Lifetime exposure to smoking and substance abuse may be associated with late-onset multiple sclerosis: a population-based case-control study.

BACKGROUND: Late-onset multiple sclerosis (LOMS), defined as the development of MS after the age of 50, has shown a substantial surge in incidence rates and is associated with more rapid progression of disability. Besides, studies have linked tobacco smoking to a higher chance of MS progression. However, the role of smoking on the risk of developing LOMS remains unclear. This study aims to evaluate the possible association between lifetime exposure to cigarette and waterpipe smoking, drug abuse, and alcohol consumption and the risk of LOMS. METHODS: This population-based case-control study involved LOMS cases and healthy sex and age-matched controls from the general population in Tehran, Iran. The primary data for confirmed LOMS cases were obtained from the nationwide MS registry of Iran (NMSRI), while supplementary data were collected through telephone and on-site interviews. Predesigned questionnaire for multinational case-control studies of MS environmental risk factors was used to evaluate the LOMS risk factors. The study employed Likelihood ratio chi-square test to compare qualitative variables between the two groups and utilized two independent sample t-test to compare quantitative data. Adjusted odds ratio (AOR) for age along with 95% confidence intervals (CI) were calculated using matched logistic regression analysis in SPSS 23. RESULTS: Totally, 83 LOMS cases and 207 controls were included in the analysis. The female to male ratio in the cases was 1.5: 1. The mean ± SD age of 83 cases and 207 controls was 61.14 ± 5.38) and 61.51 ± 7.67 years, respectively. The mean ± SD expanded disability status scale (EDSS) score was 3.68 ± 2.1. Although the results of waterpipe exposure had no significant effect on LOMS development (P-value: 0.066), ever cigarette-smoked participants had a significantly higher risk of developing LOMS than those who never smoked (AOR: 2.57, 95% CI: 1.44-4.60). Furthermore, people with a history of smoking for more than 20 years had 3.45 times the odds of developing MS than non-smokers. Drug and alcohol abuse were both associated with LOMS in our study; of which opioids (AOR: 5.67, 95% CI: 2.05-15.7), wine (AOR: 3.30, 95% CI: 1.41-7.71), and beer (AOR: 3.12, 95% CI: 1.45-6.69) were found to pose the greatest risk of LOMS, respectively. CONCLUSION: For the first time, we identified smoking, drug, and alcohol use as potential risk factors for LOMS development. According to the global increase in cigarette smoking and alcohol use, these findings highlight the importance of conducting interventional approaches for prevention.

Waterpipe Tobacco Smoking and Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple sclerosis (MS), as an autoimmune disease of the central nervous system, has a significant burden among people worldwide. Tobacco smoking is one of the most prevalent habits of patients with different diseases including those with MS, and among the methods of use, waterpipe tobacco smoking is gaining popularity. Herein, we aimed to systematically evaluate the association between waterpipe smoking and MS. METHODS: Relevant studies were identified to be included in this systematic review and meta-analysis through a systematic search in PubMed, Scopus, Web of Science, and Embase. Studies were screened by the title/abstract and then by their full text. Extraction of data was performed for relevant studies. Odds ratios (ORs) and their 95% confidence intervals (CIs) of the association between waterpipe smoking and MS were used to pool the results observed in each study. RESULTS: After the screening, a total of five studies were included in our systematic review, comprised of 3,087 individuals, among which there were 1,135 cases with MS. Random-effect meta-analysis revealed that ever-smoking waterpipe had a significant association with MS (OR: 1.73, 95% CI: 1.38-2.17, p value <0.0001). Similarly, past waterpipe smoking was significantly higher in those with MS, compared with controls (OR: 2.17, 95% CI: 1.61-2.92, p value <0.0001). Based on the reported results, smoking both tobacco and waterpipe had an additive association with MS. Finally, no association was found between the Expanded Disability Status Scale (EDSS) and waterpipe smoking. CONCLUSION: Waterpipe as one of the common ways of tobacco smoking becoming popular has an association with MS, and even the use of waterpipe for a certain period in the lifetime has a significant correlation with MS. Further large-scale studies are needed to confirm these findings. These results could help clinicians in risk-stratifying the patients and to provide better care for the MS population.

