Epstein-Barr virus-encoded BART9 and BART15 miRNAs are elevated in exosomes of cerebrospinal fluid from relapsing-remitting multiple sclerosis patients.

Epstein-Barr virus (EBV) infection is approved as the main environmental trigger of multiple sclerosis (MS). In this path, we quantified ebv-miR-BART9-3p and ebv-miR-BART15 in exosomes of cerebrospinal fluid (CSF) of untreated relapsing-remitting MS (RRMS) patients in comparison with the control group. Interestingly, patients displayed significant upregulation of ebv-miR-BART9-3p (18.4-fold) and ebv-miR-BART15 (3.1-fold) expression in CSF exosomes. Moreover, the expression levels of hsa-miR-21-5p and hsa-miR-146a-5p were found to be significantly elevated in the CSF samples obtained from the patient group compared to those obtained from the HC group. The levels of Interferon-gamma (IFN-γ), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-ß), and tumor necrosis factor-alpha (TNF-α) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-ß (8.5-fold), followed by IL-23 (3.9-fold) in CSF exosomes. These findings are in agreement with the association between EBV infection and inflammatory cytokines induction. Furthermore, the ratios of TGF-ß: TNF-α and TGF-ß: IFN-γ attained values of 4 to 16.4 and 1.3 to 3.6, respectively, in the CSF exosomes of the patients, in comparison to those of the control group. These findings show EBV activity in RRMS patients is different from that of healthy ones. Elevation of ebv-miR-BART9-3p, ebv-miR-BART15, and inflammatory cytokines expression in CSF exosomes in RRMS patients provides a substantial link between EBV activity and the onset of the disease, as well as the transition from EBV infection to MS.

Exosome Content-Mediated Signaling Pathways in Multiple Sclerosis.

Exosomes are small extracellular vesicles with a complex lipid-bilayer surface and 30-150 nm diameter. These vesicles play a critical role in intercellular signaling networks during physiopathological processes through data trafficking and cell reprogramming. It has been demonstrated that exosomes are involved in a variety of central nervous system (CNS) disorders such as multiple sclerosis (MS). Exosome mediators' cell-to-cell communication is possibly by delivering their contents such as proteins, RNAs (coding and non-coding), DNAs (mitochondrial and genomic), and transposable elements to the target cells. Exosomal microRNAs (miRNAs) differ in their expression patterns in MS disease, thereby providing novel diagnostic and prognostic biomarkers and therapeutic options for better treatment of MS disease. Furthermore, these microvesicles are non-immunogenic and non-toxic therapeutic tools for transferring miRNAs across the blood-brain barrier (BBB). Collectively, exosomes could be used as novel drug delivery devices for the treatment of MS patients. This review summarized research regarding the exosomes from serum, plasma, PBMC, and other cells in MS patients and experimental models. We also provide a critical view of exosome content-mediated signaling pathways in MS, including TNF-α, TGF-ß, NF-κB, and Wnt pathways. The use of exosomes as a therapeutic potential in MS has also been discussed.

The effect of probiotic supplementation on the clinical and para-clinical findings of multiple sclerosis: a randomized clinical trial.

Multiple Sclerosis (MS) is a chronic demyelination disease of the central nervous system (CNS). The gut-brain axis involves communication between the nervous, endocrine, and immune systems. Probiotics can positively impact immune and inflammatory responses by regulating gut microbiota. A total of 40 MS patients (average age of 34.38 ± 6.65) were examined to determine the effect of the Saccharomyces boulardii supplement for four months compared to a placebo. The results showed that the Saccharomyces boulardii significantly decreased the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) compared to the placebo (P < 0.001). The serum antioxidant capacity (TAC) also increased significantly in the probiotic group compared to the placebo (p = 0.004). Both the probiotic and placebo groups showed a reduction in the oxidative stress indicator malondialdehyde (MDA), but there was no significant difference between the two groups. Pain intensity (measured by Visual Analogue Scale) and fatigue severity (measured by Fatigue Severity Scale) significantly decreased in the probiotic group compared to the placebo (p = 0.004 and p = 0.01, respectively). The probiotic group experienced significant improvement in some quality of life scales (measured by 36-Item Short Form Survey) and somatic and social dysfunction subscale of General Health Questionnaire scores compared to the placebo group (p = 0.01). The study suggests that the Saccharomyces boulardii probiotic supplement may benefit inflammatory markers, oxidative stress indicators, pain, fatigue, and quality of life in MS patients.

