👤 Mahmoud Barati

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

Diabetes, a prevalent chronic disease known for its complications such as cardiovascular issues, eye damage, and neuropathy, has increasingly been linked to an elevated risk of Alzheimer's disease and cognitive impairment. Individuals with diabetes are approximately twice as likely to experience cognitive dysfunction compared to the general population. This heightened risk is potentially mediated by factors such as hypoglycemic episodes, which can negatively impact brain function, particularly the hippocampus, a key region for memory. Furthermore, shared molecular and cellular characteristics between diabetes and Alzheimer's, such as the role of insulin in amyloid plaque formation, suggest a direct link between insulin resistance in the brain and the development of Alzheimer's-related pathology. This study investigates the potential of two commonly prescribed diabetes medications, Show less

Polymorphisms in the melanocortin 4 receptor (MC4R) gene with occurrence and progression of chronic diseases such as obesity and cardiovascular disease (CVD) have long been addressed but there is a lack of evidence for complex interrelationships, including direct and indirect effects of these variables. This review specifically focuses on studying the effects of healthy diet interaction and MC4R polymorphisms on the development of CVD. The quantity and quality of carbohydrates and proteins consumed are related to obesity susceptibility and cardiometabolic risk factors. A healthy dietary pattern such as a Mediterranean dietary can modulate the association between MC4R polymorphisms (rs17782313) and the risk of CVDs. Also, the Nordic diet can reduce lipid profiles such as low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels. On the other hand, MC4R interaction with the dietary inflammatory index decreases high-density lipoprotein cholesterol levels and increases LDL-C and triglyceride (TG) levels. Additionally, the DASH diet decreases TG, atherogenic index of plasma, systolic blood pressure, diastolic blood pressure, and serum glucose. The interaction between MC4R genes and diets plays an important role in the development of CVD. Adherence to healthy diets such as the Mediterranean, Nordic, Anti-inflammatory, and Dash diets might be an efficient strategy to prevent CVD. The potential for personalized diets to be developed for the treatment and prevention of CVD and its related comorbidities is expected to expand as this field develops. Show less

Anhedonia or inability to experience pleasure is the sign of various neuropsychiatric conditions. Current treatment options do not provide adequate control of anhedonia. The present study was conducted to evaluate the protective effects of valproic acid (VPA) as a nonspecific histone deacetylase (HDAC) inhibitor to reverse the effects of stress on induction of anhedonia and explore possible mechanisms. To induce anhedonia, a rat model of chronic unpredictable mild stress (CUMS) was established. Animals were assigned into no stress, stress (6 weeks of CUMS) and two treatment groups. VPA treatment was carried out for 4 continuous weeks (200 mg/kg/day). Behavioral assessments were performed using sucrose consumption (SCT) and new object recognition (NOR) tests. The expression of genes was evaluated using qRT-PCR. The cell density was determined using Nissl staining. Rats with CUMS showed depressive-like behaviors and impaired memory performance compared with the non-stressed group (p < 0.01). Moreover, they had significantly higher levels of HDAC3 and MC4R expression in the nucleus accumbens (NAc) compared to the non-stressed group (p < 0.01). The NAc cell density was significantly higher in the non-stressed rats (p < 0.05). Corticosterone plasma level was increased in the CUMS compared to the non-stressed group (p < 0.05). In the CUMS + VPA subgroup, the corticosterone (CORT) plasma level was lower compared with the CUMS + Saline and/or the CUMS groups (p < 0.05). These findings suggest that VPA can improve anhedonia and stress. Although the protective effect of VPA might link to decreasing HDAC3 and MC4R genes expression in NAc. Show less

Chronic lymphocyte leukemia (CLL) is a B-cell malignancy resisted to apoptosis. Recently, some studies indicated that cytokines such as interleukin 27 (IL-27) can reduce B-cell proliferation. The aim of this study is to evaluate the mechanism underlying the proapoptotic effect of IL-27 on B cells of patients with CLL in comparison with B cells of normal subjects. The effect of IL-27 on the antitumor activity of natural killer (NK) and T cells was also evaluated. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CLL and 15 normal subjects. B cells and PBMCs were cocultured with IL-27 and B cells apoptosis to evaluate proliferation. Both messenger RNA and protein expression of IL-27 and IL-27 receptor were determined using flow cytometry and real-time polymerase chain reaction analysis. To evaluate the apoptotic effect of IL-27 on B cells of patients with CLL, Annexin V-FITC and 7-AAD (BioLegend) fluorescent dyes were used. In addition, the IL-27 effect on activation of T cell and NK cell was determined by determining CD96 molecule expression. IL-27 and IL-27 receptor expression in patients with CLL was significantly lower than that of normal subjects (p < .05). IL-27 enhanced apoptosis of B cells in patients with CLL (p < .05) but this effect was not significantly observed in B cells of normal subjects (p > .05). Consequently, IL-27 reduced the proliferation of B cells and enhanced NK cell activity (p < .05). IL-27, through inducing apoptosis, can exert an inhibitory effect on cancer B cells of CLL patients with minimal effect on normal B cells. Show less