MMP-9 Concentrations Research Articles

Levels of metalloproteinases and adipose tissue hormones in men with coronary atherosclerosis

Aim. To study the effect of adipose tissue hormones on the level of metalloproteinases in men with verified coronary atherosclerosis and to assess associations between the studied biomarkers and abdominal obesity.Materials and methods. The study included 96 men aged 58.9 ± 5.1 years: 80 men with angiographically verified atherosclerosis and class II–III angina pectoris and 16 men without atherosclerosis. Anthropometric parameters were measured in all patients, and their blood was taken on an empty stomach. The blood levels of adiponectin, leptin, resistin, adipsin, amylin, and metalloproteinases (MMPs) -1, -2, -3, -7, -9, -10, -12, -13 were determined by the multiplex analysis. Statistical processing of the results was carried out using the SPSS 13.0 software.Results. In patients with severe atherosclerosis, lipocalin, MMP-1, MMP-7, and MMP-12 levels were higher than in the control group. The blood concentration of adiponectin in patients with atherosclerosis was reduced. Inverse correlations were revealed between waist circumference and concentrations of MMP-1 and MMP-12, as well as between body mass index and MMP-1. A moderate direct relationship was revealed between resistin and MMP-2 and MMP-3; between amylin and MMP-9; between adiponectin and MMP-12; between leptin and MMP-7.Conclusion. The results obtained suggest a relationship between the level of damage markers and adipose tissue hormones, which lead to complications of cardiovascular diseases and explain the effect of obesity on atherosclerotic plaque destabilization.

Potential of Plant-derived Exosome-like Nanoparticles from Physalis peruviana Fruit for Human Dermal Fibroblast Regeneration and Remodeling.

This research aimed to study the potential of PDEN from P. peruviana fruits (PENC) for regenerating and remodeling HDF. Large wounds are dangerous and require prompt and effective healing. Various efforts have been undertaken, but have been somewhat ineffective. Plant-derived exosome-like nanoparticles (PDEN) are easily sampled, relatively cost-effective, exhibit high yields, and are nonimmunogenic. The objective of the study was to isolate and characterize PDEN from Physalis peruviana (PENC), and determine PENC's internalization and toxicity on HDF cells, PENC's ability to regenerate HDF (proliferation and migration), and PENC ability's to remodel HDF (collagen I and MMP- 1 production). PENC was isolated using gradual filtration and centrifugation, followed by sedimentation using PEG6000. Characterization was done using a particle size analyzer, zeta potential analyzer, TEM, and BCA assay. Internalization was done using PKH67 staining. Toxicity and proliferation assays were conducted using MTT assay; meanwhile, migration assay was carried out by employing the scratch assay. Collagen I production was performed using immunocytochemistry and MMP-1 production was conducted using ELISA. MTT assay showed a PENC concentration of 2.5 until 500 μg/mL and being non-toxic to cells. PENC has been found to induce cell proliferation in 1, 3, 5, and 7 days. PENC at a concentration of 2.5, 5, and 7.5 μg/mL, also accelerated HDF migration using the scratch assay in two days. In remodeling, PENC upregulated collagen-1 expression from day 7 to 14 compared to control. MMP-1 declined from day 2 to 7 in every PENC concentration and increased on day 14. Meanwhile, ROS declined from day 2 to 7 and 14, with PENC inducing a rise in the ROS level compared to control. Overall, PENC at concentrations of 2.5, 5, and 7.5 μg/mL induced HDF proliferation and migration, upregulated collagen I production, and decreased MMP-1 levels. Isolated PENC was 190-220 nm in size, circular, covered with membrane, and its zeta potential was -6.7 mV; it could also be stored at 4°C for up to 2 weeks in aqua bidest. Protein concentration ranged between 170-1,395 μg/mL. Using PKH67, PENC could enter HDF within 6 hours. PENC was non-toxic up to a concentration of 500 μg/mL. Using MTT and scratch assay, PENC was found to elevate HDF proliferation and migration, and reorganize actin. Using immunocytochemistry, collagen I was upregulated by PENC, whereas MMP-1 concentration was reduced.