Insulin resistance is associated with cognitive dysfunction in multiple sclerosis patients: A cross-sectional study.

Multiple sclerosis (MS) is a progressive inflammatory neurodegenerative disease of the nervous system accompanied by demyelination. MS-associated cognitive impairments mainly involve recent memory, information processing speed, stable memory, and executive function. Moreover, MS is associated with impaired glucose and insulin metabolism, which can exacerbate cognitive decline. The present study aimed to compare the cognitive status of MS patients with and without insulin resistance. In this cross-sectional study, 74 relapsing-remitting multiple sclerosis diagnosed patients were enrolled. Indicators of insulin resistance, including fasting blood glucose, insulin level, and homeostatic model assessment of insulin resistance (HOMA-IR) index, were measured. They were then divided into two groups based on the results of the HOMA-IR index. Cognition status was evaluated by the minimal assessment of cognitive function in multiple sclerosis battery. The prevalence of insulin resistance was 37.8%, and the prevalence of cognitive decline was estimated to be 67.56%. Mean scores of the California verbal learning test (CVLT), CVLT delayed free recall, controlled oral word association test, and judgment of line orientation tests were significantly lower in MS patients with insulin resistance than without. In addition, a negative correlation was demonstrated between the results of the CVLT, CVLT delayed free recall, controlled oral word association test, judgment of line orientation tests, brief visuospatial memory test, and Delis-Kaplan executive function system sorting tests and fasting insulin levels. Greater verbal memory and spatial comprehension impairments were observed in MS patients with insulin resistance.

Multiplex Analysis of Cerebrospinal Fluid and Serum Exosomes MicroRNAs of Untreated Relapsing Remitting Multiple Sclerosis (RRMS) and Proposing Noninvasive Diagnostic Biomarkers.

Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for neurodegenerative diseases. In this study, we aimed to detect relapsing-remitting multiple sclerosis (RRMS)-specific miRNAs in cerebrospinal fluid (CSF) and serum exosomes with diagnostic potential. One ml of CSF and serum sample were collected from each of the 30 untreated RRMS patients and healthy controls (HCs). A panel of 18 miRNAs affecting inflammatory responses was applied, and qRT-PCR was conducted to detect differentially expressed exosomal miRNAs in CSF and serum of RRMS patients. We identified that 17 out of 18 miRNAs displayed different patterns in RRMS patients compared to HCs. Let-7 g-5p, miR-18a-5p, miR-145-5p, and miR-374a-5p with dual pro-inflammatory and anti-inflammatory actions and miR-150-5p and miR-342-3p with anti-inflammatory action were significantly upregulated in both CSF and serum-derived exosomes of RRMS patients compared to corresponding HCs. Additionally, anti-inflammatory miR-132-5p and pro-inflammatory miR-320a-5p were significantly downregulated in both CSF and serum-derived exosomes of RRMS patients compared to HCs. Ten of 18 miRNAs were differentially expressed in CSF and serum exosomes of the patients. Furthermore, miR-15a-5p, miR-19b-3p, and miR-432-5p were upregulated, and miR-17-5p was downregulated only in CSF exosomes. Interestingly, U6 housekeeping gene was differentially expressed in CSF and serum exosomes, in both RRMS and HCs. As the first report describing CSF exosomal miRNAs expression profile compared to that of serum exosomes in untreated RRMS patients, we showed that CSF and serum exosomes are not identical in terms of biological compounds and display different patterns in miRNAs and U6 expression.

Safety and Effectiveness of Cinnomer® on Disease Characteristics, Depression, and Quality of Life of Patients with Multiple Sclerosis: A Phase IV, Post-marketing, Prospective, Multicenter Study.

