Plasma Levels of MMPs and TIMP-1 in Patients with Osteoarthritis After Recovery from COVID-19.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPS) play a key role in the pathogenesis of osteoarthritis (OA). Recent research showed the involvement of some MMPs in COVID-19, but the results are limited and contradictory. OBJECTIVE: In this study, we investigated the levels of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10) and TIMP-1 in the plasma of patients with OA after recovery from COVID- 19. METHODS: The experiment involved patients aged 39 to 80 diagnosed with knee OA. All study participants were divided into three research groups: the control group included healthy individuals, the group OA included patients with enrolled cases of OA, and the third group of OA and COVID-19 included patients with OA who recovered from COVID-19 6-9 months ago. The levels of MMPs and TIMP-1 were measured in plasma by enzyme-linked immunosorbent assay. RESULTS: The study showed a change in the levels of MMPs in patients with OA who had COVID- 19 and those who did not have a history of SARS-CoV-2 infection. Particularly, patients with OA who were infected with coronavirus established an increase in MMP-2, MMP-3, MMP-8, and MMP-9, compared to healthy controls. Compared to normal subjects, a significant decrease in MMP-10 and TIMP-1 was established in both groups of patients with OA and convalescent COVID-19. CONCLUSION: Thus, the results suggest that COVID-19 can affect the proteolysis-antiproteolysis system even after a long postinfectious state and may cause complications of existing musculoskeletal pathologies.

An evaluation of matrix metalloproteinase-9 (Mmp-9) and tissue inhibitor metalloprotein-ase-1 (Timp-1) Serum levels and the Mmp-9/Timp-1 Ratio in Covid-19 patients

Background: The progression of COVID-19 has different clinical presentations, which raises a number of immunological questions. Objective(s): This study aimed to investigate MMP-9 and TIMP-1 levels in patients diagnosed with COVID-19 and whether the MMP-9/TIMP-1 ratio is associated with lung involvement in COVID-19. Method(s): This study was conducted with 192 patients and 45 healthy controls. ELISA was used to measure the MMP-9 and TIMP-1. Result(s): The MMP-9 and TIMP-1 levels of the patients were found to be higher than those of the controls. MMP-9 and TIMP-1 were detected more in patients with lung involvement on chest CT scans than in those with no lung involvement on chest CT scans. A comparison of lung involvement levels revealed no difference was found between the groups. The MMP-9/TIMP-1 ratio was 5.8 in the group with lung involvement on chest CT scans and 6.1 in the group without lung involvement on chest CT scans. No difference was found between the two groups. A comparison with respect to lung involvement levels showed that the MMP-9/TIMP-1 ratio difference was found between the groups. Conclusion(s): Diagnostic and treatment methods targeting MMP-9 activity or neutrophil activation may be important in predict-ing lung involvement in COVID-19 and directing clinical outcomes.Copyright © 2023 Demir NA et al. Licensee African Health Sciences.

Application of weighted gene co-expression network and immune infiltration for explorations of key genes in the brain of elderly COVID-19 patients.

Introduction: Although many studies have demonstrated the existing neurological symptoms in COVID-19 patients, the mechanisms are not clear until now. This study aimed to figure out the critical molecular and immune infiltration situations in the brain of elderly COVID-19 patients. Methods: GSE188847 was used for the differential analysis, WGCNA, and immune infiltration analysis. We also performed GO, KEGG, GSEA, and GSVA for the enrich analysis. Results: 266 DEGs, obtained from the brain samples of COVID-19 and non-COVID-19 patients whose ages were over 70 years old, were identified. GO and KEGG analysis revealed the enrichment in synapse and neuroactive ligand-receptor interaction in COVID-19 patients. Further analysis found that asthma and immune system signal pathways were significant changes based on GSEA and GSVA. Immune infiltration analysis demonstrated the imbalance of CD8+ T cells, neutrophils, and HLA. The MEpurple module genes were the most significantly different relative to COVID-19. Finally, RPS29, S100A10, and TIMP1 were the critical genes attributed to the progress of brain damage. Conclusion: RPS29, S100A10, and TIMP1 were the critical genes in the brain pathology of COVID-19 in elderly patients. Our research has revealed a new mechanism and a potential therapeutic target.

