: p = 0.460) indicated that there was no heterogeneity in this instrumental variable on the surface. Also, no directional horizontal pleiotropy was observed in the MR analysis (MR-Egger, p = 0.708 and MR-PRESSO, p = 0.609). There was no significant correlation between the plasma levels of MMP1, MMP7, MMP10, and MMP12 and an increased risk of IDD. Our MR analysis found that there is a potential causal relationship between increased the plasma level of MMP3 and the risk of IDD in the European population. There is no potential causal relationship between the plasma levels of MMP1, MMP7, MMP10, and MMP12 and an increased risk of IDD.

Clinical Significance of Serum MMP-9, S100-β and GFAP in Patients with Mental Disorders after Traumatic Brain Injury.

Diagnosing psychiatric disorders following craniocerebral trauma primarily depends on clinical symptoms and neuropsychological evaluation, which can be subjective and limited. This study aimed to investigate the diagnostic value of serum matrix metalloproteinase-9 (MMP-9), S100 calcium-binding protein β (S100-β), and glial fibrillary acidic protein (GFAP) in post-traumatic mental disorders. A retrospective analysis was conducted on 108 patients with craniocerebral trauma admitted to Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine between January 2021 and December 2023. Patients were categorized into a post-traumatic mental disorder group (n = 68) and a simple craniocerebral trauma group (n = 40) according to whether they had mental disorders. Serum MMP-9, S100-β, and GFAP levels were measured using enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Logistic multivariate regression identified risk factors for post-traumatic mental disorders, while receiver operating characteristic (ROC) curve analysis assessed the predictive value of the biomarkers. Spearman correlation analysis examined the relationship between serum biomarkers and the presence of post-traumatic mental disorders. Serum levels of MMP-9, S100-β, and GFAP were significantly elevated in the post-traumatic mental disorder group compared to the simple traumatic brain injury group (p < 0.001). Logistic regression revealed that craniocerebral injury severity, family satisfaction, and serum levels of S100-β and GFAP were significant risk factors for post-traumatic mental disorders (p < 0.05). The areas under the ROC curve for MMP-9, S100-β, and GFAP were 0.768, 0.937, and 0.904, respectively. Spearman correlation analysis showed that serum MMP-9, S100-β and GFAP were significantly positively correlated with the incidence of post-traumatic mental disorders (p < 0.001). The levels of MMP-9, S100-β and GFAP were abnormal in the serum of patients with craniocerebral trauma. These biomarkers hold significant diagnostic value in patients with post-traumatic stress disorder.

Eugenol inhibits NEAT1 as a ceRNA in pre-cancerous breast lesions.

Eugenol (EU) from cloves is highly effective against different tumors. The long noncoding ribonucleic acids (lncRNAs), which play a role of competing endogenous RNAs (ceRNAs), suppress microRNAs (miRNAs) involved in post-transcriptional regulatory networks. The present work focused on analyzing how EU affected pre-cancerous breast lesions (PBL). Initially, the gene expression profiles of patients (n=880) in the National Center for Biotechnology Information (NCBI) database were analyzed. Further, we established a lncRNA-miRNA-mRNA ceRNA network through bioinformatics analysis and investigated mechanistic roles of lncRNAs as ceRNAs and the anti-tumor effect of EU using MCF-10AT cells in vitro as well as PBL model rats in vivo. Besides, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), miR-383-5p, miR-9-5p, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A) expression was examined through quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemical staining analyses. There were altogether 1162 mRNAs, 81 miRNAs, and 26 lncRNAs recognized as trend genes in breast cancer (BC) and pre-cancerous BC (pBC), constructing the ceRNA network using 3 lncRNAs, 3 miRNAs, and 38 mRNAs. It was observed that NEAT1, miR-383-5p, miR-9-5p, VEGF-A, and MMP-9 were downregulated in breast tumor cells in accordance with bioinformatics analysis. EU suppressed MCF-10AT cell growth, decreasing the NEAT1, VEGF-A, and MMP-9 levels and increasing miR-383-5p and miR-9-5p expressions in vitro and in vivo. In summary, the EU reduced the VEGF-A and MMP-9 expressions via NEAT1-mediated miR-383-5p and miR-9-5p against PBL, indicating that the EU may be a promising external drug to act against PBL.

YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12.

Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area. The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9-11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes. HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Tumor Microenvironment Responsive Key Nanomicelles for Effective Against Invasion and Metastasis in Ovarian Cancer Using Mice Model.

Ovarian cancer is difficult to detect in its early stages, and it has a high potential for invasion and metastasis, along with a high rate of recurrence. These factors contribute to the poor prognosis and reduced survival times for patients with this disease. The effectiveness of conventional chemoradiotherapy remains limited. Nano-particles, as a novel drug delivery system, have significant potential for improving therapeutic efficacy and overcoming these challenges. According to the high expression level of matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, MMP-2 responsive nano-particles (PVGLIG-MTX-D/T-NMs) containing docetaxel and triptolide were prepared by the thin-film dispersion method. The synergistic effect between docetaxel and triptolide was systematically investigated, the ratio of the two drugs was optimized, and the physicochemical properties of the nano-particles and their ability to inhibit ovarian cancer cell growth and metastasis were evaluated in vitro and in vivo. PVGLIG-MTX-D/T-NMs enhanced the targeting, stability, and bioavailability of the drug, while reducing the dose and toxicity. In addition, by regulating the expression levels of E-Cadherin, N-Cadherin, matrix metalloproteinases (MMPs), hypoxia-inducible factor 1-alpha (HIF-1α), and vascular endothelial growth factor (VEGF), it exhibited an inhibitory effect on epithelial-mesenchymal transformation (EMT) and tumor cell angiogenesis, and effectively inhibited the invasion and metastasis of ovarian cancer cells. PVGLIG-MTX-D/T-NMs achieved passive targeting of tumor sites by enhancing permeability and retention (EPR) effects. Subsequently, the uptake of the drug by tumor cells was enhanced by MMP-2 responsiveness and the modification of methotrexate targeting ligands. By regulating the expression levels of invasion- and metastasis-related proteins in tumor tissues, the nano-particles affected the EMT process, inhibited tumor angiogenesis, and suppressed the malignant potential of invasion and metastasis in ovarian cancer. These findings provided a new direction for further exploration of tumor-targeted therapy.

Exploring the remarkable effect of ursodeoxycholic acid and Allium sativum combination on MMP-9 and TIMP-1 levels in cholestatic rat’s model

Background: Cholestasis is a disturbance in the production or flow of bile that causes excessive accumulation of bile fluid and damage in the liver. Chronic liver damage will lead to liver fibrosis. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloprotease-1 (TIMP-1) play a critical role in liver fibrosis formation. Although ursodeoxycholic acid (UDCA) and Allium sativum extracts have long been renowned for improving liver function, their combination in alleviating liver fibrosis through the MMP-9 and TIMP-1 inhibitory pathways has yet to be studied.Objective: This study was conducted to assess the efficacy of UDCA and Allium sativum extract combination in altering MMP-9 and TIMP-1 levels, which are the main factors in the progression of liver fibrosis.Methods: We performed an experimental study with a post-test-only control group on 36 Sprague-Dawley rats, which were randomly grouped into healthy, negative, positive, and three treatment groups with UDCA (13.5 mg) and graded doses of Allium sativum extract (3.6 mg; 7.2 mg; and 14.4 mg). Cholestasis induction was done by a choledochal duct ligation, and treatment was given for 14 days. Levels of MMP-9 and TIMP-1 were analyzed after treatment.Results: Combining UDCA and Allium sativum improved the MMP-9 levels significantly in cholestatic rats, compared to administrating UDCA only (p &lt;0.05). Combining UDCA and Allium sativum increased the TIMP-1 level (p &lt; 0.05). Although the MMP-9 level results were under our existing hypothesis, TIMP-1 results showed surprising results. Matrix metalloproteinase-9 levels were strongly negatively correlated with TIMP-1 levels, with a r-value= 0.981.Conclusion: Combining Allium sativum and UDCA alleviates liver fibrosis progression through lowering levels of MMP-9 and increasing levels of TIMP-1.

The Influence of Bariatric Surgery on Matrix Metalloproteinase Plasma Levels in Patients with Type 2 Diabetes Mellitus.