Characteristics of the synovial microenvironment and synovial mesenchymal stem cells with hip osteoarthritis of different bone morphologies

BackgroundVariations in bone morphology in patients with hip osteoarthritis (HOA) can be broadly categorized into three types: atrophic, normotrophic, and hypertrophic. Despite the investigations examining clinical elements, such as bone morphology, pain, and range of motion, our understanding of the pathogenesis of HOA remains limited. Previous studies have suggested that osteophytes typically originate at the interface of the joint cartilage, periosteum, and synovium, potentially implicating synovial mesenchymal stem cells (SMSCs) in the process. This study aimed to investigate the potential factors that drive the development of bone morphological features in HOA by investigating the characteristics of the synovium, differentiation potential of SMSCs, and composition of synovial fluid in different types of HOA.MethodsSynovial tissue and fluid were collected from 30 patients who underwent total hip arthroplasty (THA) with the variable bone morphology of HOA patients. RNA sequencing analysis and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were performed to analyse the genes in the normotrophic and hypertrophic synovial tissue. SMSCs were isolated and cultured from the normotrophic and hypertrophic synovial tissues of each hip joint in accordance with the variable bone morphology of HOA patients. Cell differentiation potential was compared using differentiation and colony-forming unit assays. Cytokine array was performed to analyse the protein expression in the synovial fluid.ResultsIn the RNA sequencing analysis, 103 differentially expressed genes (DEGs) were identified, predominantly related to the interleukin 17 (IL-17) signalling pathway. Using a protein–protein interaction (PPI) network, 20 hub genes were identified, including MYC, CXCL8, ATF3, NR4A1, ZC3H12A, NR4A2, FOSB, and FOSL1. Among these hub genes, four belonged to the AP-1 family. There were no significant differences in the tri-lineage differentiation potential and colony-forming capacity of SMSCs. However, RT-qPCR revealed elevated SOX9 expression levels in synovial tissues from the hypertrophic group. The cytokine array demonstrated significantly higher levels of CXCL8, MMP9, and VEGF in the synovial fluid of the hypertrophic group than in the normotrophic group, with CXCL8 and MMP9 being significantly expressed in the hypertrophic synovium.ConclusionUpregulation of AP-1 family genes in the synovium and increased concentrations of CXCL8, MMP9, and VEGF were detected in the synovial fluid of the hypertrophic group of HOA patients, potentially stimulating the differentiation of SMSCs towards the cartilage and thereby contributing to severe osteophyte formation.

DOES INFLAMMATORY AND METABOLOMIC ACTIVITY ON NORMAL AND OSTEOARTHRITIC CHONDROCYTES DIFFER BETWEEN MESENCHYMAL STEM CELLS (MSCS) DERIVED FROM THE INFRAPATELLAR FAT, SYNOVIUM, AND SUBCUTANEOUS TISSUES?

Osteoarthritis (OA) is a disabling disease depriving the quality of life of patients. Mesenchymal stem cells (MSCs) are recently used to modify the inflammatory and degenerative cascade of the disease. Source of MSCs could change the progression and symptoms of OA due to their different metabolomic activities. We asked whether MSCs derived from the infrapatellar fat (IPF), synovium (Sy) and subcutaneous (SC) tissues will decrease inflammatory and degenerative markers of normal and OA chondrocytes and improve regeneration in culture. Tissues were obtained from three male patients undergoing arthroscopic knee surgery due to sports injuries after ethical board approval. TNFa concentration decreased in all MSC groups (Sy=156,6±79, SC=42,1±6 and IPF=35,5±3 pg/ml; p=0,036) on day 14 in culture. On day seven (Sy=87,4±43,7, SC=23±8,9 and IPF=14,7±3,3 pg/ml, p=0,043) and 14 (Sy=29,1±11,2, SC=28,3±18,5 and IPF=20,3±16,2 pg/ml, p=0,043), MMP3 concentration decreased in all groups. COMP concentration changes however were not significant. Plot scores of tissues for PC2-13,4% were significantly different. Based on the results of liquid chromatography-mass spectrometry (LC-MS) metabolomics coupled with recent data processing strategies, clinically relevant seven metabolites (L-fructose, a-tocotrienol, coproporphyrin, nicotinamide, bilirubin, tauro-deoxycholic acid and galactose-sphingosine) were found statistically different (p<0.05 and fold change>1.5) ratios in tissue samples. Focusing on these metabolites as potential therapeutics could enhance MSC therapies.Acknowledgment: Hacettepe University, Scientific Research Projects Coordination Unit (#THD-2020-18692) and Turkish Society of Orthopedics and Traumatology (#TOTBID-89) funded this project. Feza Korkusuz MD is a member of the Turkish Academy of Sciences (TÜBA).

Regulation of MMP-2 by IL-8 in Vascular Endothelial Cells: Probable Mechanism for Endothelial Dysfunction in Women with Preeclampsia.