Good manufacturing practices production of human placental derived mesenchymal stem cells for therapeutic applications: focus on multiple sclerosis.

BACKGROUND: Among neurological diseases, multiple sclerosis (MS) affects mostly young adults and can cause long-term disability. While most medications with approval from regulatory agencies are very effective in treating MS disease, they are unable to repair the tissue damage found in the central nervous system (CNS). Consequently, Cell-based therapy particularly using mesenchymal stem/stromal cells (MSCs), holds promise for neuroprotection and tissue repair in MS treatment. Furthermore, placenta-derived MSCs (PLMSCs) have shown the potential to treat MS due to their abundance, noninvasive isolation from discarded tissues, no ethical problems, anti-inflammatory, and reparative properties. Accordingly, good manufacturing practices (GMPs) plays a crucial part in clinical SCs manufacturing. The purpose of our article is to discuss GMP-grade PLMSC protocols for treating MS as well as other clinical applications. METHODS AND RESULTS: Placental tissue obtained of a healthy donor during the caesarean delivery and PLMSCs isolated by GMP standards. Flow cytometry was used to assess the expression of the CD markers CD34, CD105, CD90, and CD73 in the MSCs and the mesodermal differentiation ability was evaluated. Furthermore, Genetic evaluation of PLMSCs was done by G-banded karyotyping and revealed no chromosomal instability. In spite of the anatomical origin of the starting material, PLMSCs using this method of culture were maternal in origin. CONCLUSIONS: We hope that our protocol for clinical manufacturing of PLMSCs according to GMP standards will assist researchers in isolating MSCs from placental tissue for clinical and pre-clinical applications.

A national registry-based study of ethnic differences in people with multiple sclerosis in Iran.

OBJECTIVE: The relationship between MS and ethnicity has been understudied in the Middle East compared to the United States and Europe. As Iran as the highest prevalence of MS in the Middle East, we decided to investigate the demographic and clinical differences in people with MS (pwMS) from major ethnicities Iran. METHODS: In a cross-sectional study using data from National Multiple Sclerosis Registry in Iran. PwMS from six provinces were chosen and interviewed for determining their ethnicity. Persians (Fars), Kurds, Lurs, Azeris and Arabs with a clear ethnic background were included. Recorded data from the registry was used to compare the demographic and clinical features. RESULTS: A total of 4015 pwMS (74.2% female) were included in the study with an average age of 36.76 ± 9.68 years. Persians and Kurds had the highest percentage of pwMS in youngest and oldest age groups, respectively, with 2.9% and 5.7% (p<0.01). The highest average age of onset was seen in Persians (29.47 ± 8.89) and the lowest observed in Mazandaranis (26.82 ± 7.68, p<0.01). Azeris and Kurds had the highest proportions of pwMS diagnosed <18 and >55, at rates of 12% and 1.6%, respectively (p<0.01). There were statistically significant differences in distribution of phenotypes (p<0.01) and time to progression to secondary progressive MS (p<0.01) such that Persians had the highest rate of clinically isolated syndrome (CIS) at 19.3% and Arabs had highest rates of relapsing-remitting MS (86.2%) and secondary progressive MS (16.4%). Lurs, Azeris and Mazandaranis had significantly more patients progressing to secondary-progressive MS <5 years from diagnosis (p<0.01). There was a significant difference in number of relapses between the ethnicities (p<0.01) with Lurs having the highest proportion of participants reporting >4 relapses with 23.0% and Azeris having the highest percentage of pwMS reporting no relapse (53.0%). Kurds had the highest Expanded Disability Status Scale (EDSS) average at 2.93 ± 1.99 and Lurs had the lowest with 1.28 ± 1.25 (p<0.01). The differences in prevalence of positive family history for the whole cohort between ethnicities were significant (P=0.02), ranging from 12.8% in Kurds to 19.6% in Persians. CONCLUSION: We found Persians to have higher rates of pediatric MS and higher rates of CIS. Kurds and Lurs had higher and lower EDSS scores, respectively. Lurs and Persian had higher annual relapse rates. We also found lower rates of SPMS among Arabs and earlier progression to SPMS in Lurs, Azeris and Mazandaranis. Such differences highlight the importance of the potential role of ethnicities in diagnosis and prognosis of MS, especially considering their observation within the geographical limits of a single country.