BACKGROUND: Every patient diagnosed with definite multiple sclerosis (MS) should begin disease modifying therapies. Cinnomer® contains 40 mg glatiramer acetate (GA) and is available in prefilled syringes and autoinjector devices. METHODS: A phase IV multicenter study was conducted to explore the safety and effectiveness of Cinnomer® in the treatment of MS. Study-related data were collected for 14 months. RESULTS: Totally, 368 Iranian relapsing-remitting MS patients in nine cities were enrolled. The patients were either treatment naïve (n=191) or switchers (n=177). Cinnomer® treatment was associated with a significant reduction in annual relapse rate (ARR) (RR: 0.65, 95% CI: 0.43, 0.98). Final mean Expanded Disability Status Scale (EDSS) scores showed improvement from baseline (difference: -0.21, 95% confidence interval (CI): -0.34, -0.08). There was a significant decrease in gad-enhancing lesions during treatment (difference: -0.38, 95% CI: -0.64, -0.12). The mean score for the depression measure (21-item BDI-II questionnaire) significantly improved (difference: -2.39, 95% CI: -3.74, -1.03). There was a significant change in the "psychological well-being" dimension (P=0.02) (in line with BDI-II scores) and "rejection" MusiQoL dimensions (P=0.04). The adverse events documented throughout the study were not unexpected for GA and were principally not serious. CONCLUSION: Safety measures were in line with the known profiles of GA. The results suggest that Cinnomer® is effective with respect to clinical outcomes and from the patient's perspective and in reducing MRI-measured MS activity.

The expression pattern of VISTA in the PBMCs of relapsing-remitting multiple sclerosis patients: A single-cell RNA sequencing-based study.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Dysregulated immune responses have been implicated in MS development. Growing evidence has indicated that inhibitory immune checkpoint molecules can substantially regulate immune responses and maintain immune tolerance. V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule that can suppress immune responses; however, its expression pattern in the peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) has not thoroughly been studied. Herein, we evaluated Vsir expression in PBMCs of RRMS patients and characterized the expression pattern of the Vsir in the PBMCs of MS patients. Besides, we investigated the effect of fingolimod, IFNß-1α, glatiramer acetate (GA), and dimethyl fumarate (DMF) on Vsir expression in PBMCs of RRMS patients. Our results have shown that Vsir expression is significantly downregulated in the PBMCs of patients with RRMS. Besides, the single-cell RNA sequencing results have demonstrated that Vsir expression is downregulated in classical monocyte, intermediate monocytes, non-classical monocytes, myeloid DCs (mDC), Plasmacytoid dendritic cells (pDCs), and naive B-cells of PBMCs of MS patients compared to the control. In addition, DMF, IFNß-1α, and GA have significantly upregulated Vsir expression in the PBMCs of RRMS patients. Collectively, the current study has shed light on Vsir expression in the PBMCs of MS patients; however, further studies are needed to elucidate the significance of VISTA in the mentioned immune cells.

Pregnancy outcome in patients with neuromyelitis optica spectrum disorder treated with rituximab: A case-series study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a neuroinflammatory disorder with a tendency to affect the spinal cord and optic nerves. As NMOSDs have a predilection for women of reproductive age and adopt an aggressive course during pregnancy, appropriate treatment strategies before conception and during pregnancy should be well-considered. CASE PRESENTATION: In this report, the pregnancy outcome of eight pregnancies following rituximab treatment was assessed, which led to 50% live births with mean birth weight of 2777.50 (SD: 545.92) grams. Two patients had abortions due to doctor's recommendation. One pregnancy led to intrauterine fetal death (IUFD) due to nuchal cord. No spontaneous abortions were encountered. Two patients received rituximab during pregnancy. No major malformations or serious neonatal infections were encountered. CONCLUSION: Rituximab should be administered by caution in NMOSD patients who want to be pregnant and the probable adverse effects of the drug should be discussed by patients.

An interdependence between GAPVD1 gene polymorphism, expression level and response to interferon beta in patients with multiple sclerosis.

Interferon-ß (IFN-ß) is among the first drugs used for reducing the symptoms of multiple sclerosis (MS). Many studies show that the genetic predisposition of patients might modulate their response to IFN-ß treatment. In this study GAPVD1 gene expression and the genotyping of rs2291858 variant were analysed in 100 responder and 100 non-responder patients with MS treated using IFN-ß. Moreover, rs2291858 genotyping was performed for 200 patients with MS and 200 healthy controls. GAPVD1 expression was significantly increased in the responder patients than in non-responders and the distribution of rs2291858 polymorphism was significantly different between them. The GAPVD1 expression level in AA genotype of the responder group was higher than that in other genotypes of these two groups. The results show that the GAPVD1 expression level and rs2291858 genotype probably affect the response to IFN- ß in patients with MS.

The expression analyses of RMRP, DDX5, and RORC in RRMS patients treated with different drugs versus naïve patients and healthy controls.