Endothelial dysfunction (ED) in preeclampsia (PE) results from the convergence of oxidative stress, inflammation, and alterations in extracellular matrix components, affecting vascular tone and permeability. The molecular network leading to ED includes IL-8 and MMP-2. In vitro, IL-8 regulates the concentration and activity of MMP-2 in the trophoblast; this interaction has not been studied in endothelial cells during PE. We isolated human umbilical vein endothelial cells (HUVECs) from women with healthy pregnancies (NP, n = 15) and PE (n = 15). We quantified the intracellular concentration of nitric oxide and reactive oxygen species with colorimetric assays, IL-8 with ELISA, and MMP-2 with zymography and using an ELISA-type system. An IL-8 inhibition assay was used to study the influence of this cytokine on MMP-2 concentration and activity. HUVECs from women with PE showed significantly higher oxidative stress than NP. IL-8 and MMP-2 were found to be significantly elevated in PE HUVECs compared to NP. Inhibition of IL-8 in HUVECs from women with PE significantly decreased the concentration of MMP-2. We demonstrate that IL-8 is involved in the mechanisms of MMP-2 expression in HUVECs from women with PE. Our findings provide new insights into the molecular mechanisms regulating the ED distinctive of PE.

Role of biomarkers of collagen metabolism and systemic inflammation in myocardial remodeling in patients with stable chronic coronary artery disease and obstructive sleep apnea

Aim. To study the relationship of biomarkers of collagen metabolism and systemic inflammation with left ventricular (LV) remodeling in patients with stable coronary artery disease (CAD) and obstructive sleep apnea (OSA).Material and methods. The study included 195 patients with stable CAD, of which 63 without OSA and 132 patients with combination of CAD and OSA. The mean age of patients was 63,4±3,7 years. Biomarkers of collagen metabolism and systemic inflammation were assessed by determining the concentration of matrix metalloproteinase (MMP)-9, tissue inhibitor of matrix metalloproteinase-1, monocyte chemoattractant protein-1 (MCP-1) and calculating the neutrophil-to-lymphocyte (NLR) and platelet-tolymphocyte ratio (PLR). Echocardiography was performed according to a standard protocol.Results. There were no significant differences in systemic inflammation parameters (MCP-1, NLR, PLR) between the group of patients with CAD and CAD with mild OSA and a significantly higher level of MCP-1, NLR, PLR in more severe OSA. In patients with CAD and severe OSA, the eccentric LV remodeling was diagnosed in 75% of individuals, while the concentric type was diagnosed in only 25%.Conclusion. In patients with stable CAD, the more severe the OSA, the more pronounced systemic inflammation (MCP-1, NLR, PLR), and there are higher proportion of eccentric LV hypertrophy, which may be associated with an imbalance of fibrosis markers (high concentration of MMP-9 with an almost unchanged level of tissue inhibitor of MMP-1).

Matrix metalloproteinases system profile analysis and their endogenous inhibitors in children with periodontal diseases and various dysplasia phenotypes

Relevance. The search and development of modern non-invasive methods for early periodontal disease detection are of scientific and practical value for a personalized approach to disease course prognosis and explaining the choice of treatment tactics. Morphological immaturity, high intensity of anabolic processes, functional failure of neurohumoral, endocrine and immunological defence systems combined with an imbalance between the synthesis and degradation of extracellular matrix components in children with undifferentiated connective tissue disease (UCTD) significantly increases the risk of developing periodontal diseases. The available data on the activity of salivary matrix metalloproteinases (MMPs), which play a leading role in regulating connective tissue protein metabolism and bone remodelling mechanisms in children with UCTD of various degrees, are scarce and require further study.Purpose. The study aimed to explain the clinical, diagnostic and prognostic value of MMPs as markers of inflammatory periodontal diseases in children with UC TD and dysplastic disorders of various se verity.Material and methods. The study included 67 children with UCTD (main group) and 34 children of health groups I and II (comparison group) aged 12-17. The UCTD severity was established according to the diagnostic criteria by L. N. Abbakumova (2006) and a scale for assessing the significance of phenotypic and visceral signs. The main group was divided into two subgroups: Subgroup 1 (n = 38) – children with mild and moderate UCTD; Subgroup 2 (n=29) – children with severe UCTD. The studied groups had their periodontal status assessed, as well as the concentration of MMP-1, MMP-2, MMP-8, MMP-9 and their tissue inhibitors (TIMP-1, TIMP-2) in the oral fluid identified using the enzyme immunoassay, along with calculation done for the MMP ⁄ TIMP coefficients that set a balance between the degradation and synthesis of collagen.Results. The children with phenotypic signs of UCTD in the oral fluid appeared to show a statistically significant increase in the MMP-1, MMP-2, MMP-8, and MMP-9 levels and an imbalanced ratio in MMP-1⁄TIMP-1, MMP- 2⁄TIMP-2, MMP-8⁄TIMP-1, MMP-9⁄TIMP-1, compared with health groups I, II. An increase in the MMP-1, MMP-2, and MMP-8 concentrations, along with dominating expression of MMP-9 over TIMP-1 in the oral fluid of children of Subgroup 2, causes an increase in intensity and prevalence of periodontal diseases compared to the patients in Sub-group 1 and comparison group.Conclusion. Thus, when children with UCTD don’t demonstrate an increase in specific tissue inhibitors TIMP-1 and TIMP-2 in their oral fluid, along with an increase in the levels of the respective matrixins is the key pathogenetic factor in the degradation of extracellular matrix proteins, which causes a depressing impact on the proliferative activity in the periodontal set of tissues.