Waterpipe and cigarette smoking and drug and alcohol consumption, and the risk of primary progressive multiple sclerosis: A population-based case-control study.

Background: Multiple sclerosis (MS) is a chronic central nervous system disease, and primary progressive multiple sclerosis (PPMS) is one the main types of MS, which has unknown environmental risk factors. The present study was conducted with the aim to identify the association of waterpipe and cigarette smoking, substance abuse, and alcohol consumption with the risk of PPMS development. Methods: A population-based, case-control study was conducted in Tehran, Iran, on 146 PPMS cases and 294 controls. PPMS cases were diagnosed and confirmed by neurologists. Standard random digit dialing was used to select sex-matched healthy control participants from the same source population as the cases. Logistic regression analysis was used to estimate unadjusted and adjusted odds ratios (OR). Results: In total, 440 subjects participated in the study. PPMS was associated with ever smoking cigarettes [OR = 2.48; confidence interval (CI) = 1.44-4.27], and passive smoking (OR = 2.20; CI = 1.34-3.62). However, having ever smoked waterpipe was not significantly associated with PPMS risk (OR = 1.19; CI = 0.62-2.26). Those who had all 3 types of smoking had an accumulative OR that was 10.45 times higher than that in individuals without any type of smoking (OR: 10.45; 95% CI = 3.5-31.2). We did not find any significant association between PPMS risk and substance abuse and alcohol consumption. Conclusion: Cigarette smoking and being exposed to passive smoking are important risk factors for developing PPMS; in addition, the use of 3 types of smoking, showed an OR higher than that in those without any smoking. Considering the global increase in tobacco smoking, this finding emphasizes the importance of interventional programs for the prevention of tobacco smoking.

Iranian specialists' approach to surgery in patients with multiple sclerosis.

Background: Data on perioperative risk stratification in patients with multiple sclerosis (MS) are limited. In this regard, the present study was conducted to investigate Iranian specialists' approach to surgical counseling for patients with MS (PwMS). Methods: 21 MS specialists were asked about 11 case scenarios with different MS disease statuses, disease-modifying therapies (DMTs), and urgency of the operation. The reasons for refusing surgery or factors that have to be considered before surgery were studied. Results: Overall, Fleiss Kappa was estimated to be 0.091 [95% confidence interval (CI): 0.090-0.093, P < 0.001] indicating a very poor level of agreement among responders. Conclusion: PwMS face surgery for various reasons. Risk assessment of surgery, the effect of various drugs such as anesthetics and DMT on patients, as well as many other aspects of MS are issues challenging the practitioners. Clarifying the various dimensions of these issues requires further research.

The effects of different types of smoking on recovery from attack in hospitalized multiple sclerosis patients.

BACKGROUND: Several studies demonstrated the association between tobacco smoking and higher risk and increased progression of multiple sclerosis (MS). Data about the effect of smoking during the recovery from MS attacks is limited. Furthermore, different types of tobacco exposures such as water pipe and passive smoking are not well assessed separately. So this study evaluated the effect of different types of smokes, cigarette and water pipe as well as passive smoking on the function recovery of relapsing-remitting MS (RRMS) attacks METHODS: This cohort study evaluated the adult patients with RRMS and Expanded Disability Status Scale (EDSS) < 5 in the attack phase. Patients were divided into two groups: smokers and non-smokers. The smokers included those who use cigarette, water pipe as well as passive smokers as subgroups for more analyses later. EDSS was monitored after relapse and two months after relapse. Change of EDSS considered as the criteria for functional recovery. The correlation between the amount of consumption and disability level was assessed among smokers by Pearson's correlation test. While, the difference of EDSS between smoker and non-smoker were assessed by Independent samples T-test. RESULTS: 142 patients were evaluated. 79 (55.6%) were smokers (43% male) while 63 (44.4%) were non-smokers (36.5% male). There was a statistically significant difference in change of EDSS between smoker and non-smoker groups, which change of EDSS was higher in non-smoker (-2.62 ± 0.90 non-smoker vs. -1.75 ± 0.76 smoker, P < 0.001). Also, only there was a significantly lesser decline in EDSS after two months in the cigarette smokers in subgroups analyses (P < 0.001). A correlation analysis revealed a significant positive correlation between the number per day of cigarette smoking and EDSS after relapse (r = 0.3, P = 0.03) and a significant positive correlation between minutes per month of smoking of water pipe and EDSS two months after relapse (r =  0.6 , P > 0.001). CONCLUSION: Tobacco smoking especially cigarette smoking is associated with a negative effect on recovery from the attack in patients with RRMS.

