No abstract

Background In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls. Method We performed an online search via PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library till September 2021 to identify original studies on IL-6 and TNF-α changes after acute and regular exercise in PwMS and controls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 original studies were included in the meta-analysis. Sensitivity analyses were used to identify the origins of heterogeneity. R 4.0.4 was used to perform the meta-analysis of IL-6 and TNF-α levels before and after acute and regular exercise in PwMS, compared to controls. This study does not qualify for a clinical trial number. Results IL-6 levels did neither increase nor decrease after acute and regular exercise in PwMS, and compared to controls (pre- vs. post-intervention: Standardized Mean Difference (SMD) -0.09, 95% CI [−0.29; 0.11], p-value = 0.37, PwMS vs. Control: SMD −0.08, 95% CI [−0.33; 0.16], p-value = 0.47). In PwMS, TNF-α levels decreased after regular exercise and when TNF-α levels of both acute and regular exercise were pooled (pre- vs. post-intervention: SMD −0.51, 95% CI [-0.91; 0.11], p-value = 0.01, PwMS vs. Control: SMD −0.23, 95% CI [−0.66; 0.18], p-value = 0.26). TNF-α levels did neither increase nor decrease after acute and regular exercise in PwMS, when compared to controls. Conclusion This systematic review and meta-analysis show that exercise does not lead to significant changes in peripheral levels of IL-6 in PwMS in contrast to the observed response in healthy subjects and other medical contexts. However, regular exercise had a specific anti-inflammatory effect on blood TNF-α levels in PwMS. It remains to be investigated why PwMS display this different exercise-induced pattern of cytokines.

Background Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of neurodegenerative diseases. It has also been hypothesized that plasma exosomal lncRNAs may be used as Alzheimer’s disease (AD) biomarkers. In this systematic review, we compiled all studies on the subject to evaluate the accuracy of lncRNAs in identifying AD cases through meta-analysis. Methods A PRISMA-compliant systematic search was conducted in PubMed/MEDLINE, EMBASE, and Web of Science databases for English publications till September 2022. We included all observational studies published which investigated the sensitivity and specificity of various lncRNAs in plasma samples of AD diagnosis. Our search strategy included lncRNA and all the related spelling and abbreviation variations combined with the keyword Alzheimer’s disease. Methodological quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-II) tool. The meta-analysis was carried out using the area under the Receiver Operator Characteristic (ROC) curves (AUC) and sensitivity and specificity values to assess the accuracy of the identified lncRNAs in AD diagnosis. To account for the predicted heterogeneity of the study, a random-effects model was used. All the statistical analyses and visualizations were conducted using Stata 17.0 software. Results A total of seven studies (AD patients = 553, healthy controls = 513) were included in the meta-analysis. Three lncRNAs were upregulated (RNA BACE-AS1, RNA NEAT1, RNA GAS5), and one lncRNA (MALAT1) was downregulated in plasma samples of AD patients. RNA 51A and RNA BC200 were reported to have variable expression patterns. A lncRNA (RNA 17A) was not significantly different between AD and control groups. The pooled sensitivity, specificity, and AUC values of lncRNAs in identifying AD were (0.74; 95% CI [0.63, 0.82], I2 = 79.2%), (0.88; 95% CI [0.75, 0.94], I2 = 88.9%), and 0.86; 95% CI [0.82, 0.88], respectively. In addition, the pooled diagnostic odds ratio (DOR) of the five individual lncRNAs in AD diagnosis was 20. Conclusion lncRNAs had high accuracy in identifying AD and must be seen as a promising diagnostic biomarker of the disease.