Although T helper 17 (Th17) lymphocytes protect mucosal barriers against infections, they have been implicated in the development of multiple sclerosis (MS). RORC and DDX5 can regulate Th17 differentiation and the development of MS. Since RMRP, as a long non-coding RNA (lncRNA), can mediate the RORC-DDX5 complex, this lncRNA can be involved in developing MS. This study investigated the expression levels of RORC, DDX5, and RMRP in treatment-naïve relapsing-remitting multiple sclerosis (RRMS) patients, healthy controls, and RRMS patients treated with IFNß-1α or fingolimod, or dimethyl fumarate (DMF), or glatiramer acetate (GA). There was substantial up-regulation in the expression of RORC, DDX5, and RMRP in treatment-naïve RRMS patients compared to healthy controls. Among the comparisons of their expressions in the different groups of treated patients with treatment-naïve patients, only the down-regulation of the RMRP expression level was significant in IFNß-1α-treated patients. Also, these changes were more pronounced in female patient groups. Our analyses have highlighted the high diagnostic value of RORC, DDX5, and RMRP in treatment-naïve RRMS patients. Furthermore, RMRP has demonstrated moderate positive correlations with the expression of DDX5 and RORC in treated RRMS patients.

Epigenetic mechanisms shape the underlining expression regulatory mechanisms of the STAT3 in multiple sclerosis disease.

OBJECTIVES: Immunological tolerance is mediated by CD4+CD25+ regulatory T (Treg) cells. Studies have shown that thymic and peripheral generations of Treg cells depend on the CD28 signaling pathway. T helper 17 (Th17) cells are involved in the pathophysiology of various inflammatory diseases. Cytokines, such as interleukin (IL)-6 and TGF-ß, regulate the reciprocal development of Th17 and Treg cells. In CD4+ T cells, signal transducer and activator of transcription 3 (STAT3) play a critical role in the induction of Th17 cell differentiation and inhibition of Treg cell development. RESULTS: In this study, we investigated the STAT3 methylation and gene expression status in patients with MS. Our study demonstrated that the level of STAT3 methylation decreased in relapsing-remitting MS patient compared to control groups, which the decreases were statistically significant. STAT3 gene expression increased in patient group relative to healthy one, and the increases were found to be statistically significant. According to our findings, it can be suggested that DNA hypermethylation of STAT3 affects the gene expression. In addition, there is a strong and significant negative correlation between the methylation status and mRNA level of STAT3.

Guillain-Barré syndrome in a patient infected with SARS-CoV-2, a case report.

BACKGROUND: The COVID-19 is a novel condition affecting all the world, so every manifestation of disease should be reported. Neurologic manifestations of the disease are increasingly identified and this will help clinician to improve their diagnostic and therapeutic skills in dealing with COVID-19 patients. CASE: In this article we report a 41-year-old male that developed ascending paresthesia and paralysis following infection with SARS-CoV-2 virus. Electrodiagnostic evaluation in patient revealed demyelinating type polyneuropathy and patient diagnosed as Guillain-Barré syndrome (AIDP type) and treated with IVIG which resulted in favorable response. CONCLUSIONS: Considering this report and other reports that are mentioned in our short review, there is probably causal relationship between COVID-19 and development of Guillain-Barré syndrome.

Connection of miR-185 and miR-320a expression levels with response to interferon-beta in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by neurodegeneration in the CNS. Interferon-beta (IFN-ß) is an FDA-approved drug used as the first-line treatment for relapse-remitting multiple sclerosis (RRMS). The exact mechanism of IFN-ß during the treatment of RRMS still remains unknown. Recently, many studies have shifted towards the role of miRNAs in the treatment of MS patients. METHODS: Herein, the expression level of miR-185-5p and miR-320a has been evaluated in order to candidate them as novel biomarkers for monitoring the response to IFN-ß therapy. For this purpose, one-hundred whole blood samples from patients with RRMS were collected, consisting of 50 responders and 50 non-responders to IFN-ß therapy. To predict the possible molecular mechanisms of IFN-ß and highlight the role of these miRNAs, in silico analysis was applied to enrich the signaling pathways which may be involved based on the target genes of miR-185-5p and miR-320a. RESULTS: It is identified that the differentially expressed miR-185-5p was statistically significant between the two treated groups with IFN-ß. Furthermore, MAPK signaling pathway was suggested as the main non-canonical pathway involved in IFN-ß therapy. CONCLUSION: miR-185-5p could be considered as a novel biomarker for monitoring the response to IFN-ß therapy.

miR-504 expression level is increased in multiple sclerosis patients responder to interferon-beta.