The Prevalence of Cancer in Patients with Multiple Sclerosis (MS) who were Under Treatment with Natalizumab (Tysabri): A Systematic Review and Meta-Analysis.

Background: To determine the pooled prevalence of cancer in subjects with multiple sclerosis (MS) who received Natalizumab. Methods: Two researchers systematically searched PubMed, Scopus, EMBASE, Web of Science, google scholar, and gray literature including references of the included studies. The search strategy which was used in PubMed was ("Disseminated Sclerosis" OR "multiple sclerosis" OR "MS" OR "Acute Fulminating") AND ("Cancer" OR "Neoplasia*" OR "Neoplasm*" OR "Tumor*" OR "Malignancy" OR "Benign Neoplasm" OR "Malignant neoplasm") AND ("Tysabri" OR "Antegren" OR "natalizumab" OR "Modifying Therapy"). Results: We found 1,993 articles by literature search, and 1,573 studies remained after removing duplicate studies. For metaanalysis, we used the extracted data of eight studies. The pooled prevalence of cancer in patients who received Natalizumab was 2% (95%CI: 1-3%; I2: 99.4%, P < 0.001). The pooled prevalence of basal cell carcinoma in patients with cancer was 12% (95%CI: 5-20%; I2:50.3%, P = 0.13). Conclusions: The main finding of this systematic review and metaanalysis is that the pooled prevalence of cancer in subjects who suffer from MS and received natalizumab was 2%.

Vascular Endothelial Growth Factor as a Predictive and Prognostic Biomarker for Multiple Sclerosis.

BACKGROUND: Growing bodies of evidence suggest that angiogenesis plays a crucial role in the development and progression of multiple sclerosis (MS). Vascular endothelial growth factor (VEGF) is one of the key factors involved in angiogenesis. Because of this importance, we investigated the serum levels of VEGF in MS patients according to their clinical phase and subtype of MS in this study. MATERIAL AND METHODS: This case-control study was done on 47 definite MS patients with the first clinical attack and 47 randomly selected individuals without any underlying inflammatory and autoimmune disease as the control group. The total serum VEGF level was measured from the subject's peripheral blood sample by ELISA during the first and second attacks of MS and 6 months after the first attack in the remission phase as well as the control group. In addition, the correlation between these variables and the influence of gender, age, and duration of the remission phase on such associations was evaluated by using the independent t test and Pearson's correlation coefficient. RESULTS: There was an increase in the serum level of VEGF in all phases of MS compared with non-MS individuals (p value <0.0001) and a significant correlation between the serum level of VEGF and the interval between first and second attacks (r = -720, p < 0.0001). A higher serum level of VEGF in the first attack leads to higher VEGF levels in the second and sixth mount of remission phases. CONCLUSION: Rise in the serum VEGF level may be involved in MS's relapsing phases and a shorter remission phase. Therefore, it could be used as a prognostic and predictive biomarker for MS disease.

Clinical characteristics, radiological features and prognostic factors of transverse myelitis following COVID-19 vaccination: A systematic review.