The Impact of 45S5-Bioactive Glass on Synovial Cells in Knee Osteoarthritis-An In Vitro Study.

Synovial inflammation in osteoarthritis (OA) is characterized by the release of cartilage-degrading enzymes and inflammatory cytokines. 45S5-bioactive glass (45S5-BG) can modulate inflammation processes; however, its influence on OA-associated inflammation has hardly been investigated. In this study, the effects of 45S5-BG on the release of cartilage-degrading metalloproteinases and cytokines from synovial membrane cells (SM) isolated from patients with knee OA was assessed in vitro. SM were cultivated as SM monocultures in the presence or absence of 45S5-BG. On day 1 (d1) and d7 (d7), the concentrations of Matrix Metalloproteinases (MMPs) and cytokines were assessed. In 45S5-BG-treated SM cultures, MMP9 concentration was significantly reduced at d1 and d7, whilst MMP13 was significantly increased at d7. Concentrations of interleukin (IL)-1B and C-C motif chemokine ligand 2 (CCL2) in 45S5-BG-treated SM cultures were significantly increased at both time points, as were interferon gamma (IFNG) and IL-6 at d7. Our data show an effect of 45S5-BG on SM activity, which was not clearly protective, anti-inflammatory, or pro-inflammatory. The influence of 45S5-BG on MMP release was more suggestive of a cartilage protective effect, but 45S5-BG also increased the release of pro-inflammatory cytokines. Further studies are needed to analyze the effect of BGs on OA inflammation, including the anti-inflammatory modification of BG compositions.

Serum and Urinary Matrix Metalloproteinase-9 Concentrations in Dehydrated Horses.

Matrix metalloproteinase-9 is increased in renal tissue in human kidney disease, but its role as a biomarker for kidney disease has not been fully evaluated yet. The aim of this study was to evaluate serum MMP-9 (sMMP-9) and urinary MMP-9 (uMMP-9) concentrations in dehydrated horses. Dehydrated horses were prospectively included. Blood and urinary samples were taken at admission, and after 12, 24, and 48 h (t0, t12, t24, t48), an anti-equine MMP-9 sandwich ELISA was used. Four healthy horses served as the controls. Serum creatinine, urea, symmetric dimethylarginine (SDMA), urine-specific gravity, urinary protein concentration, fractional sodium excretion, and urinary gamma-glutamyl transferase/creatinine ratio (uGGT/Cr) were measured. Statistical analysis included a repeated measures ANOVA and mixed linear regression model. Overall, 40 dehydrated horses were included (mild dehydration 13/40, moderate 16/40, severe 11/40). Acute kidney injury was found in 1/40 horses; 7/40 horses showed elevated serum creatinine, 11/40 horses elevated serum SDMA, and 5/28 elevated uGGT/Cr at presentation. In dehydrated horses, sMMP-9 concentrations were significantly higher on t0 (median: 589 ng/mL, range: 172-3597 ng/mL) compared to t12 (340 ng/mL, 132-1213 ng/mL), t24 (308 ng/mL, 162-1048 ng/mL), and t48 (258 ng/mL, 130-744 ng/mL). In healthy horses, sMMP-9 (239 ng/mL, 142-508 ng/mL) showed no differences over time or compared to patients. uMMP-9 and uMMP-9/creatinine did not differ over time or to the controls. No differences were found between dehydration groups. Urinary casts (p = 0.001; estimate = 135) and uGGT/Cr (p = 0.03; estimate = 6.5) correlated with sMMP-9. Serum urea was associated with uMMP-9/Cr (p = 0.01, estimate 0.9). In conclusion, sMMP-9 was elevated at arrival in dehydrated patients compared to later measurements. Correlations to uGGT/Cr and urinary casts need further evaluation.

Sputum Biomarkers in Wood and Tobacco Smoke Etiotypes of Chronic Obstructive Pulmonary Disease.