Bariatric surgery is a safe and effective procedure for treating obesity and metabolic conditions such as type 2 diabetes mellitus (T2DM). Remodeling of the extracellular matrix (ECM) supports adipose tissue expansion and its metabolic activity, where matrix metalloproteinases (MMPs) play a key role in ECM regulation. The MMPs, particularly MMP-2 and MMP-9, are elevated in patients with morbid obesity, metabolic syndrome, and T2DM. To evaluate the effect of weight loss in bariatric surgery patients using oxidative stress markers and to compare MMP levels in patients undergoing bariatric surgery. This was a prospective, controlled study including 45 morbidly obese patients with T2DM (BMI > 35 kg/m2) who underwent RYGB (n = 24) or VG (n = 21). Weight loss was assessed through anthropometric measurements (weight, height, BMI). MMP-2 and MMP-9 levels were measured preoperatively and at 3 and 12 months postoperatively. Significant and sustained weight loss was observed after surgery in both groups, with reductions in BMI. MMP-2 and MMP-9 levels decreased significantly after one year of follow-up. Bariatric surgery is an effective long-term intervention for weight loss and associated comorbidities, including T2DM. MMP-2 and MMP-9 proved to be effective markers of extracellular matrix remodeling, with significant reductions following surgery.

Expression of lipid metabolism and cartilage degeneration-related factors in lumbar vertebral endplate Modic changes.

This study aims to investigate the relationship between the expression of lipid metabolism and cartilage degeneration-related factors and Modic changes (MCs) of lumbar vertebral. This prospective study included a total of 10 patients (6 males, 4 females; mean age: 60.4±8.7 years; range 51 to 82 years) who underwent lumbar interbody fusion surgery due to degenerative lumbar diseases (MC group), and 10 control patients (4 males, 6 females; mean age: 49.7±9.8 years; range, 42 to 76 years) with lumbar burst fractures (nonMC group) between January 2020 and December 2022. Clinical imaging data and cartilage tissues were collected to observe cartilage characteristics and pathological changes. The relative expression levels of lipid metabolism-related inflammatory factors matrix metalloproteinase-1 (MMP-1), a disintegrin and metalloproteinase with thromboSpondin motifs-5 (ADAMTS-5), and aggrecan in cartilage were detected by quantitative polymerase chain reaction (qPCR). The relative expression levels of MMP-1 and ADAMTS-5 proteins in cartilage tissues were detected by Western blotting. There were no significant differences in the baseline characteristics between the two groups. The color and transparency of the endplate cartilage in the control group were significantly better than those in the MCs group. Radiographic and hematoxylin-eosin staining of the endplate cartilage tissues showed that the extracellular matrix was higher in the control group than in the MCs group (p<0.05). Compared to the control group, qPCR analysis showed higher expression of MMP-1 and ADAMTS-5 in the MCs group, while aggrecan expression was lower (p<0.05). Western blot analysis showed that both MMP-1 and ADAMTS-5 expression were higher in the MCs group than in the control group (p<0.05). Lipid metabolism and cartilage degeneration-related inflammatory factors exist in the vertebral endplate of the patients with degenerative lumbar diseases, and the upregulation of MMP-1 and ADAMTS-5 may be related to MCs and endplate degeneration.

Photoprotective effects of quercetin on photoaging-induced rats

Purpose Photoaging is characterised by cutaneous changes caused by exposure to ultraviolet light over time. Quercetin is a bioflavanoid with antioxidant, antineoplastic, and anti-inflammatory effects. This study investigated the therapeutic effects of topical quercetin on photoaging, a phenomenon not previously studied in ultraviolet A (UVA)-induced photoaging. Methods A total of 40 rats were randomly categorised into 5 groups, each comprising 8 rats. A photoaging model was induced by applying UVA to the dorsal region of all rats, except for the negative control group. Topical 0.1% retinoic acid was applied to one UVA group, topical 0.3% quercetin to another UVA group, and both agents were applied in combination to yet another UVA group 5 days a week for 8 weeks. Subsequently, wrinkle values were measured, reactive oxygen species (ROS) and matrix metalloproteinase-1 (MMP-1) levels were analysed, and histopathological parameters were examined. Results The wrinkle value of the UVA group was found to be significantly higher than that of the UVA + Quercetin group. Collagen damage was lower in the UVA + Quercetin group than in the UVA group, although this difference was not statistically significant. Compared with the UVA + Retinoic Acid group, the UVA + Quercetin group exhibited a more significant decrease in inflammation. MMP-1 values were considerably higher in the UVA + Retinoic Acid and UVA + Quercetin + Retinoic Acid groups as well as in the UVA + Quercetin group compared with the control and UVA groups. Conclusion The present study showed that quercetin can be utilised in the treatment of photoaging, especially when combined with retinoic acid.