BACKGROUND: Since introducing COVID-19 vaccines, many neurological complications such as acute transverse myelitis have been reported in the literature. This study aims to identify the clinical characteristics, radiological findings, and prognostic factors in patients with COVID-19 vaccine-associated transverse myelitis (TM). METHODS: We systematically reviewed Scopus, Pubmed, Cochrane library, Google Scholar, and preprint databases using appropriate keywords from inception till 8th April 2022. Besides, we manually searched the reference lists of the included studies and relevant previous reviews. RESULTS: We included 28 studies identifying 31 post-COVID-19 vaccination myelitis patients (17 female and 14 male). The mean age of the included patients was 52±19 years. ChAdOx1 nCoV-19 vaccine (Oxford-AstraZeneca) was the most common type of vaccine in association with myelitis (12 out of 31), followed by Pfizer (8 out of 31), Moderna (7 out of 31), Sinopharm (3 out of 31), and Janssen vaccine (1 out of 31). The myelitis occurred in 24 and 7 patients after administering the first and second dose of the vaccine, respectively. 21 and 10 patients had good recovery (Modified Rankin Score (MRS) <3 at the follow-up) and poor recovery (MRS≥3 at the follow-up) from myelitis, respectively. Age (OR 1.09, 95%CI 1.01-1.18, pvalue 0.02), and MRS at admission (OR 17.67, 95%CI 1.46-213.76, pvalue 0.024) were two independent risk factors for poor recovery from myelitis. CONCLUSION: The patients with higher age and MRS at admission had a worse prognosis and needed timely and more aggressive therapeutic strategies.

Hotair and Malat1 Long Noncoding RNAs Regulate Bdnf Expression and Oligodendrocyte Precursor Cell Differentiation.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophins family with well-known roles in neural development, differentiation, survival, and synaptic plasticity; however, it has not been explained thoroughly how the expression of this critical gene is regulated. To reveal some aspects of Bdnf gene regulation, here it was explored whether metastasis-associated lung adenocarcinoma transcript 1 (Malat1) and HOX transcript antisense RNA (Hotair) lncRNAs play roles in the regulation of Bdnf expression level, the effect of fingolimod treatment on downstream pathways, and oligodendrocyte precursor cell (OPC) maturation. First, in rat primary glial culture, the effect of Hotair and Malat1 was investigated on Bdnf expression using downregulation by specific DNAzymes. Then, immunostaining and RT-qPCR assays were employed to assess the functions of fingolimod and lncRNAs on OPC maturation. The results demonstrated that Bdnf was significantly correlated to Hotair and Malat1 lncRNAs in glial cells. Also, a strong correlation was observed between these two lncRNAs in glial culture and isolated OPCs. Fingolimod treatment coordinated lncRNAs' role on Bdnf expression in glial cells and enhanced OPC myelination three times compared to control. Furthermore, results suggested that Malat1 may have a role in the last stages of the intrinsic oligodendrocyte (OL) myelination regardless of fingolimod treatment. As BDNF is involved in brain development, survival, and functions, understanding the regulatory mechanism behind BDNF expression leads to a better comprehension of the pathogenesis of the neurodegenerative disorder and designing more effective treatments.

The study of COVID-19 infection following vaccination in patients with multiple sclerosis.

BACKGROUND: At this time vaccination against SARS-CoV2 is a global priority. Cases with multiple sclerosis (MS) were among the first vaccinated populations in Iran. We evaluated the change in the frequency of COVID-19 after vaccination and the associated factors with severe COVID-19 infection before and after full vaccination. METHODS: A questionnaire was validated to investigate the basic characteristics (age, gender, education, body mass index, smoking status, and comorbidities), MS disease and treatment status (MS type, MS duration, The Expanded Disability Status Scale (EDSS), disease modifying treatments) and the information about COVID-19 infection and severity. RESULTS: 692 (91.9%) of participants have received both doses of vaccines, of which Sinopharm appeared to be the most common type. Significant difference of COVID-19 infection prevalence was seen before vaccination and after full vaccination (difference: 0.16, 95% CI: 0.12-0.20) (p value < 0.001). The difference was not significant for severe cases (those who were admitted in the ward or ICU) relative to the COVID-19 cases or the whole participants. Of all the basic and disease factors, only EDSS showed a significant association with severe COVID-19 before vaccination. Severe COVID-19 in fully vaccinated cases did not show any significant relation to any of basic or disease characteristics except with prior history of severe allergic reactions (OR: 17.1, p value: 0.001). DISCUSSION: The decreased frequency of infection with SARS-CoV2 was predictable but the insignificant difference in cases with the severe forms of the disease raise concern. The only significant predictor was found to be severe allergic reactions. As there are debates on antiCD20 s association with severe COVID-19 and vaccine efficacy, we could not find such significant relation. The other noticeable point about the found relation of EDSS and critical COVID-19 before vaccination is the absence of such relation after full vaccination.

