The effects of probiotics supplementation on serum markers of oxidative stress in relapsing-remitting multiple sclerosis: a randomised, double-blind, placebo-controlled clinical trial.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation and demyelination of the central nervous system. Probiotics, through the gut-brain axis, are suggested to enhance clinical outcomes in patients with MS. This study scrutinizes the effects of probiotic supplementation in relapsing-remitting MS (RRMS) patients. Methods: In this parallel, randomized, double-blind, placebo-controlled trial, 90 RRMS patients, with Expanded Disability Status Scale (EDSS) < 4, received either the probiotic (Lactocare®) or a placebo twice daily for four months. Assessed outcomes included level of disability (based on EDSS), cognitive function (Symbol Digit Modalities Test [SDMT], three-second version of Paced Auditory Serial Addition Test [PASAT-3]), depressive symptoms (Beck Depression Inventory- II [BDI-II]), and manual dexterity (Nine-Hole Peg Test [9HPT]). Blinding was performed for outcome assessors and the patients. All assessments were conducted at baseline and after four months, and the findings compared between the groups of the study. Results: Out of 90 randomized patients, 60 completed the trial (29 in the probiotics group, 31 in the placebo group). Probiotics supplementation was not associated with significant improvement in EDSS, BDI-II, PASAT, SDMT, and non-dominant hand 9HPT (p-values > 0.05). Intragroup improvements in PASAT-3 (change median: 2 [IQR:9.5]) and dominant hand 9HPT (change median: -0.43 [IQR: 2.15]) were observed in the probiotic supplementation group, which was comparable to placebo. Conclusion: Supplementation with a seven-strain probiotics product for four months does not result in a significant improvement in depressive symptoms, cognitive performance, level of disability, and manual dexterity of RRMS patients with EDSS < 4.

Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis

Unveiling oxidative stress in multiple sclerosis phenotypes: Exclusion of confounding variables for accurate correlation with disability status.

Circulatory antioxidant and oxidative stress markers are in correlation with demographics but not cognitive functions in multiple sclerosis patients

Oxidative stress is recognized as a key pathological mechanism in multiple sclerosis (MS), and fatigue is one of the most prevalent and disabling symptoms. In this cross-sectional study, 85 patients diagnosed with relapsing-remitting MS (RRMS) and Expanded Disability Status Scale (EDSS) < 4.5 were recruited. Fatigue was evaluated by the Comprehensive Fatigue Assessment battery MS (CFAB-MS), which also assesses fatigue-related factors. Venous blood samples were collected to measure levels of glutathione peroxidase (GPX), catalase (CAT), malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD). Most correlations between oxidative stress markers and fatigue measures were not statistically significant. However, MDA levels showed significant positive correlations with Visual Analog Scale (VAS) scores for sleep problems (r:0.23, p-value:0.04); Walking problems VAS (r:0.31, p-value < 0.01); anxiety and worry (r:0.22, p-value < 0.05); and significant negative correlations with mood (r:-0.21, p-value < 0.05) and fatigue management (r:-0.22, p-value:0.04). Additionally, GSH levels were positively correlated with Fatigue VAS (r:0.24, p-value:0.02) and CAT was negatively correlated with stress VAS (r:-0.21, p-value:0.04). After applying the Benjamini-Hochberg correction, none of the correlations remained statistically significant. At an exploratory level, this study suggests that there is a minimal association between oxidative stress, fatigue and its related factors in minimally disabled RRMS patients.