There is a need to better understand the etiotypes of chronic obstructive pulmonary disease (COPD) beyond the tobacco-smoke (TS-COPD). Wood smoke COPD (WS-COPD) is characterized by greater airway compromise, milder emphysema, and slower rate of lung function decline than TS-COPD. However, it is unclear if these two etiotypes of COPD have differences in sputum biomarker concentrations. Objective was to compare sputum levels of selected sputum biomarkers between WS-COPD and TS-COPD, and healthy controls. Eighty-eight women (69±12 years) were recruited and classified into: WS-COPD (n=31), TS-COPD (n=29) and controls (n=28). Using ELISA, we determined induced sputum levels of metalloproteinase 9 (MMP-9), chemokine ligand 5 (CCL5), interleukin-8 (IL-8), chemokine ligand 16 (CCL16/HCC-4) and vascular endothelial growth factor (VEGF-1). Differences were analyzed by Kruskal-Wallis and Mann-Whitney-U tests and correlation between airflow limitation and biomarkers by Spearman's test. At similar degree of airflow obstruction, anthropometrics and medications use, the level of sputum CCL5 was higher in TS-COPD than WS-COPD (p=0.03) without differences in MMP-9, IL-8, CCL16/HCC-4, and VEGF-1. Women with WS-COPD and TS-COPD showed significantly higher sputum levels of MMP-9, IL-8 and CCL5 compared with controls (p<0.001). FEV1% predicted correlated negatively with levels of MMP-9 (rho:-0.26; P=0.016), CCL5 (rho:-0.37; P=0.001), IL-8 (rho:-0.42; P<0.001) and VEGF (rho:-0.22; P=0.04). While sputum concentrations of MMP-9, IL-8, and CCL5 were higher in COPD women compared with controls, women with TS-COPD had higher levels of CCL5 compared with those with WS-COPD. Whether this finding relates to differences in pathobiological pathways remains to be determined.

Neuropeptide Y, a potential marker for lupus, promotes lupus development

ObjectiveRelationship between neuropeptide Y (NPY) serum levels, NPY genetic mutation with systemic lupus erythematosus (SLE) pathogenesis is yet to be clarified, and role of NPY in development of SLE needs elucidation. MethodThis study included 460 SLE patients, 472 non-SLE cases, 500 healthy volunteers. Serum NPY, matrix metalloproteinase-1 (MMP-1) and MMP-8 levels were tested by ELISA. Genotyping 7 NPY single nucleotides polymorphisms (SNPs) (rs5573, rs5574, rs16129, rs16138, rs16140, rs16147, rs16478) was obtained by Kompetitive Allele-Specific PCR (KASP) method. Pristane-induced lupus mice were treated with NPY-Y1 receptor antagonist, and histological analysis, serological changes of the mice were evaluated. ResultsNPY serum concentrations were significantly increased in SLE patients when compared to that in healthy volunteers, non-SLE cases. Rs5573 G allele, rs16129 T allele, rs16147 G allele frequencies were significantly different between SLE cases and healthy controls. Rs5574 TT + TC genotypes were related to levels of IgG, C3, C4 and erythrocyte sedimentation rate, and rs16138 GG + GC genotypes correlated with SLE cases with anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA) (+). Serum MMP-1, MMP-8 concentrations were higher in SLE patients, and NPY levels were significantly related to MMP-1, MMP-8 levels. After treatment of lupus mice with NPY-Y1 receptor antagonist, damage of liver, spleen and kidney was alleviated, production of autoantibodies (anti-nuclear antibody (ANA), total IgG, anti-dsDNA) and MMP-1, MMP-8 was down-regulated, and differentiation of CD3+, CD8+ T cells, B cells, monocytes, macrophages, T helper 1 (Th1), Th2, Th17 cells was reversed. ConclusionNPY may be a biomarker for lupus, which may promote occurrence and development of lupus.

Higher Content but No Specific Activity in Gelatinase B (MMP-9) Compared with Gelatinase A (MMP-2) in Human Renal Carcinoma.