Plasma gelsolin and matrix metalloproteinase-3 levels as diagnostic markers for psoriatic arthritis

Recent studies have revealed a high prevalence of undiagnosed psoriatic arthritis (PsA) in patients with psoriasis. Diagnosis of psoriatic arthritis has proven challenging because the symptoms of the disease are nonspecific, rheumatoid factor is not detectable, and acute phase reactant levels may be normal. Therefore, identifying soluble biomarkers for diagnosing PsA in psoriasis patients may help in early diagnosis and proper management. The aim of the work was to evaluate plasma gelsolin and matrix metalloproteinase-3 (MMP-3) levels as potential markers for PsA. This case-control study included 25 healthy controls and 50 psoriasis patients, who were divided into 25 patients with psoriasis only and 25 patients with psoriatic arthritis. Plasma levels of gelsolin and MMP-3 were measured using ELISA. It was shown that patients with PsA had significantly lower gelsolin and significantly higher MMP-3 plasma levels compared to patients with psoriasis only. For detecting PsA, gelsolin and MMP-3 had sensitivity of 96% and specificity of 92 and 80% for each, respectively. Gelsolin level negatively while MMP-3 level positively correlated with such parameters­ as disease activity for psoriatic arthritis, composite psoriatic disease activity index, and inflammatory markers­ including high-sensitivity C-reactive protein and erythrocyte sedimentation rate. It was concluded that plasma gelsolin and MMP-3 levels could serve as potential biomarkers for diagnosing PsA and monitoring the disease progression in PsA patients. Keywords: gelsolin, MMP-3, psoriasis, psoriatic arthritis

MMP-3 and TIMP-1 as prognostic biomarkers in VZV-induced retinal necrosis.

Acute retinal necrosis (ARN) caused by varicella-zoster virus (VZV) is associated with changes in specific proteins in the eye's fluid, particularly matrix metalloproteinase-3 (MMP-3), an enzyme that breaks down tissue structures, and tissue inhibitor of metalloproteinase-1 (TIMP-1), which regulates MMP activity. This study aims to investigate how these proteins correlate with the progression of ARN. We analyzed aqueous humor samples from 33 patients with ARN and 23 control patients with virus-negative uveitis. MMP-3 levels were measured using immunoturbidimetry, and TIMP-1 levels were determined using an enzyme-linked immunosorbent assay. We examined the relationships between these protein levels and clinical findings using statistical correlation methods. MMP-3, TIMP-1 were significantly higher in the aqueous humor of ARN patients compared to the controls (P<0.0001). Correlation analysis revealed a significant correlation between MMP-3 levels and TIMP-1 (r = 0.460, P = 0.007). The upregulation of MMP-3 and TIMP-1 was found to parallel VZV DNA load and IL-6 levels. Additionally, they exhibited negative correlation with best corrected visual acuity (BCVA) and positive correlation with the percentage of active retinal necrosis area.MMP-3 was markedly enhanced in all 14 cases of retinal detachment (RD), whereas TIMP-1 levels were significantly reduced in the same cohort of eyes. Patients with initial higher TIMP-1 levels have a significantly increased risk of developing RD, with a hazard ratio (HR) of 3.152 (95% CI, 1.082-9.18). The imbalance between MMP-3 and TIMP-1 may play a critical role in the development and severity of ARN. Measuring these proteins in the eye's aqueous humor could be valuable for assessing disease progression and guiding treatment strategies, potentially improving outcomes for patients with virus-induced retinal diseases.

Derivatives of D(-)-glutamine-based MMP-2 inhibitors as an effective remedy for the management of chronic myeloid leukemia-Part-III: Synthesis, biological screening and in silico binding interaction analysis.