Chronic glaucoma is a multifactorial disease among which oxidative stress may play a major pathophysiological role. We conducted a systematic review and meta-analysis to evaluate the levels of oxidative and antioxidative stress markers in chronic glaucoma compared with a control group. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies reporting oxidative and antioxidative stress markers in chronic glaucoma and in healthy controls using the following keywords: “oxidative stress” or “oxidant stress” or “nitrative stress” or “oxidative damage” or “nitrative damage” or “antioxidative stress” or “antioxidant stress” or “antinitrative stress” and “glaucoma”. We stratified our meta-analysis on the type of biomarkers, the type of glaucoma, and the origin of the sample (serum or aqueous humor). We included 22 case-control studies with a total of 2913 patients: 1614 with glaucoma and 1319 healthy controls. We included 12 studies in the meta-analysis on oxidative stress markers and 19 on antioxidative stress markers. We demonstrated an overall increase in oxidative stress markers in glaucoma (effect size = 1.64; 95%CI 1.20–2.09), ranging from an effect size of 1.29 in serum (95%CI 0.84–1.74) to 2.62 in aqueous humor (95%CI 1.60–3.65). Despite a decrease in antioxidative stress marker in serum (effect size = –0.41; 95%CI –0.72 to –0.11), some increased in aqueous humor (superoxide dismutase, effect size = 3.53; 95%CI 1.20–5.85 and glutathione peroxidase, effect size = 6.60; 95%CI 3.88–9.31). The differences in the serum levels of oxidative stress markers between glaucoma patients and controls were significantly higher in primary open angle glaucoma vs primary angle closed glaucoma (effect size = 12.7; 95%CI 8.78–16.6, P < 0.001), and higher in pseudo-exfoliative glaucoma vs primary angle closed glaucoma (effect size = 12.2; 95%CI 8.96–15.5, P < 0.001). In conclusion, oxidative stress increased in glaucoma, both in serum and aqueous humor. Malonyldialdehyde seemed the best biomarkers of oxidative stress in serum. The increase of some antioxidant markers could be a protective response of the eye against oxidative stress.

To compare the levels of serum prolidase activity and oxidative stress markers, including total oxidative status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and total free sulfhydryl (-SH) in healthy pregnant women and pregnant women with intrauterine growth restricted infants. Serum samples were obtained from 18 healthy third trimester pregnancies and 14 pregnancies complicated by fetal growth restriction (FGR). The criteria for FGR were clinical evidence of suboptimal growth, ultrasonographic demonstration of deviation from normal percentiles of growth, and birthweight under the 10th percentile. We spectrophotometrically measured serum prolidase activity, TAC, TOS, and -SH levels. Oxidative stress was determined from total antioxidant capacity and total oxidant status measurement and calculation of the oxidative stress index. Serum TAC and -SH levels were significantly lower in the FGR group than in the healthy control group (P = 0.001, P < 0.001, respectively), whereas TOS level, OSI value, and prolidase activity were significantly higher (P = 0.003, P < 0.001, P < 0.001, respectively). Prolidase activity was positively correlated with TOS and OSI values (rho = 0.552, P = 0.041 and rho = 0.635, P = 0.015, respectively) and negatively correlated with TAC and -SH levels (rho = -0.578, P = 0.030 and rho = -0.622, P = 0.018, respectively). The present study shows that serum prolidase activity and oxidative stress are significantly associated with the presence of FGR and that the correlation between serum prolidase activity and markers of oxidative stress are represented as increased serum TOS level and decreased serum TAC and -SH levels, suggesting an association of collagen turnover and oxidative stress in vascular dysfunction.

Diagnostic Potential of Autophagy-5 Protein, Apolipoprotein B-48, and Oxidative Stress Markers in Serum of Patients with Early-Stage Ischemic Stroke