Gelatinases belong to a group of enzymes known as matrix metalloproteinases (MMPs). Gelatinases A and B (MMP-2 and MMP-9, respectively) are the enzymes with the highest ability to destroy collagen, primarily type IV collagen, which is an essential component of the base membrane. Hence, it can be assumed that they are involved, among other things, with the metastasis process of cancer. As a result, the objective of this study was to assess the presence, activity, and expression of selected gelatinases in human renal cancer. Healthy (n = 20) and clear-cell kidney cancer tissue samples (G2 n = 10, G3 n = 10) were analyzed. The presence and content of MMPs were measured using the Western blot and ELISA methods, respectively. The activity (actual and specific) was analyzed with a fluorimetric method. The presence of both investigated enzymes was demonstrated in the representative zymogram. MMP-9 showed the most intensive saturation. It has been observed that both gelatinases occur primarily in high molecular complexes in the human kidney, regardless of whether it is a control or tumor tissue. Both gelatinases were present in comparable amounts in healthy tissues of the kidney. MMP-9 showed a higher content than MMP-2 in both renal cancer grades, but we observed the enhanced activity of both gelatinases with an increase in the grade of renal cancer. A higher MMP-9 content and, on the other hand, lower specific activity in the cancer tissue suggest that MMP-9 is predominantly present in an inactive form in renal cancer. The higher activity of MMP-9 demonstrated using the zymography method may be a cause of different values of activity that depend on the phase of the carcinogenic process. The present study revealed changes in the tested gelatinases in healthy and cancerous tissues of renal cell carcinoma. Therefore, it can be concluded that matrix metalloproteinases 2 and 9 are enzymes directly involved in carcinogenesis, and hence, it seems that MMPs may have potential in the diagnosis and treatment of renal carcinoma.

In-Vitro and In-Silico Approach Distinguish ER-α and HER-2 Antagonistic Properties of Indian Herbal Formulation on Breast Cancer

Objectives: The anticancer effect of an Indian herbal preparation was studied under a cancer cell line, as well as the in silico computational methods that explain the probability of protein ligands binding to ER- α and HER-2 receptors.&#x0D; Method: The in vitro anticancer activity of Body Revival® suspension (BR) was determined using cytotoxicity tests, cell invasion and migration assays, and metastatic protein expression assays using MCF-7 breast cancer cells. The computational predictive biological method was applied to find out the pharmacodynamic and pharmacokinetic interactions between the active molecules present in the BR and ER- α/and HER-2 of breast cancer.&#x0D; Results: BR showed significant and dose dependent cytotoxic effects on MCF-7 cells. The 50% effective cytotoxic dose of BR was 34.27µl/ml. It restricted invasion (26%) and migration (28%) of cancer cells than BSA control. MMP-9 and IL-6 concentration were reduced significantly (p&lt;0.001) after treatment. Cucurbitacin B had maximum in silico binding energy score (-7.8) with ER-α, while symconoside B had with HER-2 (-8.4); but, among the other interactions between the two ligands and receptors, withaferin A had the highest affinity (-15.3). Additionally, withaferin A, symconoside A, and symconoside B curcurbitacin A demonstrated bioavailability and fulfilled safety standards. &#x0D; Conclusion: Body Revival® showed as a powerful multi-target inhibitor of ER- α and HER-2 that has prospective anticancer action without side effects, and may be useful in the therapy management following a successful trial in breast cancer patients.&#x0D; Keywords: Breast cancer, Cytotoxicity, MCF-7, ER- α, HER-2, Herbs, In Silico

Prognostic value of humoral markers in patients with anthracycline-related cardiac dysfunction

Aim. To carry out a 12-month study on the prognostic role of humoral markers responsible for the main mechanisms of initiation of cardiotoxic myocardial damage (endothelin-1, soluble Fas-L, N-terminal pro-brain natriuretic peptide (NT-proBNP), tumor necrosis factor-α, interleukin (IL)-1β, matrix metalloproteinase (MMP)-2 and MMP9, soluble form of the ST2 protein (sST2), a tissue inhibitor of metalloproteinase-1, and tetranectin) in assessing the risk of progression of anthracycline-related left ventricular dysfunction.Materials and methods. The study included a total of 114 women aged 48.0 (46.0; 52.0) years without concomitant cardiovascular diseases and risk factors who received chemotherapy with anthracyclines in the past. The levels of serum biomarkers were determined using the enzyme immunoassay. Transthoracic echocardiography was performed at baseline and at 12 months of follow-up.Results. After 12 months of follow-up, all patients were retrospectively divided into 2 groups: group 1 (n = 54) included patients with an unfavorable course of anthracycline-related cardiac dysfunction (ARCD), group 2 (n = 60) encompassed patients with a favorable course of the disease. According to the ROC analysis, MMP-2 ≥ ≥ 338.8 pg / ml (sensitivity 57%, specificity 78%; AUC = 0.629; p = 0.025), MMP-9 ≥ 22.18 pg / ml (sensitivity 89%, specificity 87%; AUC = 0.886; p &lt; 0.001), sST2 ≥ 32.4 ng / ml (sensitivity 64%, specificity 70.5%; AUC = 0.691; p = 0.002), and tetranectin ≤ 15.4 pg / ml (sensitivity 69%, specificity 72%; AUC = 0.764; p &lt; 0.001) were identified as predictors of an adverse course of ARCD. When comparing ROC curves, it was found that the concentration of MMP-9 (p = 0.002) was the most significant predictor of the progression of ARCD.Conclusion. MMP-2 and -9, soluble ST2, and tetranectin can be considered as non-invasive markers for assessing the risk of ARCD progression. At the same time, an increased level of MMP-9 is the most significant predictor of ARCD progression.

