Biology subjects

Hmadcha, A.

Publications and source records attributed to Hmadcha, A..

3 recordsLinked to original sources

bioRxiv2026

miR-18a-5p upregulates Orai1 expression to promote vascular smooth muscle cell proliferation and neointimal hyperplasia after injury.

RationaleNeointimal hyperplasia, a key contributor to restenosis, is driven by the abnormal proliferation and migration of vascular smooth muscle cells (VSMC), although the underlying molecular mechanisms remain incompletely understood. This study aimed to characterize the structural, transcriptomic, and post-transcriptional changes driving neointima formation, with a focus on store-operated calcium entry (SOCE) pathways and microRNA (miRNA) regulation. MethodsA rat carotid angioplasty model was employed to assess neointimal development at 1, 2, and 3 weeks post-injury. VSMC isolated from rat coronary arteries and A7r5 VSMC line were used to assess intracellular Ca2+ dynamics, and expression of gene and protein. ResultsProgressive neointimal thickening and impaired contractility were observed after carotid artery injury, accompanied by significant VSMC proliferation. Transcriptomic profiling revealed differentially expressed genes (DEGs) at 1 and 3 weeks, with enrichment in pathways related to cell cycle, migration, and Ca2+ signaling. Among Ca2+ -regulatory genes, Orai1 and SARAF were upregulated in the neointima and shown to colocalize and interact post-injury. Functional studies in VSMC demonstrated that Orai1, but not SARAF, is involved in insulin-like growth factor 1 (IGF-1)-induced proliferation and SOCE activation. Moreover, miRNA profiling identified miR-18a-5p, from the miR-17-92 cluster, as the most upregulated miRNA early post-injury. miR-18a-5p unusually enhanced Orai1 promoter activity and protein expression, leading to increased SOCE in VSMC. In human coronary arteries from ischemic hearts Orai1 was upregulated, suggesting the potential translational relevance of Orai1 in vascular pathology. ConclusionsOur findings identify miR-18a-5p as a novel positive regulator of Orai1 and SOCE activity in VSMC. The results uncover a miRNA/SOCE regulatory circuit that orchestrates Ca2+ -dependent VSMC signaling during vascular remodeling and may serve as a potential therapeutic target pathway in occlusive vascular disease.

physiology↗

bioRxiv2025

Discovery of a novel antibiotic class targeting the enolase of Acinetobacterbaumannii

High-throughput screening studies provide an additional approach to discovering repurposed drugs for antimicrobial treatments. In this work, we report the identification of ENOblock, an anticancer drug, as a novel antibiotic class. We computationally and experimentally validated that ENOblock synergizes with colistin, the last resort antibiotic, the colistin. Additionally, we identified enolase as the potential bacterial target for ENOblock. The in silico and in vitro antibacterial activity of ENOblock translated into potent in vivo efficacy in animal infection model. Collectively, the preclinical data support the selection of ENOblock as a promising candidate for antimicrobial development, with the potential to address the urgent threat of infections caused by Acinetobacter baumannii.

microbiology↗

bioRxiv2024

Antibacterial activity of tamoxifen derivatives against methicillin-resistant Staphylococcus aureus

The present work aimed to discover new tamoxifen derivatives with antimicrobial potential, particularly targeting methicillin-resistant Staphylococcus aureus (MRSA). The MIC of 22 tamoxifen derivatives was determined against S. aureus reference and MRSA strains, using microdilution assays. The antibacterial effects of selected tamoxifen derivatives against MRSA (USA7) were assessed through bacterial growth assays. Bacterial membrane permeability and molecular docking assays were performed. The MIC of the tamoxifen derivatives against MRSA ranged from to 16 to >64 g/mL. Bacterial growth assays demonstrated that tamoxifen derivatives 2, 5, and 6 reduced dose-dependently the growth of the USA7 strain. Moreover, treatment of MRSA with derivatives 2 and 5 resulted in increased membrane permeabilization without being the cell wall their molecular target. These data suggest that tamoxifen derivatives exhibit antibacterial activity against MRSA, potentially broadening the spectrum of available drug treatments for combating antimicrobial-resistant Gram-positive bacteria. ImportanceThe development of new antimicrobial therapeutic strategies requires immediate attention to avoid the tens of millions of deaths predicted to occur by 2050 as a result of multidrug-resistant (MDR) bacterial infections. In this study, we assessed the antibacterial activity of 22 tamoxifen derivatives against methicillin-resistant Staphylococcus aureus (MRSA). We found that three tamoxifen derivatives exhibited antibacterial activity against MRSA clinical isolats, presenting MIC50 values between 16 and 64 g/mL and reducing bacterial growth over 24 h. Additionally, this antibacterial activity for two of the derivatives was accompanied by increased membrane permeability of MRSA. Our results suggest that tamoxifen derivatives might be used as a potential therapeutic alternative for treating MRSA strains in an animal model of infection.

microbiology↗