Background: Multiple sclerosis (MS) is a demyelination disorder of the central nervous system (CNS), which is believed to be associated with oxidative stress.Therefore, researchers try to find reliable biomarkers to monitor the disease and predict its prognosis.Cholesterol and lipids in the myelin sheath are vital for nerve cells.Serum lowdensity lipoprotein (LDL) is susceptible to lipid peroxidation induced by oxidative stress.This study aimed to evaluate oxidative stress markers in the serum of patients with relapsing-remitting MS (RRMS) and examine their correlation with lipid markers.Methods: A total of 18 MS patients (14 women and 4 men) and 18 healthy subjects (matched by age and sex) were enrolled in this cross-sectional study.The serum samples were collected in both relapsing and remitting phases.The prooxidant-antioxidant balance (PAB), malondialdehyde (MDA), and oxidized LDL (oxLDL) were measured as markers of oxidative stress. Results:The mean age of participants was 29.21 (22-42) years.In the comparison between the patient and control groups, the most differences were increased levels of PAB in the patient group (P < 0.05), no difference between relapsing and remitting phases (P = 0.995), increased MDA levels in the relapsing phase (P = 0.013)--but no change in the remitting phase (P = 0.068), no difference in LDL and oxLDL levels in the patient group (P > 0.05), and MDA, LDL, and oxLDL levels did not have any significant correlation with PAB (P > 0.05). Conclusion:High levels of oxidative stress markers were present in both phases of the disease.Lipid peroxidation markers (such as MDA) increased in the acute phase, but oxLDL did not change.Also, there was no significant correlation between oxidative stress and cholesterol markers.

Probiotics may have a promising role in chronic autoinflammatory diseases. The current systematic review and meta-analysis investigated the effects of probiotics on disease progression, depression, general health, and anthropometric measurements in Relapsing-Remitting Multiple Sclerosis (RRMS) patients. The English literature search was performed using PubMed, Scopus, Web of Science, and the Central Cochrane Library through January 2021. Random effect models were used to synthesise quantitative data by STATA14 . From a total of 152 identified entries, four trials were included in quantitative synthesis (n=213; 106 as intervention, 107 as control). An additional six studies with the same structure and different markers were also systematically reviewed. The pooled effect size showed that Expanded Disability Status Scale (EDSS) (WMD=-0.43; 95% CI=-0.65, -0.20; P<.001), Beck Depression Inventory-Ⅱ (BDI-Ⅱ) (WMD=-3.22; 95% CI=-4.38, -2.06; P<.001) and General Health Questionnaire (GHQ) (WMD=-4.37; 95% CI=-6.43, -2.31; P<.001) were improved following probiotics supplementation. However, body weight and body mass index did not statistically change. Our findings revealed that probiotics supplementation can improve disease progression, suppress depression, and general health in MS patients; although, further investigations may be needed.

This is the first study in Iraq to integrate socioeconomic, genetic, and oxidative stress markers in MS patients, revealing unique associations between HLA-DRB1 polymorphisms and relapsing-remitting MS (RRMS). This work investigated the demographic, clinical, oxidative stress, and molecular aspects influencing quality of life in multiple sclerosis patients in Sulaymaniyah, Iraq. A cross-sectional study was undertaken with 63 MS patients and 20 healthy controls to evaluate quality of life using the Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaire. We compiled demographic and clinical information, including age, sex, educational level, socioeconomic level, multiple sclerosis phenotype, disease duration, and Expanded Disability Status Scale (EDSS) scores. In this work, single nucleotide polymorphism (SNP) of HLA-DRB1 was investigated in conjunction with oxidative stress markers, including MDA, 8-OHdG, and GPx activity, to the expression of the NRF2 gene. Significant relationships (p < 0.05) between quality of life and crucial variables, including the degree of the disease, level of education, socioeconomic level, and oxidative stress markers, were revealed by statistical analysis. MDA and 8-OHdG levels tightly predicted NRF2 expression (R2 = 0.713, p < 0.001 according to regression analysis). This result draws attention to an antioxidant response seeking to offset its lack of potency. All MS subtypes showed noticeably higher NRF2 expression than controls, according to post hoc analysis.PPMS showed the highest overexpression (p < 0.001). The results indicated the importance of oxidative stress markers in multiple sclerosis and how it affects quality of life. For this reason, personalized treatments must target both oxidative stress and socioeconomic status to help patients get better, especially in underdeveloped areas. Besides this, the study offers important information for legislators and medical practitioners creating thorough, patient-centered care plans to improve MS management. Furthermore, serum vitamin D3 levels varied greatly among MS subtypes (p = 0.008); PPMS patients had the lowest levels. Though p = 0.162, vitamin B12 levels did not approach statistical relevance; lower levels were observed in progressive MS forms, implying a possible function in disease pathogenesis. In this work, single nucleotide polymorphism (SNP) of HLA-DRB1 has been investigated together with oxidative stress markers including MDA, 8-OHdG, and GPx activity to NRF2 gene expression. Two RRMS patients showed the T risk allele (G > A transition at rs3135), indicating a possible genetic predisposition to MS in this cohort based on SNP analysis. Moreover, MS patients and healthy controls underwent genotyping analysis utilizing Sanger sequencing to evaluate the distribution of HLA-DRB1 rs3135388. More often detected in MS subtypes, especially in RRMS forms, the T allele supports a genetic susceptibility connected to oxidative stress dysregulation.

