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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.
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Exossomos , Herpesvirus Humano 4 , MicroRNAs , Esclerose Múltipla Recidivante-Remitente , Humanos , Exossomos/metabolismo , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/virologia , Herpesvirus Humano 4/genética , Feminino , Masculino , MicroRNAs/líquido cefalorraquidiano , MicroRNAs/genética , Adulto , Citocinas/líquido cefalorraquidiano , Infecções por Vírus Epstein-Barr/líquido cefalorraquidiano , Infecções por Vírus Epstein-Barr/virologia , RNA Viral/líquido cefalorraquidiano , RNA Viral/genética , Pessoa de Meia-Idade , Interferon gama/líquido cefalorraquidianoRESUMO
BACKGROUND: Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. DISCUSSION: In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. SUMMARY: These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient.
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Jejum/efeitos adversos , Jejum/fisiologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Animais , Progressão da Doença , Fadiga/diagnóstico , Fadiga/epidemiologia , Fadiga/fisiopatologia , Humanos , Esclerose Múltipla/fisiopatologiaRESUMO
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.
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Exossomos , Esclerose Múltipla , Transdução de Sinais , Humanos , Exossomos/metabolismo , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Esclerose Múltipla/terapia , Animais , MicroRNAs/metabolismo , MicroRNAs/genéticaRESUMO
BACKGROUND: There is supportive evidence that multiple sclerosis (MS) could potentially affect the peripheral nervous system. We assessed peripheral sensory and motor nerve involvement in patients with MS by a nerve conduction velocity test. METHODS: We studied 75 patients who had a relapsing-remitting or secondary progressive pattern. We measured amplitude, latency, conduction velocity, Hoffmann reflex (H-Reflex), and F-Waves. RESULTS: The amplitude of the right tibial, right proneal, left tibial, left proneal, and left median motor nerves was less than the mean for the normal population. Right ulnar sensory conduction in the patients showed an amplitude that was less than that of the normal population; there was no significant change in the amplitude of other sensory nerves. Latencies of the right and left median and right proneal motor nerves and left ulnar sensory nerves were statistically less than that of the normal population. Mean motor conduction velocity and F-wave conduction did not differ significantly from the normal population. H-reflex latencies of the right and left lower limbs were significantly more prolonged than those of the normal population. CONCLUSION: Our results suggest possible peripheral motor nerve abnormalities in MS patients, especially with the amplitude of the motor nerves; however, our results do not demonstrate any significant difference among the nerve conduction velocity parameters of sensory nerves between MS patients and the normal population.
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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.
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Esclerose Múltipla , Probióticos , Humanos , Adulto , Esclerose Múltipla/tratamento farmacológico , Qualidade de Vida , Probióticos/uso terapêutico , Suplementos Nutricionais , Fadiga , Método Duplo-CegoRESUMO
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.
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Exossomos , MicroRNAs , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , MicroRNAs/metabolismo , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Exossomos/metabolismo , Esclerose Múltipla/metabolismo , BiomarcadoresRESUMO
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.
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Disfunção Cognitiva , Resistência à Insulina , Insulinas , Esclerose Múltipla , Doenças Neurodegenerativas , Humanos , Esclerose Múltipla/complicações , Estudos Transversais , Disfunção Cognitiva/etiologia , Cognição , Testes NeuropsicológicosRESUMO
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.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Depressão , Acetato de Glatiramer/uso terapêutico , Irã (Geográfico) , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/patologia , Estudos Prospectivos , Qualidade de VidaRESUMO
BACKGROUND: Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. METHODS: This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". RESULTS: Twenty one patients (70%) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7%( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (-2.06 -0.02), p = 0.054). CONCLUSIONS: Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients' quality of life. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT01049295).
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Antineoplásicos Fitogênicos/efeitos adversos , Ácidos Graxos Ômega-3/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Adulto , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacocinética , Feminino , Humanos , Pessoa de Meia-Idade , Condução Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/farmacocinética , Paclitaxel/uso terapêutico , Resultado do TratamentoRESUMO
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.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Fumarato de Dimetilo/farmacologia , Humanos , Leucócitos Mononucleares/metabolismo , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/genética , Análise de Sequência de RNARESUMO
OBJECTIVE: To study the potential effect of Methotrexate (MTX) on lipid peroxidation and activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) two important endogenous anti-oxidant enzymes. METHODS: Twenty healthy male Newzland rabbits weighting 1500-1800 g were divided into two groups. One group was considered as the MTX groups and the other was considered as control group. Rabbits had free access to food and tap water. Rabbits in MTX group received a single dose of MTX, 20 mg/kg intraperitoneally, a similar volume of saline was administered to control group. After 6 days rabbits were uteinized and spinal tissue excised for biochemical studies. RESULTS: GPX and SOD activities in spinal tissue in rabbits of MTX group significantly reduced after MTX administration compared to control group(P = 0.002 vs 0.18). An increase in the tissue MDA level was seen in the MTX group, suggesting increased lipid peroxidation. Levels of MDA were significantly higher in MTX group compared to control group (P = 0.002). CONCLUSION: Our data suggests that MTX treatment induces oxidative tissue damage on the spinal tissue, as assessed by increased lipid peroxidation and decreased GPX and SOD levels, so decreasing oxidative stress by anti-oxidant agents may play a key role in attenuating spinal cord injury.
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Antimetabólitos Antineoplásicos/farmacologia , Glutationa Peroxidase/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Metotrexato/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Superóxido Dismutase/efeitos dos fármacos , Animais , Antimetabólitos Antineoplásicos/metabolismo , Antimetabólitos Antineoplásicos/toxicidade , Antioxidantes/metabolismo , Sequestradores de Radicais Livres/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Metotrexato/metabolismo , Metotrexato/toxicidade , Coelhos , Medula Espinal/metabolismo , Superóxido Dismutase/metabolismoRESUMO
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.
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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.
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Resistência a Medicamentos/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/genética , Adulto , Feminino , Genótipo , Humanos , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.
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RNA Helicases DEAD-box/genética , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , RNA Longo não Codificante/genética , Adulto , Estudos de Casos e Controles , Fumarato de Dimetilo/uso terapêutico , Feminino , Cloridrato de Fingolimode/uso terapêutico , Acetato de Glatiramer/uso terapêutico , Humanos , Interferon beta-1a/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto JovemRESUMO
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.
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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.
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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.
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Esclerose Múltipla , Fator de Transcrição STAT3 , Epigênese Genética , Humanos , Esclerose Múltipla/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismoRESUMO
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.
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MicroRNAs , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Interferon beta/uso terapêutico , MicroRNAs/genética , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/genética , RecidivaRESUMO
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.
Assuntos
Saúde Mental , Esclerose Múltipla/terapia , Estresse Oxidativo , Probióticos/administração & dosagem , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Saccharomyces boulardii , Adolescente , Adulto , Proteína C-Reativa/análise , Suplementos Nutricionais , Método Duplo-Cego , Fadiga/prevenção & controle , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/psicologia , Avaliação de Resultados em Cuidados de Saúde , Dor/prevenção & controle , Estudos Prospectivos , Adulto JovemRESUMO
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.