In spite of prosperous experiences in MS therapy, the future research, hopefully, will bring substantial improvements in the understanding and approaches of MS therapy.

With the development of novel treatments for autoimmune disorders, it has become a popular research focus which mesenchymal stem cells (MSCs) have the capacity to counteract with autoimmune diseases progression. One of the underlying mechanisms behind their activities is the release of extracellular vesicles especially exosomes. MSC-derived exosomes are hypoimmunogenic nanocarriers which contain numerous immunoregulatory factors and similar to other exosomes, are able to pass through boundaries like the blood-brain barrier (BBB). Accumulating evidence provided by animal studies has demonstrated that MSC-derived exosomes, as a novel therapy, can re-induce self-tolerance, without subsequent complications reported for other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases. Here, we briefly describe the biological characteristics of MSC-derived exosomes and review the experimentally verified outcomes for autoimmune disease therapy purposes.

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Multiple sclerosis (MS) is an autoimmune disease which is characterized by neuroaxonal degeneration in the central nervous system. Impaired function of regulatory T cells (Tregs) is believed to be an underlying pathogenic mechanism in MS. Tregs is able to release exosomes, which contain a considerable amount of protein and RNA. Exosomes are capable of transporting their content to other cells where the released content exerts biological functions. Here, we investigated whether Tregs exosomes of RRMS patients or healthy controls might regulate the proliferation or survival of T lymphocytes. Regulatory T cells derived from MS patients or healthy controls were cultured for 3 days and exosomes were purified from supernatants. Treg-derived exosomes were co-cultured with conventional T cells (Tconv). The percentages of Tconv proliferation and apoptosis were measured. Our findings showed that the percentage of proliferation suppression induced by exosomes in patients compared to healthy controls was 8.04 ± 1.17 and 12.5 ± 1.22, respectively, p value = 0.035. Moreover, the rate of Tconv apoptosis induced by exosome of MS patient was less than healthy controls (0.68 ± 0.12 vs. 1.29 ± 0.13; p value = 0.015). Overall, Treg-derived exosomes from MS patients and healthy controls suppressed the proliferation and induced apoptosis in Tconv. However, the effect of MS-derived exosomes was significantly less than healthy controls. Our results point to an alternative Treg inhibitory mechanism which might be important in immunopathogenesis of MS. Although, the cause of the exosomal defect in MS patients is unclear, manipulation of patients' Treg-derived exosomes to restore their suppressive activity might be considered as a potential therapeutic approach. Graphical abstract ᅟ.

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Invasion of auto-reactive CD4+ T cells especially Th17 into central nervous system (CNS) is an underlying pathogenic mechanism in multiple sclerosis (MS). CD4+ T cells release exosomes which are enriched in microRNAs, reflective of cell’s physiological or pathological condition. Thus exosomes could be potent agents to provide quantitative and qualitative information about involved cells in MS. We investigated the expression of pathogenic microRNAs in T cells-derived exosomes of MS patients or healthy controls. Conventional T cells (Tconv) derived from relapsing-remitting (RR) MS patients (n=10) and healthy controls (n=10) were purified and cultured for 3 days by soluble anti-CD3/CD28. Exosomes were purified from cultured-T cells supernatants. The expression levels of exosomal miR-146a, miR-29a, miR-155, and miR-326 were quantified by real-time PCR. A statistically significant increased expression of miR-326 in Tconv-derived exosomes was observed in RRMS patients as compared with controls (7.5±1.88vs 2.51±0.9 p=0.03), On the contrary, no differences were found in the expression levels of miR-155, miR-146a, and miR-29a, in Tconv-derived exosomes of  patients as compared with controls (p>0.05).  Our results point to altered expression in exosome-derived microRNAs. MiR-326 was previously shown to play a role in the immunopathogenesis of MS by inducing TH17 differentiation and maturation. Therefore, miR-326 containing exosomes might also be a potential clinical target in course of MS. Moreover, the deregulation of this miRNA in exosomes may serve as a diagnostic and prognostic biomarker.

Background In this study, the ability of antimicrobial photodynamic therapy (aPDT) as a treatment approach and adjuvant therapy using curcumin-poly (lactic-co-glycolic acid) nanoparticles (Cur@PLGA-NPs) to inactivate Coronavirus disease 2019 (COVID-19) in plasma was investigated. Furthermore, to verify whether the quality requirement of aPDT-treated plasma is acceptable, the differences of the levels of clotting factors, total plasma proteins, and anti-A and/or anti-B antibodies titrations in plasma of patient before and after aPDT treatment were investigated. Materials and Methods Cur@PLGA-NPs was synthesized using Electrospinning process and characterized by different analysis including Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), and Fourier Transform Infrared (FTIR) spectroscopy assays. The presence of the SARS-CoV-2 in the plasma samples of patients suspected of having COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Then, the treated plasma samples with Cur@PLGA-NPs plus blue laser were exposed to Vero cells. Eventually, cell cytotoxicity and apoptotic effects of treated Vero cells were evaluated. Levels of clotting factors including prothrombin time (PT) and activated partial thromboplastin time (APTT), total plasma proteins, and anti-A and/or anti-B antibodies measurements were performed using the coagulometer, method of Bradford, and titration procedure, respectively. Results The presence of SARS-CoV-2 was positive in 84.3 % of samples. Different concentrations of Cur@PLGA-NPs (3, 5, 7, and 10 % wt.), the irradiation times of blue laser (1, 3, and 5 min), and aPDT with the maximum dosed of blue laser light (522.8 J/cm 2 ) plus 10 % wt. Cur@PLGA-NPs had no cytotoxicity. Although there were significant cell degradation and apoptotic effects in treated Vero cells with treated plasma using 10 % wt. Cur@PLGA-NPs, and a blue laser at an energy density of 522.8 J/cm 2 , no visible changes in cells and apoptosis were observed following aPDT. Total plasma protein content, PT, APTT, and anti-A and/or anti-B antibodies titers showed no significant changes (P > 0.05 for all comparisons) in treated plasma as compared to untreated plasma. Conclusion aPDT exhibited in vitro anti-COVID-19 activities in the treated plasma containing SARS-COV-2 without Vero cell apoptosis and any adverse effects on plasma quality in aPDT-exposed plasma.

BackgroundToday, the plant Prosopis farcta is frequently used for traditional medicinal purposes. The aim of this study was the identification of luteolin in P. farcta extract (PFE) and to evaluate its effect on morphine discontinuation syndrome in rats.Material/MethodsUsing high-performance liquid chromatography (HPCL), luteolin was evaluated in PFE. The frequency of behavioral symptoms of morphine withdrawal (jumping, rearing, and teeth chattering) induced by naloxone challenge were illustrated in morphine-dependent rats receiving PFE, luteolin, saline, or clonidine. LD50 of PFE and luteolin was 540 mg/kg and 150 mg/kg, respectively. Signs of behavioral morphine withdrawal in rats were significantly inhibited by chronic co-administration of PFE, luteolin, or clonidine with morphine.ResultsThis study showed that PFE was less effective than clonidine at a dose of 100 mg/kg, and at doses of 200 mg/kg and 300 mg/kg it was comparable to clonidine, and did not show a significant difference in the reduction of morphine withdrawal symptoms. Luteolin was comparable in 30 mg/kg, 60 mg/kg, and 90 mg/kg with clonidine to reduce the frequency of morphine withdrawal symptoms. PFE can be used as a source of luteolin.ConclusionsThe study findings suggest that PFE and luteolin might reduce the signs of narcotic withdrawal. Due to a similar effect to clonidine, its mechanism of action might be through the protein kinase A pathway and might have human therapeutic potential.