Mashhad Razavi Hospital Razavi Journal of Medicine 3115-753X 14 4 2026 10 01 Molecular Effects of Curcumin Nanomicelles on Wharton's Jelly-Derived Mesenchymal Stem Cells: Integrated Analysis of Inflammatory Genes, Regulatory MicroRNAs, and DNA Methylation 15 29 118635 10.30483/rjm.2026.254766.1519 EN Hossein Malekan Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Ramin Raoufinia Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran. Workplace Health Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran. Ghazal Alyari Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Amir Reza Bagheri Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Reza Mousavi Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran. Ayda Yavari Kondori Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Hamid Reza Rahimi Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Metabolic Syndrome Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran. 0000-0002-2269-4109 Journal Article 2026 04 30 <strong>Background:</strong> Mesenchymal stem/stromal cells (MSCs) exert therapeutic effects largely through immunomodulatory and paracrine mechanisms. Pharmacological preconditioning strategies have been proposed to enhance MSC functionality and therapeutic efficacy. Curcumin possesses anti-inflammatory and epigenetic regulatory properties; however, the effects of curcumin nanomicelles on inflammation-associated genes, regulatory microRNAs, and DNA methylation patterns in Wharton's jelly-derived MSCs (WJ-MSCs) remain incompletely understood. <br><br><strong>Objectives</strong>: This study investigated the molecular effects of curcumin nanomicelles on inflammatory regulatory pathways in WJ-MSCs.<br><br><strong>Methods</strong>: WJ-MSCs were isolated from human umbilical cords and characterized by flow cytometry and multilineage differentiation assays. Cell viability following exposure to curcumin nanomicelles was assessed using the MTT assay. Cells were treated with 20 μM and 70 μM curcumin nanomicelles for 24 h. Expression levels of IκBα, TGF-β1, miR-21, and miR-146a were evaluated by quantitative real-time PCR. Promoter methylation status of IκBα and TGF-β1 was analyzed using methylation-sensitive high-resolution melting (MS-HRM).<br><br><strong>Results</strong>: Curcumin nanomicelles induced dose-dependent molecular alterations in WJ-MSCs. Treatment with 70 μM significantly increased IκBα expression and reduced miR-21 expression compared with untreated controls (P < 0.05). TGF-β1 expression was significantly increased following treatment with 20 μM curcumin nanomicelles, whereas no significant change was observed at 70 μM. miR-146a expression was significantly decreased at both tested concentrations. Despite these transcriptional and post-transcriptional changes, no significant alterations in promoter methylation patterns of either IκBα or TGF-β1 were detected after 24 h of treatment.<br><br><strong>Conclusion</strong>: Curcumin nanomicelles modulated inflammation-associated gene expression and regulatory microRNAs in WJ-MSCs without inducing detectable promoter methylation changes in IκBα or TGF-β1. These findings suggest that the early molecular effects of curcumin nanomicelles are predominantly mediated by transcriptional and post-transcriptional mechanisms. The observed modulation of inflammatory regulatory pathways supports further investigation of curcumin nanomicelles as a potential MSC preconditioning strategy; however, additional protein-level, functional, and disease-model studies are required to determine their translational relevance. https://journal.razavihospital.ir/article_118635_18ef97b44e26908443839317f815266e.pdf