Investigation of the relationship between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 with SARS CoV-2 infections

SARS-CoV-2 stands for severe acute respiratory syndrome coronavirus 2. Matrix metalloproteinases-9 (MMP-9) performs a crucial physiological role. In addition to its roleICLEin the molecular basis of lung fibrosis, this enzyme may also play a part in the "cytokine storm," which may represent one of the potential scenarios during coronavirus infection. Tissue inhibitors of metalloproteinase (TIMPs) are well-known for their ability to regulate MMP activity during remodeling of the extracellular matrix. As cytokines, they are also thought of as signaling molecules that impact on a wide range of biological processes. This study aimed to investigate the link between each of MMP-9 and TIMP-1, and COVID19 disease. A total of 58 COVID-19 patients and 30 apparently healthy adults enrolled in this study. The ORF1ab, E and N genes of SARS-CoV-2 were detected using multiplex real-time PCR, while the ELISA technique was used to estimate the level of serum MMP-9, TIMP-1, and C-reactive protein (CRP). The study results demonstrated higher concentrations of MMP-9 in COVID-19 patients (2810 ± 1160 pg/ml) compared to controls (2110 ± 850 pg/ml), with non-significant differences (p=0.002). Unlike, TIMP-1, showed considerably higher levels in the patient's group (541.53 ± 201.42 pg/ml) than in controls (276.33 ± 67.26 pg/ml) with high significant differences (p ≤ 0.001). Considering this study, TIMP-1 in COVID patients most likely play an important role in inflammatory response. Its clinical utility as a biomarker may be insufficient, but it provides a useful data in the diagnosis of COVID‐19. © 2023, Bangladesh Society for Microbiology, Immunology and Advanced Biotechnology. All rights reserved.

Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status.

Background: Systemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients. Methods: Ninety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support. Results: Serum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score <5 [PIIINP: 7.2 (5.4-9.5) vs. 7.1 (4.5-9.9), p = 0.782; TIMP-1: 298.1 (20.5-460) vs. 222.2 (28.5-452.8), p = 0.01; HA: 117.1 (55.4-193.7) vs. 75.1 (36.9-141.8), p = 0.258]. TIMP-1 showed moderate correlation with CRP (r = 0.312, p = 0.003) and with LDH (r = 0.263, p = 0.009). CRP and serum LDH levels were significantly higher in COVID-19 patients with WHO score ≥5 compared to the group of patients with WHO score < 5 [15.8 (9-44.5) vs. 9.3 (3.4-33.8), p = 0.039 and 373 (282-465) vs. 289 (218-383), p = 0.013, respectively]. Conclusion: In patients with COVID-19, circulating TIMP-1 was associated with disease severity and with systemic inflammatory index, suggesting that TIMP-1 could represent a promising non-invasive prognostic biomarker in COVID-19 patients. Interestingly, our results prompted that serum TIMP-1 level may potentially be used to select the patients for therapeutic approaches targeting matrix metalloproteases pathway.

Estimation of serum levels of vitamin D, calcium, phosphorous, matrix metalloproteinases 1, 2 and tissue inhibitor matrix metalloproteinase -1 in patients with acrofacial vitiligo during COVID-19

Vitiligo is the loss of functional melanocytes from epidermis. Acrofacial type occurs when depigmentation affects parts apart from the body centers as face, head, hands and feet. Vitamin D may have a role in both acrofacial vitiligo and Covid 19. The present study designed to investigate the role of serum levels of vitamin D, Calcium (Ca), phosphorous (Ph), matrix metalloproteinases 1 and 2 (MMPs 1, 2) and tissue inhibitor matrix metalloproteinase -1 (TIMP1) in acrofacial vitiligo during Covid-19. Activity of MMP1, MMP2 and TIMP1 calcium and phosphorous levels were measured in serum. 40 control subjects and 40 patients’ suffering acrofacial vitiligo, whose ages ranged from 17-36 years with matching sex and skin phototype all were examined. Vitamin D and Ca levels showed significant decline in their levels in acrofacial vitiligo patients when compared to controls. Additionally, TIMP1 and MMP2 levels displayed significant decrease compared to control subjects, while elevation in MMP1 level was recognized. However, Phosphorous showed no significant difference between controls and cases. No significant alteration between patients and control in terms of sex & age was detected in the present study. We concluded that the selected measured parameters were suggested to participate in controlling and regulating the processes of melanocyte activity and migration in acrofacial vitiligo. These parameters were correlated to each other, since significant reduction in vitamin D & Ca was associated with the decrease in MMP2 and TIMP1 as well as significant increase in MMP1 in vitiligo patients. However, no significant differences were noticed in phosphorous levels in acrofacial vitiligo when compared to control subjects. Significant reduction in vitamin D was also correlated to Covid-19. ©2022 National Information and Documentation Center