The effects of statin therapy on aneurysm size, growth rate, and matrix metalloproteinases-9 levels in patients with aortic aneurysm: a systematic review and meta-analysis

BackgroundAortic aneurysm enlargement over time causes rupture, which frequently results in death. The family of proteases known as matrix metalloproteinases (MMP) is assumed to be proteolytic activity involved in the growth of aortic aneurysms. Statins are pleiotropic lipid-lowering medications with anti-inflammatory action. Statins can lower aneurysmal enlargement and MMP secretion, according to a number of studies, however the evidence is still up for debate. The purpose of this study is to assess how statins affect aortic aneurysm patient's aneurysm diameter size, growth rate, and MMP-9 levels.MethodsFrom January 2000 to December 2022, electronic journal searches in PubMed, ScienceDirect, and Cochrane were conducted to discover papers evaluating the effects of statin treatment in patients with aortic aneurysm. Aneurysm diameter size, growth rate, and MMP-9 levels were the outcomes we were looking for. Meta-analyses were run on the included studies, and mean differences (MD) and 95% CIs were calculated with Review Manager v5.4.ResultsOur analysis includes a total of ten research. Statin medication substantially reduced aneurysm diameter size by 0.30 mm (P = 0.04; MD − 0.30; 95% CI − 0.58 to − 0.01) and growth rate by 0.34 mm/year (P < 0.00001; MD − 0.34; 95% CI − 0.40 to − 0.29) compared to placebo. There was no significant change in MMP-9 concentrations between individuals with aortic aneurysm who took a statin and those who did not.ConclusionOverall, this meta-analysis demonstrates that statin medication is considerably helpful in reducing aneurysm diameter size and aneurysmal growth rate in individuals with aortic aneurysm.

The Complementary Effects of Dabigatran Etexilate and Exercise Training on the Development and Stability of the Atherosclerotic Lesions in Diabetic ApoE Knockout Mice.

Aim: To determine the complementary effects of dabigatran etexilate (DE), exercise training (ET), and combination (DE + ET) on the development and stability of the atherosclerotic lesions in diabetic apoE knockout (apoE-/-) mice. Methods: In 48 male apoE-/- diabetic mice, streptozotocin (STZ) was induced for 5 consecutive days. Mice received a high-fat diet (HFD) for 8 weeks and then were randomized into four groups (1. Control/CG, 2. DEG: HFD with DE, 3. ETG: ET on treadmill, 4. DE + ETG: combination DE and ET treatment). At the end of the eighth week, all mice were euthanatized and morphometry of the aortic lesions at the level of aortic valve was obtained. Collagen, elastin, MCP-1, TNF-a, matrix metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations within plaques at the aortic valve were determined. Results: All active groups had significantly smaller aorta stenosis (DEG:7.9 ± 2.2%, ETG:17.3 ± 5.3%, DE + ETG:7.1 ± 2.7%) compared to CG (23.3 ± 5.5% p < 0.05), reduced the relative intra-plaque content of MCP-1, macrophages, MMP-3, and MMP-9, and considerably increased collagen, elastin, and TIMP-1 (p < 0.05). Group 4 showed the most pronounced results (p < 0.05). Both DEG and DE + ETG significantly reduced MMP-2 and TNF-a concentrations compared to ETG and CG (p < 0.010). Conclusion: DE and ET treatment of diabetic apoE-/- mice resulted in complementary amelioration of atherosclerotic lesions development and stability, mediated by the anti-inflammatory modulation of both DE and ET.

Immune Profiling of Secreted Factors from Human Vestibular Schwannoma Cells and Tumor-associated Macrophages.