Investigating the association of polymorphisms of ANKRD55 and MMEL1 with susceptibility to multiple sclerosis in Iranian population.

OBJECTIVE: Multiple sclerosis (MS) is an autoimmune neurological disability in which immune cells attack the myelin sheaths that protect nerve fibers. The pathogenesis of the disease involves both complex genetic effects as well as multifaceted gene-environment interactions. In the present study, we examined the association of two Single nucleotide polymorphisms (SNPs) in ANKRD55 (rs6859219) and MMEL (rs3748816) with MS in the Iranian population. ANKRD55 is specifically expressed in human peripheral blood mononuclear cells and CD4 + T cells, while MMEL1is involved in the degradation of both neuropeptides and ß-amyloid. METHODS: In this case-control study, 110 patients with MS and 110 matched healthy controls were enrolled. The Participants were genotyped for ANKRD55 and MMEL1 SNPs using PCR-RFLP and Real-Time TaqMan SNP Genotyping respectively. The results were finally analyzed using SPSS software version 22. RESULTS: Our results did not show significant differences in allelic frequencies of two SNPs among cases and controls (P-Value >0.05). However, for ANKRD55 (rs6859219), CA genotype was shown to have a protective effect (p = 0.035 and OR = 0.55), while CC genotype was a susceptive genotype to MS (p = 0.036 and OR = 1.8). There was no significant difference in genotypic frequencies of SNP rs3748816 in MMEL1. CONCLUSION: We could successfully replicate the association of ANKRD55 (rs6859219) with susceptibility to MS in the Iranian population. Our result can provide an insight into better understanding the pathogenesis of MS and also improve the genetic counseling for patients affected with multiple sclerosis in Iran.

Low carbohydrate diet score and odds of neuromyelitis optica spectrum disorder: A case-control study.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating inflammatory disease of The Central nervous system. We aimed to investigate the association between low carbohydrate diet (LCD) and NMOSD odds. Method: Seventy NMOSD patients with definite diagnosis and 164 hospital-based controls were enrolled in this case-control study. Dietary data was obtained using a validated 168-item food frequency questionnaire. To determine the LCD score, participants were stratified into 11 groups according to carbohydrate, protein, fat, animal fat, animal protein, vegetable fat and vegetable protein intakes. Higher intake of protein and fat, and lower intake of carbohydrate received a higher score between 0-10. Macronutrients scores were summed together and LCD scores calculated. The association between LCD scores and likelihood of being assigned to NMOSD group was investigated using multiple regression models. Results: Total LCD scores increased from the median of 21.00 in the first decile to 53.00 in the tenth decile of LCD score. After adjustment for confounding factors including age, gender, BMI, energy intake, cigarette smoking and alcohol consumption, an inverse association was detected between LCD scores and odds of NMOSD. The odds of suffering from NMOSD declined significantly about 78% (OR: 0.22; 95% CI: 0.05-0.87) and 76% (OR: 0.24; 95% CI: 0.06-0.93) in the fifth and sixth deciles of LCD score compared to the first decile. Conclusion: From the obtained results it can be speculated that higher carbohydrate and lower protein and fat intakes may be associate with the increased odds of NMOSD. However, further studies are needed to confirm these results.

Neuromyelitis optica spectrum disorder (NMOSD) associated with cancer: A systematic review.

