👤 Zahra Shahveghar Asl

Multiple sclerosis (MS) is a debilitating neurological disorder involving concurrent immune-mediated demyelination and progressive neurodegeneration. Although disease-modifying therapies (DMTs) effectively modulate peripheral immune responses and reduce relapse rates, they are ineffective at halting disease progression and promoting central nervous system (CNS) repair. This review outlines a new therapeutic approach that targets two important microRNAs: miR-219, which stimulates oligodendrogenesis and remyelination, and miR-146a, which regulates innate immune responses and neuroinflammation. We present compelling evidence showing that the dysregulation of these microRNAs establishes a cycle of inflammatory damage and regenerative failure in chronic MS lesions. Preclinical models show that supplementing with miR-219 drives oligodendrocyte precursor cell (OPC) differentiation and myelin restoration by repressing critical inhibitors, such as PDGFRα and LINGO-1. Concurrently, miR-146a modulates neuroinflammatory cascades by regulating the NF-κB pathway, promoting the polarization of microglia toward a protective M2 phenotype, and enhancing OPC maturation. Despite its therapeutic potential, there are significant challenges to its translation, including optimizing CNS-targeted delivery systems, navigating microRNA pleiotropy, and establishing biomarker-driven treatment paradigms. We propose that a dual-targeting approach leveraging advanced nanocarriers for spatiotemporal microRNA delivery represents a transformative frontier in MS therapeutics, potentially bridging the critical gap between immunomodulation and genuine neurorestoration. Show less

Chronic liver disease (CLD) influences the levels of diverse metabolites that may be related to its pathogenesis. The study aimed to indicate the relation between CLD and the levels of phospholipids. In this systematic review, PRISMA guidelines were considered for reporting the results. Up to November 2024, the databases of MEDLINE (through PubMed), Scopus, Web of Science, and Google Scholar were searched. Case-control (CC) and cross-sectional (CS) studies explored the link between CLD and serum phospholipids. The Newcastle-Ottawa scale (NOS) for CC studies and the modified NOS scale for CS studies were applied to evaluate the quality of the included articles. A total of 11304 articles were included. Eleven thousand duplicates were removed, 9304 studies were excluded, and 343 full-text articles were reviewed. Fifteen CC studies and four CS studies were included in this study. Quality assessment using NOS revealed most studies had low to moderate risk of bias, with scores ranging from 4 to 8 out of 9.The included studies verified a significant association between the levels of total PL (TPL), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA), lysophosphatidylcholine (LPC), lysophosphatidylinositol (LPI) and lysophosphatidic acid (LPA) and liver diseases., with reported odds ratios ranging from 1.44 to 2.51 and correlation coefficients from -0.58 to 0.62. Phospholipid levels are associated with liver diseases. It is important to identify noninvasive ways to diagnose biological risk factors in patients with liver damage so they can be targeted for early treatment. Most of the included studies revealed significant alteration of phospholipid levels in CLD. Thus, the lipidome can predict liver dysfunction and prevent its attributed complications. Show less