Tyrosine kinase inhibitors (TKIs) have markedly improved the overall survival rate of patients with chronic myeloid leukemia (CML), enabling them to achieve a normal life expectancy. However, toxicity, relapse, and drug resistance continue to pose major challenges in the clinical treatment of CML. The progression of leukemia is directly connected to higher expression levels and enzymatic actions of matrix metalloproteinase-2 (MMP-2). It is also associated with increased expression and enzymatic actions of matrix metalloproteinase-9 (MMP-9). From this perspective, MMP-2 and MMP-9 offers a promising strategy for developing novel therapeutic molecules that could be effective in treating CML. This study is the Part-III of D(-)-glutamine-based MMP-2 inhibitors series for the management of chronic myeloid leukemia. Fourteen newly synthesized p-tosyl-D(-)-glutamine derivatives were examined in cell culture-based antileukemic assays and also evaluated for their ability to inhibit MMPs. The lead compounds 5g and 5j demonstrated the most promising antileukemic potential. Compounds 5g and 5j are safe for normal cells and effectively block gelatinases (MMP-2 and MMP-9). The best active molecule 5g induced significant apoptosis. Compound 5g reduced MMP-2 levels in the K562 cell line. It also had strong antiangiogenic effects in the ACHN cell line. The strongest MMP-2 inhibitor, 5g, had stable binding at the MMP-2 active site, which is linked to its effective inhibition of MMP-2. In conclusion, these p-tosyl-D(-)-glutamine derivatives are promising MMP-2 inhibitors. They have strong anti-CML effects and should be studied more for future CML treatment.

Matrix Metalloproteinase-9 as a Predictor of Healing in Diabetic Foot Ulcers.

Background Wound healing in diabetic foot ulcers (DFUs) is hindered by several physiological and biochemical abnormalities, including prolonged inflammation, an imbalance in extracellular matrix (ECM) synthesis and degradation, insufficient neovascularization, and reduced macrophage activity. In DFUs, excessive and uncontrolled matrix metalloproteinases (MMPs) degrade the ECM and impede wound healing. Matrix metalloproteinase-9 (MMP-9) concentration plays a key role in inflammation and ECM degradation. This study explores the relationship between wound type in DFUs and MMP-9 levels, hypothesizing that a high MMP-9 environment may indicate inflammation and impaired wound healing. Materials and methods Forty individuals with type 2 diabetes and foot ulcers were recruited for the study. The participants were divided into two groups: nonhealing and healing, with 20 patients in each group. Biopsy samples were homogenized, and MMP-9 activity was measured using an ELISA. Results The MMP-9 concentration was significantly higher in nonhealing ulcers compared to healing ulcers. Receiver operating characteristic analysis revealed that MMP-9 measurement was the most accurate predictor of wound healing, with an area under the curve value of 0.945 and high sensitivity and specificity. Although there was a weak correlation between MMP-9 concentration and glycosylated hemoglobin, it was not statistically significant. Conclusions MMP-9 expression serves as a marker of poor wound healing. MMP-9 levels in the wound at the time of presentation may predict the healing trajectory and help tailor a specific treatment plan for each DFU patient.

EXTRACELLULAR MODULATORY AND ANTI-INFLAMMATORY EFFECTS OF A COMBIATION OF CURCUMIN, PIPERINE, AND VIRGIN COCONUT OIL IN ANIMAL MODEL

Objective: The current study investigated the potential of a novel herbal combination of curcumin, piperine, and virgin coconut oil to exhibit anti-inflammatory and anti-rheumatic properties against carrageenan-induced inflammation. Method: A minimal dose of the drug formulation having a maximal anti-inflammatory effect was found (Dose III). Following the completion of the experiment, the animals were humanely euthanized, and paw tissue and serum samples were collected for further analysis. The expression levels of mRNA for Tumor Necrosis Factor-alpha (TNF-α), interleukin (IL)-6, PGE-2, and Thiobarbituric acid reactive substance (TBARS), as activities of cyclooxygenase -2, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and TBARS were measured and levels of matrix metalloproteinases (MMP)9 and MMP2 were measured using zymography and western-blotting. Results: Anti-oxidant assays were performed in serum and synovial tissue, observed that the production of anti-oxidant enzymes such as SOD, GPx, CAT, and GSH was enhanced, and suppression of the accumulation of lipid peroxidation products in the group treated with the potent dose of the drug combination. A decrease in the mRNA expression of IL-6, IL-1β, and TNF α was noted in the treatment group, these are the upstream events of the inflammatory cascade. Radiological and histopathological analysis confirms that the drug formulation acted on MMPs to reduce its baneful consequence. Conclusion: The drug formulation’s anti-inflammatory and anti-rheumatic properties, combined with its multi-targeted mechanism, suggest its potential as a therapeutic agent for various inflammatory diseases.