Multiple sclerosis is immune-mediated disease of the central nervous system characterized by demyelination in axons. IFN-ß is first-line treatment of MS. Biomarkers are needed for early prediction of responders and non-responders to therapy in the first month of treatment to avoid further disabilities. In this study, we analyzed the expression level of miR-504 and miR-711 in 52 IFN-ß responder patients in comparison to 53 non-responders. In the next step, the in-silico analysis was used to enrich related signaling pathways. The expression level of miR-504 was significantly higher in patients who respond to IFN-ß therapy, compared with non-responders and we obtain related statistically significant KEGG molecular signaling pathways. Our findings suggest that miR-504 can be considered as a novel biomarker for response to IFN-b therapy.

The effects of probiotic Saccharomyces boulardii on the mental health, quality of life, fatigue, pain, and indices of inflammation and oxidative stress in patients with multiple sclerosis: study protocol for a double-blind randomized controlled clinical trial.

BACKGROUND: The relationship between gut dysbiosis and inflammatory diseases including multiple sclerosis (MS) is presently recognized as an important health issue. It has been established that some bacterial probiotic strains are effective in treating MS. This study will investigate the effect of yeast probiotic Saccharomyces boulardii (SB) supplements on mental health, quality of life, fatigue, pain, and indices of inflammation and oxidative stress in MS patients. METHODS/DESIGN: In this double-blind randomized controlled two-group parallel trial, 50 MS patients who meet the inclusion criteria will be recruited from outpatient settings. They will be randomly allocated to 4 months of daily placebo or the SB probiotic intervention. Blood samples will be taken from each participant at the baseline and after the intervention period to assess inflammation and oxidative stress. The primary endpoint will be the changes in their mental health evaluated by the 28-item General Health Questionnaire. The secondary endpoints include changes in: (1) quality of life, evaluated by the 36-item Short Form Questionnaire, (2) fatigue, evaluated by the Fatigue Severity Scale, (3) pain, evaluated by a visual analogue scale, and (4) serum levels of indices of inflammatory stress (high-sensitivity C-reactive protein) and oxidative stress (malondialdehyde and total antioxidant capacity). Moreover, any adverse events and side effects due to the intervention will be documented. DISCUSSION: There is a need to discover safe and practical methods for managing the symptoms of MS. This trial will gather evidence on the effects of a probiotic. TRIAL REGISTRATION: Iranian Clinical Trial Registry, IRCT20161022030424N1 . Registered on 9 April 2018.

Nanocurcumin improves regulatory T-cell frequency and function in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a chronic incapacitating disease of the central nervous system, it has been reported that the disturbance in the development and function of Treg subpopulations is associated with the disability status in the RRMS. Accordingly, in the current study, the objective was to specify nanocurcumin effects on Treg cells frequency, and function in patients with RRMS. METHODS AND MATERIALS: 50 patients with RRMS were enrolled in this study in which 25 were treated for at least six months with nanocurcumin capsules while the other half received placebo capsules as the control group. The blood sample was collected prior to the administration of nanocurcumin and placebo capsules and following six months. At baseline and after a six-month treatment, the frequency of Treg lymphocytes, the expression of transcription factor related to these cells and the secretion levels of cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. RESULTS: A significant reduction was observed in the proportion of peripheral Treg cell frequency, and the levels of TGF-ß, IL-10 and FoxP3 expression in patients with RRMS. Our data revealed that the frequency of Treg cells (p = .0027), the expression of FoxP3 (p = .0005), TGF-ß (p = .0005), and IL-10 (p = .0002) and the secretion levels of the TGF-ß (p = .033), and IL-10 (p = .029) in cultured PBMCs are increased in nanocurcumin-treated group compared to placebo group. CONCLUSION: The results of the current work indicated that nanocurcumin is capable of restoring the frequency and function of Treg cells in MS patients.

Antidepressant Effects of a Persian Medicine Remedy on Multiple Sclerosis Patients: A Double-Blinded Randomized Clinical Trial.