BackgroundDefining the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) can be challenging and delayed. A digital tool (MSProDiscuss) was developed to facilitate physician-patient discussion in evaluating early, subtle signs of multiple sclerosis (MS) disease progression representing this transition.ObjectiveThis study aimed to determine cut-off values and corresponding sensitivity and specificity for predefined scoring algorithms, with or without including Expanded Disability Status Scale (EDSS) scores, to differentiate between RRMS and SPMS patients and to evaluate psychometric properties.MethodsExperienced neurologists completed the tool for patients with confirmed RRMS or SPMS and those suspected to be transitioning to SPMS. In addition to age and EDSS score, each patient’s current disease status (disease activity, symptoms, and its impacts on daily life) was collected while completing the draft tool. Receiver operating characteristic (ROC) curves determined optimal cut-off values (sensitivity and specificity) for the classification of RRMS and SPMS.ResultsTwenty neurologists completed the draft tool for 198 patients. Mean scores for patients with RRMS (n=89), transitioning to SPMS (n=47), and SPMS (n=62) were 38.1 (SD 12.5), 55.2 (SD 11.1), and 69.6 (SD 12.0), respectively (P<.001, each between-groups comparison). Area under the ROC curve (AUC) including and excluding EDSS were for RRMS (including) AUC 0.91, 95% CI 0.87-0.95, RRMS (excluding) AUC 0.88, 95% CI 0.84-0.93, SPMS (including) AUC 0.91, 95% CI 0.86-0.95, and SPMS (excluding) AUC 0.86, 95% CI 0.81-0.91. In the algorithm with EDSS, the optimal cut-off values were ≤51.6 for RRMS patients (sensitivity=0.83; specificity=0.82) and ≥58.9 for SPMS patients (sensitivity=0.82; specificity=0.84). The optimal cut-offs without EDSS were ≤46.3 and ≥57.8 and resulted in similar high sensitivity and specificity (0.76-0.86). The draft tool showed excellent interrater reliability (intraclass correlation coefficient=.95).ConclusionsThe MSProDiscuss tool differentiated RRMS patients from SPMS patients with high sensitivity and specificity. In clinical practice, it may be a useful tool to evaluate early, subtle signs of MS disease progression indicating the evolution of RRMS to SPMS. MSProDiscuss will help assess the current level of progression in an individual patient and facilitate a more informed physician-patient discussion.

Introduction: Brain-derived neurotrophic factor (BDNF) levels are reduced in advanced stages of multiple sclerosis (MS) and may be associated with reduced regenerative capability in progressive MS. This has brought increased attention to factors regulating BDNF production in MS. Our aim was to investigate the link between neurotrophin-regulating microRNAs (miRNA) and disease progression in MS. Materials and Methods: Serum levels of BDNF and peripheral blood mononuclear cell (PBMC) expression levels of miR-132-3p, miR-106b-5p and miR-19b-3p were respectively measured by ELISA and real time PCR in twelve relapsing remitting MS (RRMS) patients, seven secondary progressive MS (SPMS) patients and fourteen healthy controls. Results: Serum BDNF levels were significantly reduced in SPMS patients, while selected miRNAs were significantly upregulated in PBMC of RRMS and SPMS patients. miR-106b-5p and miR-19b-3p respectively showed the highest sensitivity and specificity for MS diagnosis by receiver operating characteristic curve analysis. There was a negative correlation between levels of BDNF and the miRNAs in RRMS. Likewise, levels of BDNF and the investigated miRNAs showed positive and negative correlations respectively with the expanded disability status scale in RRMS and SPMS patients. miR-132-3p and miR-106b-5p levels showed positive correlations with the progression index in SPMS patients. Conclusion: Our results suggest that increased disability is associated with downregulation of miR-132-3p, miR-106b-5p and miR-19b-3p in RRMS patients and putatively promotes increased production of neuroprotective BDNF as a compensatory mechanism. This link between the investigated miRNAs and BDNF in RRMS does not appears to hold for SPMS. This might be one of the factors contributing to reduced regenerative ability in the progressive stage of MS.