Eucalyptol Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

Background One of the leading causes of acute brain injury is cerebral ischemia/reperfusion (I/R) injury. It is an ailment that occurs when the brain does not receive enough oxygen-rich blood supply, which damages brain cells. Oxidative stress is recognized as a significant mechanism that causes I/R injury and is a critical focal point for therapy. Apoptosis and inflammation are all pathogenic processes underpinning I/R damage. Eucalyptol (EU), a plant-derived substance, protects neuronal damage. We postulate that EU inhibits apoptosis and oxidative stress after focal cerebral I/R damage in mice. Purpose Thus, the present work sought to examine the neurological protective benefits of EU in mice models of cerebral ischemia/reperfusion (CI/R) injury. Methods The measurement of neurological function, infarct volume, and the amount of water in the brain were evaluated subsequently. The brain tissue was examined to assess the activities of oxidative stress, inflammatory cytokines, and matrix metalloproteinases (MMP) levels, and histopathology was determined. Using enzyme-linked immunosorbent assay (ELISA), apoptotic marker expression was used to measure the levels of B-cell lymphoma 2 (Bcl-2), caspase-3, and Bcl-2 associated X-protein (Bax) proteins that exist as indicators of apoptosis. Results EU treatment malondialdehyde (MDA) levels decreased while glutathione (GSH), superoxide dismutase (SOD), A-TOC, and catalase (CAT) activity increased. Following EU therapy dramatically reduced cerebral dysfunction, which was supported by reduced histological damage in I/R injury. Furthermore, with lower levels of MMP-2 and 9, EU treatment could be a novel approach for preventing CI/R injury. EU-treated mice had a notable reduction in cleaved Bax, caspase-3, and increased Bcl-2 protein activities. EU therapy shields the brain against CI/R injury by inhibiting cell death. Conclusion According to the present study’s findings, EU is a promising neuroprotective agent that can be used to treat CI/R injury in mice. By focusing on these aspects, nurses can provide comprehensive care to patients involved in studies on the effects of EU on CI/R injury, promoting better outcomes through careful monitoring, supportive interventions, and education.

Higher serum cystatin C and matrix metalloproteinase 9 levels effectively predict in-stent restenosis after stent implantation for intracranial and extracranial arterial stenosis

ObjectiveThis paper was performed to unravel the predictive value of serum cystatin C (Cys C) and matrix metalloproteinase 9 (MMP-9) levels before vascular stent implantation for in-stent restenosis (ISR) 6-12 months after stent implantation for intracranial and extracranial arterial stenosis. MethodsOne hundred and ninety-eight patients who underwent dilatation stenting for intracranial and extracranial arterial stenosis and completed Digital Subtraction Angiography or head and neck CT- Angiography review were selected for the study and were divided into ISR group (n = 33) and no ISR (NISR) group (n = 165) according to the presence or absence of ISR. Serum levels of Cys C, MMP-9, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), creatinine (Cr), homocysteine (Hcy), fibrinogen (FIB), total bilirubin (TBIL), endothelin-1 (ET-1), nitric oxide (NO), angiotensin II (Ang II), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) levels before vascular stent implantation were examined and compared between groups. ROC curves were employed for analyzing the predictive value of serum Cys C and MMP-9 alone or in combination for ISR. Pearson test was utilized for analyzing the serum Cys C and MMP-9 with vasoactive substances and inflammatory cytokines in patients in the ISR group. Logistic regression analysis was implemented to analyze the factors influencing ISR 6-12 months after stent implantation for intracranial and extracranial arterial stenosis. ResultsCys C, MMP-9, LDL, UA, Cr, Hcy, FIB, ET-1, NO, Ang II, IL-6, TNF-α, and CRP were higher in the ISR group than in the NISR group, and TBIL was lower than in the NISR group (P < 0.05). The AUC of the combined serum Cys C and MMP-9 (AUC = 0.900) was greater than that of Cys C (AUC = 0.685) or MMP-9 (AUC = 0.870) alone (P < 0.05). Cys C and MMP-9 levels were positively correlated with ET-1, NO, Ang II, IL-6, TNF-α, and CRP (r > 0, P < 0.05). Increased levels of Cys C, MMP-9, LDL-C, UA, Cr, Hcy, FIB, ET-1, NO, Ang II, IL-6, TNF-α, and CRP, and diabetes were risk factors for the development of ISR (OR > 1, P < 0.05), and TBil was protective factor (OR < 1, P < 0.05). ConclusionSerum Cys C combined with MMP-9 levels are effective in predicting ISR.