NMOSD: is a disease shown to be highly associated with other diseases such as autoimmune diseases. There are a few reports of this association with cancer. So, this systematic review aimed to obtain a broad understanding on the cancers associated in NMOSD, including the source of common perceptions and assumptions in this regard. METHODS: in this study, we systematically searched the PubMed, EMBASE, SCOPUS, Web of Sciences, Proquest, Ovid, conference proceedings, and reference lists of the retrieved articles. All NMOSD cases who met the last version of criteria for its diagnosis, which reported the patients with a history of cancer before or after the onset of neurological symptoms without time limitations, and those who were referred as paraneoplastic neuromyelitis optica in articles published in English language (both the abstract & full text), were assessed. Finally, each study was critically appraised. RESULTS: Only 47 studies met the inclusion criteria, so they were assessed for qualitative synthesis. Considering the Euro network criteria, only 62 cases met this issue. The mean age of 52.21 ± 17.14 and 52.16 ± 17.21 was reported for cancer and NMOSD cases with female predominance (79%), respectively. The most reported organ in the cancer population were genitourinary (n = 14, 22.3%), breast (n = 12, 19.4%), lung (n = 12, 19.3%), gastrointestinal (n = 7, 11.3%), and hematology (n = 6, 9.7%), respectively. CONCLUSION: In older NMOSD patients without suspicious symptoms, we recommend paying more attention to lung, breast and genitourinary (especially ovary) cancer screening. Also, cancer resection had positive effect on the attack numbers after receiving treatment and NMOSD recovery.

Home-based exercise training influences gut bacterial levels in multiple sclerosis.

BACKGROUND: Multiple sclerosis is associated with gut microbiome alterations. The current study aimed to investigate the effect of home-based exercise on gut bacteria in people with multiple sclerosis (MS). We also examined the association of exercise-induced gut bacterial modulation with circulating levels of inflammatory and anti-inflammatory cytokines. MATERIALS AND METHODS: Forty-two people with MS (female/male: 31/11, expanded disability scale status <5) participated in this study and were divided into two groups: 6 months of home-based exercise (5 sessions per week) and controls. Before and after the intervention, the following parameters were assessed: gut microbiota, including faecalibacterium prausnitzii, akkermansia muciniphila, prevotella and bacteroides counts; cytokine levels including interleukin (IL)-10 and tumor necrosis factor-alpha (TNF-α); and psychosocial factors including anxiety, depression, and fatigue. RESULTS: Home-based exercise significantly increased prevotella counts, and decreased akkermansia muciniphila counts (p < 0.05); however, there were no significant effects on faecalibacterium prausnitzii and bacteroides counts (p > 0.05). There were no significant effects of home-based exercise on circulating cytokine levels (p > 0.05). Moreover, home-based exercise was associated with significant improvements in anxiety and depression (p < 0.05); however, fatigue revealed no significant change (p > 0.05). Akkermansia muciniphila, prevotella and bacteroides count changes in response to the intervention were correlated with changes in IL-10 (r = -0.052, r = 0.67, and r = -0.55, respectively). CONCLUSION: In general, our data revealed the effect of exercise on gut bacteria, especially prevotella, and akkermansia muciniphila counts, which can probably have a beneficial effect on MS disease pathology and course; however, the lack of changes in cytokines following exercise suggests the possible role of mechanisms other than modulation of circulating IL-10 and TNF- α levels.

The association between dietary total antioxidant capacity and NMO-IgG seropositivity in patients with neuromyelitis optica spectrum disorder.

OBJECTIVES: There is growing evidence highlighting the role of environmental risk factors of NMO-IgG seropositivity in patients with neuromyelitis optica spectrum disorder (NMOSD). The present study investigated the possible association between dietary total antioxidant capacity (TAC) and NMO-IgG seropositivity in NMOSD patients. METHODS: Fifty-six patients with a definite diagnosis of NMOSD were included in the study. Data on patients' age, gender, height, weight, cigarette smoking status, and alcohol consumption were collected and recorded. Body mass index (BMI) was also calculated. In addition, dietary habits of patients were evaluated using an adjusted semi-quantitative food frequency questionnaire (FFQ) that consists of 168 food items. Dietary TAC was calculated using the oxygen radical absorption capacity (ORAC) method. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the NMO-IgG serum status. The association between dietary TAC and odds of NMO-IgG seropositivity was measured using the logistic regression analysis. RESULTS: The mean of dietary TAC was 8362.8 (µmolTE/1000 kcal) in seronegative patients and 6609.9 (µmolTE/1000 kcal) in seropositive patients and had a significant difference between the mentioned groups of patients (P: 0.02). An inverse association was found between dietary TAC and odds of NMO-IgG seropositivity in all three regression models. The higher dietary intake of antioxidant resulted in significant findings as follows: 92% (95% CI: 0.01-0.53), 97% (95% CI: 0.00-0.34), and 97% (95% CI: 0.00-0.32) lower odds of NMO-IgG seropositivity in the fourth quartiles of the first, the second, and the third regression model, respectively. Moreover, the inverse association between fruit intake and odds of NMO-IgG seropositivity was significant in the third quartile (OR:0.10; 95%CI: 0.01-0.97). CONCLUSION: The present study indicated a significant inverse association between dietary TAC and NMO-IgG seropositivity of NMOSD patients. As no definite treatment can be offered for NMOSD and nutrition is a modifiable factor in this regard, specification of dietary factors affecting the risk of NMOSD is of great value.

