Inhibition of complement system-related gene ITGB2 attenuates epithelial–mesenchymal transition and inflammation in diabetic nephropathy

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: Feb. 8, 2025

Emerging evidences have indicated a role of the complement system in pathogenesis diabetic nephropathy (DN). Thus, this study was conducted to explore system-related key biomarkers for patients with DN. DN microarray datasets were downloaded from GEO database, followed by differentially expressed genes (DEGs) screening. Complement (CSRGs) searched various databases. Weighted Gene Co-expression Network Analysis (WGCNA) employed screen DN-related genes, then differential CSRGs (DCSRGs) identified, protein–protein interaction (PPI) network construction. In addition, acquired two machine learning algorithms, immune infiltration analysis, Set Enrichment (GSEA), and potential drugs screening conducted. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) western blotting utilized detect ITGB2 expression. Then cell viability, inflammatory factors, expression epithelial–mesenchymal transition (EMT) fibrosis markers determined using Cell Counting Kit-8 (CCK-8) assay, enzyme linked immunosorbent assay (ELISA), assays, respectively. total, 1012 DEGs 974 screened, intersection analysis three (DN-related CSRGs) yielded 13 which considered as DCSRGs. Subsequently, 2 identified learning, namely VWF ITGB2. The both enriched pathways chemokine signaling pathway, CAMs, focal adhesion natural killer cell-mediated cytotoxicity, significantly correlated activated mast cells, resting NK macrophages. Also, related clinical features, including age, serum creatinine level, GFR (MDRD). Besides, mRNA protein levels HG-treated HK-2 cells remarkably elevated. Moreover, viability TNF-α, IL-6, IL-12, α-SMA, E-cadherin vimentin changed HG administration reversed ITGB2-silence. gene overexpressed DN, inhibition attenuated EMT inflammation

Language: Английский

Identification of Factors Associated with Mortality in the Elderly Population with SARS-CoV-2 Infection: Results from a Longitudinal Observational Study from Romania

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 202 - 202

Published: Feb. 3, 2024

The progression of SARS-CoV-2 infection has been linked to a hospitalization rate 20%. susceptibility increases with age, resulting in severe and atypical clinical forms the disease. severity elderly population can be attributed several factors, including overexpression angiotensin-converting enzyme 2 (ACE2) receptors, immunosenescence, alterations intestinal microbiota that facilitate cytokine storm. In light these observations, we conducted retrospective analysis based on prospectively collected data between 23 December 2021 30 April 2022 (the fourth wave infection). We analyzed patients aged over 60 years who were hospitalized county hospital Romania. primary objective our study was assess risk factors for an unfavorable outcome, while secondary baseline characteristics enrolled patients. included 287 cases complete electronic medical record from this available cohort aimed retrospectively evaluate group 127 progressed, unfortunately, toward outcome versus 160 favorable outcome. used Combined Ordinal Scale Severity combines WHO ordinal scale degrees inflammation at time initial assessment. age 70 79 had highest percentage, accounting 48.0%—61 patients, deceased noted statistically significant differences groups related other cardiovascular diseases, nutritional status, hematological neurological/mental or digestive disorders, comorbidities. Regarding status there all BMI > kg/m2, p = 0.004. presence associated Our results indicate cough, 80 years, ≤ 0.049. terms dyspnea it 0.001. study, laboratory test level across various categories, focusing determined by average values specific biomarkers. findings show that, exception IL-6, biomarkers tend rise progressively Moreover, are significantly higher experiencing adverse outcomes. among categories highly (p-values < 0.001). CART algorithm revealed cut-off point 4 stand out as important reference value high developing critical COVID-19. death proinflammatory hormonal changes, vitamin D deficiencies, comorbidities, pictures.

Language: Английский

Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 25, 2024

Unlocking the potential of broadly reactive coronavirus monoclonal antibodies (mAbs) and their derivatives offers a transformative therapeutic avenue against severe COVID-19, especially crucial for safeguarding high-risk populations. Novel mAb-based immunotherapies may help address reduced efficacy current vaccines neutralizing mAbs caused by emergence variants concern (VOCs). Using phage display technology, we discovered pan-SARS-CoV-2 mAb (C10) that targets conserved region within receptor-binding domain (RBD) virus. Noteworthy, C10 demonstrates exceptional in recognizing all assessed VOCs, including recent Omicron variants. While lacks direct neutralization capacity, it efficiently binds to infected lung epithelial cells induces lysis via natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Building upon this mAb, engineered C10-based, Chimeric Antigen Receptor (CAR)-T endowed with efficient killing capacity SARS-CoV-2-infected cells. Notably, NK CAR-T-cell mediated effectively reduces viral titers. These findings highlight non-neutralizing providing immune protection emerging infectious diseases. Our work reveals effective targeting proof-of-concept application CAR-T cell therapy combating SARS-CoV-2 infections. Furthermore, holds promise development innovative antibody-based cell-based strategies COVID-19 expanding array options available populations.Trial registration: ClinicalTrials.gov identifier: NCT04093596.

Language: Английский