This study compared the immune-related secretory capacity of human vestibular schwannoma (VS) and tumor-assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte-derived macrophages [Mo-MFs], respectively), and examined relationships with presurgical hearing and tumor size. VS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B+ ) and TAMs (CD68+ ) were isolated from VS tissue for culture. The secreted levels of 65 immune-related factors were measured and compared using unpaired t-tests with Welch correction (schwannoma vs. SCs) or Mann-Whitney tests (TAMs and Mo-MFs). Associations between factor concentration and word recognition (WR), pure-tone average (PTA), and tumor size were evaluated with Spearman correlation. Secreted factors with significantly higher concentrations in schwannoma versus SC supernatants included IL-2 and BAFF, whereas MMP-1, IL-6, FGF-2, VEGF-A, MIP-3α, and GRO-α concentrations were significantly higher in TAMs versus Mo-MFs (all p < 0.05). Worse WR was significantly associated with higher secretion of fractalkine, eotaxin-3, CD30, and IL-16 by VS cells; IP-10, eotaxin-3, multiple interleukins, GM-CSF, SCF, and CD30 by TAMs; and TNF-α and MIP-1α by Mo-MFs (all p < 0.05). Worse PTA was significantly correlated with higher secretion of IL-16 by VS cells (p < 0.05). Larger tumor size was significantly correlated with higher secretion of eotaxin by VS cells, and of IL-7, IL-21, and LIF by TAMs (all p = 0.017). Differential secretion of immune-related factors was observed in schwannoma versus normal SCs and in TAMs versus Mo-MFs, some of which were correlated with worse hearing and larger VS tumors. N/A Laryngoscope, 134:S1-S14, 2024.

Assessment of connective tissue metabolism in patients with head and neck malignancies treated with radiotherapy.

&lt;br&gt;&lt;b&gt;Introduction:&lt;/b&gt; Despite the use of highly specialized irradiation techniques in the treatment of head and neck tumors, it is still impossible to selectively destroy cancer cells without damaging normal structures, including connective tissue cells.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The aim of the study was to analyze the concentration of degradation markers such as collagen type I (carboxyterminal telopeptide of type I collagen; ICTP) and elastin (elastin-derived peptides; EDPs) as well as selected metalloproteinases (MMP-1, MMP-2, MMP-9) in patients with head and neck malignancies undergoing radiotherapy.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Material and methods:&lt;/b&gt; The test group consisted of 56 men, who underwent radical or palliative radiotherapy. The concentrations of ICTP, EDPs, MMP-1, MMP-2, MMP-9 were determined in three blood samples collected from patients prior to radiotherapy, immediately after its completion and 3 months after the therapy.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Results&lt;/b&gt;: Both radical and palliative radiotherapy contribute to a significant increase in the concentration of EDPs. At the time of healing of post-irradiation lesions, the level of EDPs was reduced in both groups. The ICTP concentration was not affected by radiotherapy. No significant differences were observed in the concentration of MMP-1 and MMP-2 before and after radiotherapy. Radical radiotherapy caused a statistically significant late reduction in the concentration of MMP-9. The lowest concentrations of MMP-1, MMP-2, MMP-9 in the serum of patients qualified for palliative radiotherapy were recorded in a samples collected three months post-irradiation.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The degradation markers of key extracellular matrix structural proteins may be helpful tools in the objective assessment of radiation-induced injuries to the connective tissue.&lt;/br&gt.

Cavin1 activates the Wnt/β-catenin pathway to influence the proliferation and migration of hepatocellular carcinoma

Introduction and ObjectivesCavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression. Materials and MethodsCavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis. ResultsCavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished β-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression. ConclusionsCavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/β-catenin axis activation.

Metalloproteinase-2 in failed back surgery syndrome caused by epidural fibrosis: can it play a role in persistent pain?

Failed Back Surgery Syndrome (FBSS) occurs in 10-40% of patients treated surgically due to disk herniation (DH). There are several factors that can cause a predisposition to FBSS, but the exact pathomechanism has not been elucidated. The aim of this study was to investigate Metalloproteinase-2 (MMP-2) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) activities in a homogeneous group of FBSS patients with epidural fibrosis in comparison to its activity in patients with surgically treated DH. DH, FBSS, and control (CG) groups consisted of 30 subjects. The patients were assessed clinically by the Numerical Rating Scale (NRS), McGill Pain Questionnaire (SF -MPQ), Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). Serum concentrations of MMP-2 and TIMP-2 were measured by using the immunoenzymatic method. There was a significantly higher MMP-2 expression (medians: 4797.49 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 166.40 vs. 109.60; p < 0.0001) in the DH compared to the CG. Significantly higher MMP-2 expression (4219.95 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 150.17 vs. 109.60; p = 0.0003) were also found in the FBSS compared to the CG. The activity of MMP-2, measured as MMP-2/TIMP-2, did not significantly change between the DH, FBSS, and CG. MMP2 expression (p < 0.0001) and TIMP-2 concentration (p < 0.0001) were significantly higher in the DH than FBSS. Results indicate the presence of a contribution of MMP-2 and TIMP-2 in DH and FBSS. Unchanged activity of MMP-2 can indicate an insufficiency in the MMP-2 repair system in both diseases. Lower MMP-2 expression and TIMP-2 concentration in the FBSS group can reflect the chronicity of the process.