RNA Sequencing of CD4+ T Cells in Relapsing-Remitting Multiple Sclerosis Patients at Relapse: Deciphering the Involvement of Novel genes and Pathways.

CD4+ T cells are known as a noteworthy potential modulator of inflammation in multiple sclerosis (MS). In the current study, we investigated the transcriptome profile of CD4+ T cells in patients with relapsing-remitting MS (RRMS) at the relapse phase. We performed RNA sequencing of CD4+ T cells isolated from four relapsing-remitting MS (RRMS) patients at the relapse phase and four age- and sex-matched healthy controls. The edgeR statistical method was employed to determine differentially expressed genes (DEGs). Gene set enrichment analysis was subsequently performed. Applying a physical interaction network, genes with higher degrees were selected as hub genes. A total of 1278 and 1034 genes were defined at significantly higher or lower levels, respectively, in CD4+ T cells of RRMS patients at the relapse phase as compared with healthy controls. The top up- and downregulated genes were JAML and KDM3A. The detected DEGs were remarkable on chromosomes 1 and 2, respectively. The DEGs were mainly enriched in the pathways "regulation of transcription, DNA-templated," "regulation of B cell receptor signaling pathway," "protein phosphorylation," "epidermal growth factor receptor signaling pathway," and "positive regulation of neurogenesis." Moreover, 16 KEGG pathways mostly associated with the immune system and viral infections were enriched. In the constructed physical interaction networks, UBA52 and TP53 were shown to be the most highly ranked hub genes among upregulated and downregulated genes, respectively. By applying global transcriptome profiling of CD4+ T cells, we deciphered the involvement of several novel genes and pathways in MS pathogenesis. The present results must be confirmed by in vivo and in vitro studies.

A focus on allogeneic mesenchymal stromal cells as a versatile therapeutic tool for treating multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system (CNS) chronic illness with autoimmune, inflammatory, and neurodegenerative effects characterized by neurological disorder and axonal loss signs due to myelin sheath autoimmune T cell attacks. Existing drugs, including disease-modifying drugs (DMD), help decrease the intensity and frequency of MS attacks, inflammatory conditions, and CNS protection from axonal damage. As they cannot improve axonal repair and show side effects, new therapeutic options are required. In this regard, due to their neuroprotection properties, immunomodulatory effects, and the ability to differentiate into neurons, the transplantation of mesenchymal stromal cells (MSCs) can be used for MS therapy. The use of adipose-derived MSCs (AdMSCs) or autologous bone marrow MSCs (BMSCs) has demonstrated unexpected effects including the invasive and painful isolation method, inadequate amounts of bone marrow (BM) stem cells, the anti-inflammatory impact reduction of AdMSCs that are isolated from fat patients, and the cell number and differentiation potential decrease with an increase in the age of BMSCs donor. Researchers have been trying to search for alternate tissue sources for MSCs, especially fetal annexes, which could offer a novel therapeutic choice for MS therapy due to the limitation of low cell yield and invasive collection methods of autologous MSCs. The transplantation of MSCs for MS treatment is discussed in this review. Finally, it is suggested that allogeneic sources of MSCs are an appealing alternative to autologous MSCs and could hence be a potential novel solution to MS therapy.