Infertility is a common cause of marital disharmony in Nigeria because of the high premium placed on child bearing. Male factor is a significant contributor and declining male fertility rate has been observed over the past decade. Oxidative stress has been implicated in the aetiology of male infertility. The objective of the study was to compare the serum levels of oxidative stress markers (TAC – Total Antioxidant Capacity, MDA - Malondialdehyde and SOD – Superoxide dismutase) in male partners of fertile and infertile couples. This was a case controlled study carried out over a period of 8 months on male partners of infertile couple. Thirty-six were male partners of fertile couple with normal semen parameters and no history of infertility while 73 were male partners of infertile couple which consists of 28 males with oligospermia, 28 with oligoasthenospermia and 17 with asthenospermia.. Serum markers of oxidative stress (TAC, MDA and SOD) were evaluated and compared among the group. The male partners of infertile couple showed significantly low levels of TAC (P = 0.000), SOD (P = 0.000) and significantly high levels of MDA (P = 0.000) when compared with male partners of fertile couple (750.93±146.37 versus 1269.20±330.79, 11.22±3.33 versus 13.96±1.38 and 2.48±1.20 versus 1.51±0.19). Oxidative stress may be a major contributor to male infertility. Its assay may be of importance in prevention and treatment of male infertility.

Fatigue is a prominent and disabling symptom of multiple sclerosis (MS), impairing quality of life. The disease course of relapsing remitting MS (RRMS) is individual. We aimed to study the effects of demographic and clinical characteristics, as well as lifestyle risk factors on experienced fatigue and health-related quality of life (HRQoL) among RRMS patients, comparing benign and severe disease types. Altogether 198 Finnish RRMS patients were recruited for this real-life cross-sectional study. Self-reported questionnaires were used to evaluate fatigue and HRQoL by using Fatigue Scale for Motor and Cognitive Functions and 15D health-related quality of life questionnaires. Patients were categorized into subgroups based on the current disability status measured by the Expanded Disability Status Scale (EDSS) cut-off value of 4.5, and by retrospective clinical course divided into benign and aggressive RRMS. All in all, 73% of the RRMS patients suffered from fatigue. Lower HRQoL had a strong correlation with more prominent fatigue (r=-0.719). Higher EDSS was associated with more prominent fatigue and lower HRQoL in the whole RRMS cohort. Older age at the disease onset was associated with more prominent fatigue and decreased HRQoL in the groups of aggressive RRMS and EDSS > 4.5. In the groups of EDSS ≤ 4.5 and benign RRMS, a higher number of used disease-modifying treatments (DMTs) was associated with more pronounced fatigue and reduced HRQoL. In addition, higher BMI was associated with lower HRQoL in patients with benign RRMS. Side effects (45 %) and lack of efficacy (26 %) were the most common reasons for discontinuing a DMT. Cessation due to side effects was the only reason that was significantly associated with more prominent fatigue and lower HRQoL. Use of nicotine products, gender, or disease duration were not associated with fatigue or HRQoL. Individuals with severe RRMS and higher EDSS scores are more prone to experience fatigue and lower HRQoL. In addition, fatigue and lower HRQoL are more commonly observed among RRMS patients with older age at disease onset and in those with multiple DMT switches.