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Experimental autoimmune encephalomyelitis (EAE) is an induced autoimmune disease widely used as an animal model for multiple sclerosis, which is mainly characterized by demyelination, axonal loss, as well as neurodegeneration of central nervous system (CNS). T-helper (Th) 17 cell that generate interleukin-17 (IL-17) plays a key role in its pathogenesis. Their activity and differentiation are tightly regulated by some cytokines and transcription factors. Certain microRNAs (miRNAs) are involved in the pathogenesis of various autoimmune disorders, including EAE. Our research detected a novel miRNA that can regulate EAE. According to the results, during EAE, the expression of miR-485 notably lowered, and STAT3 was significantly increased. It was discovered that miR-485 knockdown in vivo upregulated Th17-associated cytokines and aggravated EAE, while the overexpressed miR-485 down-regulated Th17-associated cytokines and mitigated EAE. The up-regulation of miRNA-485 in vitro inhibited Th17-associated cytokines expression within EAE CD4+ T cells. Furthermore, as revealed by target prediction and dual-luciferase reporter assays, miR-485 directly targets STAT3, a gene that encodes a protein responsible for Th17 generation. Overall, miR-485 exert vital functions in Th17 generation and EAE pathogenesis., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disorder of the central nervous system. Accumulating evidence has underscored the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exos) containing bioactive compounds in MS. Herein, the current study sought to characterize the mechanism of BMSC-Exos harboring miR-367-3p both in BV2 microglia by Erastin-induced ferroptosis and in experimental autoimmune encephalomyelitis (EAE), a typical animal model of MS. Exosomes were firstly isolated from BMSCs and identified for further use. BV2 microglia were co-cultured with miR-367-3p-containing BMSC-Exos, followed by an assessment of cell ferroptosis. Mechanistic exploration was furthered by the interaction of miR-367-3p and its downstream regulators. Lastly, BMSC-Exos harboring miR-367-3p were injected into EAE mice for in vivo validation. BMSC-Exos carrying miR-367-3p restrained microglial ferroptosis in vitro. Mechanistically, miR-367-3p could bind to Enhancer of zeste homolog 2 (EZH2) and restrain EZH2 expression, leading to the over-expression of solute carrier family 7 member 11 (SLC7A11). Meanwhile, over-expression of SLC7A11 resulted in Glutathione Peroxidase 4 (GPX4) activation and ferroptosis suppression. Ectopic expression of EZH2 in vitro negated the protective effects of BMSC-Exos. Furthermore, BMSC-Exos containing miR-367-3p relieved the severity of EAE by suppressing ferroptosis and restraining EZH2 expression in vivo. Collectively, our findings suggest that BMSC-Exos carrying miR-367-3p brings about a significant decline in microglia ferroptosis by repressing EZH2 and alleviating the severity of EAE in vivo, suggesting a possible role of miR-367-3p overexpression in the treatment strategy of EAE. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is marked by inflammation and damage to the myelin sheath surrounding nerve fibers. Recent studies have highlighted the therapeutic value of exosomes (Exos) obtained from bone marrow mesenchymal stem cells (BMSCs) in MS treatment. These BMSC-Exos contain biologically active molecules that show promising results in preclinical evaluations. The aim of this study was to investigate the mechanism of BMSC-Exos containing miR-23b-3p in both LPS-stimulated BV2 microglia and in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Exos were isolated from BMSCs, and their effects were evaluated in vitro by co-culturing with BV2 microglia. The interaction between miR-23b-3p and its downstream targets was also explored. The efficacy of BMSC-Exos was further verified in vivo by injecting the Exos into EAE mice. The results showed that BMSC-Exos containing miR-23b-3p reduced microglial pyroptosis in vivo by specifically binding to and suppressing the expression of NEK7. In vivo, BMSC-Exos containing miR-23b-3p alleviated the severity of EAE by decreasing microglial inflammation and pyroptosis via the repression of NEK7. These findings provide new insights into the therapeutic potential of BMSC-Exos containing miR-23b-3p for MS., Competing Interests: Declaration of Competing Interest No other disclosures were reported., (Copyright © 2023. Published by Elsevier Inc.)

Optic neuritis and retinal damage are common manifestations of multiple sclerosis (MS). Pterostilbene (PT) has been used to treat multiple diseases for its anti-inflammatory, anti-apoptosis and neuroprotective activities. This study aimed to investigate whether PT exerts a therapeutic effect on optic neuritis and retinal damage triggered by MS. Here, experimental autoimmune encephalomyelitis (EAE), an experimental model for MS, was induced in female C57BL/6 mice by immunizing with MOG 35-55 peptide and treating with pertussis toxin. The mice were intraperitoneally injected with 20 mg/kg and 40 mg/kg PT once daily for 25 days at 24 h post immunization. We found that PT alleviated EAE severity and delayed EAE onset. Moreover, PT mitigated EAE-induced optic nerves and retinal inflammation, as indicated by the decreased Iba-1 + and GFAP + cells and mRNA levels of interleukin-6, tumor necrosis factor-α and interleukin-1β and the increased Iba-1 + sirtuin 1 (SIRT1) + and GFAP + SIRT1 + cells in the optic nerves and retina. PT also protected the optic nerves against demyelination and axonal loss and the retina against disorders in retinal morphology and apoptosis of retinal ganglion cells. High-dose PT had a more significant effect on protection of the optic nerves and retina in EAE than low-dose PT. In addition, PT activated SIRT1 signaling in the optic nerves and retina. Notably, EX-527, an inhibitor of SIRT1, reversed the effect of high-dose PT on the optic nerves and retina, indicating that PT exerted the protective effect via activating SIRT1 signaling. This study provides a potential candidate for treating MS., (Copyright © 2022. Published by Elsevier Ltd.)