BACKGROUND: Multiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system, is accompanied by some psychiatric disorders, one prominent example of which is depression. The aim of this study was to investigate the effects of a Persian herbal medicine treatment that contains Crocus sativus, Hypericum perforatum, Cinnamon verum, and Vitis vinifera on fatigue and sleep disorders in MS patients. MATERIALS AND METHODS: A Persian medicine remedy containing C.sativus, H.perforatum, C.verum, and V.vinifera was tested for its ability to improve the symptoms of depression in MS patients. This randomized double-blind clinical study was performed among 52 patients with MS who were allocated to their respective research groups through blocked randomization. The patients were treated for 4 weeks with either the drug or the placebo. To quantify the symptoms of depression, Beck depression inventory (BDI) was used. RESULTS: Forty-six patients completed the study. In the course of the study, as the primary outcome, BDI decreased in the drug group (p =0.000) and the placebo group (p =0.001) significantly, but the rate of change in the drug group was significantly higher than in the placebo group (-13.9 ± 8.6 vs. -3.9 ± 4.3, p =0.000). While analyzing time and treatment effect for BDI, significant decreases in BDI were observed for the drug group, but not in the placebo group (p = 0.001). CONCLUSION: The present study suggests that Persian medicine remedy treatment in combination with chemical drugs may improve depression symptoms in MS patients. More investigations are needed to discover the exact mechanisms and processes involved.

Nanocurcumin is a potential novel therapy for multiple sclerosis by influencing inflammatory mediators.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Inflammation has ever been thought as disadvantageous in the pathophysiology of MS. Nanocurcumin has been used as an anti-inflammatory compound. The aim of this study was to identify effects of nanocurcumin on inflammatory mediators in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Fifty MS patients were randomly divided into two groups. The test group received nanocurcumin capsule daily for 6 months. Simultaneously, the control group received placebo. Real-Time PCR was employed to detect the probable changes in gene expression levels of miRNAs, and miRNA-dependent targets, and also transcription factors and pro-inflammatory cytokines in blood samples. ELISA was used to determine the alterations in these cytokines secretion levels. We have also examined EDSS score in MS patients in two groups. RESULTS: According to the results, a significant decrease in mRNA expression levels of miR-145 (p<0.0001), miR-132 (p=0.004), miR-16 (p=0.0034), STAT1 (p=0.0002), NF-κB (p<0.0001), AP-1 (p=0.0007), IL-1ß (p=0.0017), IL-6 (p=0.017), IFN-γ (p<0.0001), CCL2 (p=0.0067), CCL5 (p=0.0034), TNF-α (p<0.0001) and also significant increase in expression levels of miRNAs targets; Sox2 (p=0.0001), sirtuin-1(p=0.0007), Foxp3 (p=0.0082), PDCD1 (p=0.003) was evident in nanocurcumin treated group compared with before treatment. The secretion levels of IFN-γ (p=0.0025), CCL2 (p=0.0029), and CCL5 (p=0.0003) were reduced dramatically in test group compared with placebo group. CONCLUSION: In conclusion, nanocurcumin may be more effective on the inflammatory features of MS. According to present results, nanocurcumin may inhibit neuroinflammation in MS patients.

Changes in Th17 cells function after nanocurcumin use to treat multiple sclerosis.

BACKGROUND: MS is a chronic inflammatory disease that causes to brain inflammation and Th17 cells are considered to be important in multiple sclerosis pathogenesis. In the current study, we aimed to identify nanocurcumin effects on Th17 cells frequency, cytokines secretion, and expression of transcription factor of patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In this study we investigated frequency of Th17 lymphocytes; the expression of transcription factor, associated cytokines and the concentration of them in 35 healthy controls, and from 25 patients at baseline and after 6 months of nanocurcumin treatment and also from 25 patients whose received placebo by flowcytometry, real-time PCR and ELISA, respectively. RESULTS: Our analysis revealed that the proportions of Th17 were increased dramatically, along with increases in the levels of IL-17A, IL-23, and RORγt expression in MS patients in compared with healthy control group. Post-treatment evaluation of the nanocurcumin group revealed a significant decrease in Th17 associated parameters such as Th17 frequency (p = 0.029), expression levels of RORγt (p < 0.0001) and IL-17 (p = 0.0044) and also secretion level of IL-17 (p = 0.0011), but IL-23 mRNA expression levels and IL-23 concentration were not influenced by nanocurcumin. However, in the placebo group there is no significant changes in these factors. CONCLUSION: Our study suggests that the increase in proportion of Th17 cells might contribute to the pathogenesis of RRMS. The results of the current work indicated that nanocurcumin is able to restore the dysregulated of Th17 cells in MS patients.