Zhuanggu Jianxi Decoction reduces synovial tissue inflammation in human knee osteoarthritis by regulating LXRs/NF-κB signaling pathway

This study aims to explore the mechanism of Zhuanggu Jianxi Decoction in reducing synovial tissue inflammation in human knee osteoarthritis(KOA) via the liver X receptors(LXRs)/nuclear factor(NF)-κB signaling pathway. The synovial tissue samples were collected from 5 healthy volunteers and 30 KOA synovitis patients and cultured in vitro. The samples from the heathy volunteers were set as the normal group, and those from KOA synovitis patients were randomized into synovitis, Zhuanggu Jianxi Decoction, LXRα inhibitor, and N-CoR inhibitor groups. The synovitis tissue samples of the 5 groups were treated with 10% blank serum, 10% blank serum, 10% drug-containing serum, 10% drug-containing serum+LXRα inhibitor, and 10% drug-containing serum+N-CoR inhibitor, respectively, for 7 days. After intervention, the synovial tissue samples of each group were collected and stained with hematoxylin-eosin for observation and scoring of the pathological changes. The expression intensity of the fibroblast-specific marker α-smooth musle actin(α-SMA) in the synovial tissue was observed by immunofluorescence staining. The levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase-13(MMP-13) in the supernatant of synovium homogenate were determined by ELISA. The mRNA and protein levels of LXRα, N-CoR, P50, and P65 in the synovial tissue were determined by RT-qPCR and Western blot, respectively. The results showed that compared with the normal group, the synovitis group showcased obvious synovial lining cell proliferation, inflammatory cell infiltration, synovial cell disarrangement, increased histopathological score(P&lt;0.05), enhanced α-SMA fluorescence intensity and increased number of synovial fibroblasts(P&lt;0.05), elevated levels of IL-1β, TNF-α, MMP-3, and MMP-13 in the synovial tissue(P&lt;0.05), down-regulated mRNA and protein levels of LXRα and N-CoR, and up-regulated mRNA and protein levels of P50 and P65(P&lt;0.05). Compared with the synovitis group, the Zhuanggu Jianxi Decoction group showed alleviated pathological changes, declined histopathological score of the synovial tissue(P&lt;0.05), decreased α-SMA fluorescence intensity and number of synovial fibroblasts(P&lt;0.05), lowered levels of IL-1β, TNF-α, MMP-3, and MMP-13(P&lt;0.05), up-regulated mRNA and protein levels of LXRα and N-CoR, and down-regulated mRNA and protein levels of P50 and P65(P&lt;0.05) in the synovial tissue. Compared with the Zhuanggu Jianxi Decoction group, the LXRα inhibitor group and N-CoR inhibitor group showed aggravated pathological changes, risen histopathological score of the synovial tissue(P&lt;0.05), enhanced α-SMA fluorescence intensity and increased number of synovial fibroblasts(P&lt;0.05), elevated levels of IL-1β, TNF-α, MMP-3, and MMP-13(P&lt;0.05), down-regulated mRNA and protein levels of LXRα and N-CoR, and up-regulated mRNA and protein levels of P50 and P65(P&lt;0.05). The results above indicated that Zhuanggu Jianxi Decoction could alleviate the synovial tissue inflammation in KOA patients by upregulating the mRNA and protein levels of LXRα and N-CoR in the LXRs/NF-κB pathway to downregulate the mRNA and protein levels of P50 and P65 and reduce the activity of the NF-κB pathway in the synovial tissue.