Dysregulated Network of miRNAs Involved in the Pathogenesis of Multiple Sclerosis

Dolati, Sanam; Marofi, Faroogh; Babaloo, Zohreh; Aghebati‐Maleki, Leili; Roshangar, Leila; Ahmadi, Majid; Rikhtegar, Reza; Yousefi, Mehdi

doi:10.1016/j.biopha.2018.05.050

Cited by 52 publications

(45 citation statements)

References 97 publications

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“…For this purpose, the dose of 80 mg/kg of nanocurcumin was used for 4 months in 12 patients with active AS and the frequency of Treg cells, the associated miRNAs, and cytokines expressions were measured in these patients before and after treatment. 23 The analysis of our PCR results indicated that the expression of the two miRNAs (miR-17 and miR-27) was reduced while miR-146a was significantly increased in AS patients after nanocurcumin therapy. 1 In the current study, flow cytometric analysis of PB in AS patients exhibited that daily nanocurcumin treatment for 4 months could significantly increase the percentage of PB Treg cells compared with those receiving placebo.…”

Section: Discussionmentioning

confidence: 80%

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial

Ahmadi

Hajialilo

Eghbal‐Fard

et al. 2019

J of Cellular Biochemistry

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Aim Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients. Methods Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR‐27, miR‐17, and miR‐146a) and cytokines including Interleukin‐10 (IL‐10), TGF‐β, and IL‐6 were assessed by real‐time polymerase chain reaction. Furthermore, enzyme‐linked immunosorbent assay was done to determine the secretion levels of cytokines. Results After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT‐PCR data indicated that the expression of miR‐17 and miR‐27 were significantly decreased following nanocurcumin treatment while miR‐146a and FoxP3 were significantly increased. Moreover, nanocurcumin‐treated group had high levels of IL‐10 and TGF‐β and low levels of IL‐6 production than control group. Conclusion The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.

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Section: Discussionmentioning

confidence: 80%

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial

Ahmadi

Hajialilo

Eghbal‐Fard

et al. 2019

J of Cellular Biochemistry

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“…The CSF miRNA profile parallels the extent of intrathecal inflammation, but is not specific to MS Although studies on CSF miRNAs in MS are sparse, several miRNAs identified in this study were previously described by other groups either in the CSF or other sample types. 4 Our work emphasizes, however, the predominance of CSF miRNA dysregulation in MS, in concordance with its pathogenesis. Furthermore, our results highlight the partially overlapping profile of CSF-upregulated miRNAs in infectious and inflammatory CNS disorders compared with relapsing MS.…”

Section: Csf-predominant Mirna Dysregulation and Mirna Species Newly mentioning

confidence: 66%

“…2 Several miRNAs have been associated with MS, but only few were linked to disease activity. 3,4 Most studies were performed in small cohorts, in single biological compartments, rarely compared with other neurologic disorders or were not replicated, hence large heterogeneity between study populations and analysis methods. Few studies have focused on CSF miRNAs, 5 although these might be more relevant to understanding disease regulation.…”

Section: Discussionmentioning

confidence: 99%

CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

Perdaens

Dang

D’Auria

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo perform a comprehensive multicompartment analysis of microRNA (miRNA) expression in multiple sclerosis (MS) linked to disease activity and compared with other neuroinflammatory diseases through a retrospective cross-sectional study.MethodsOne hundred twenty-seven miRNAs were measured by PCR arrays on pooled CSF, serum, and peripheral blood mononuclear cell (PBMC) samples of 10 patients with relapsing MS and 10 controls. Sixty-four miRNAs were then measured by quantitative PCR on individual CSF samples of patients with relapsing or remitting MS and controls (n = 68). Fifty-seven miRNAs were analyzed in the CSF from a second cohort (n = 75), including patients with MS, neuroinfectious, or neuroinflammatory diseases and controls. MiRNAs significantly dysregulated in the CSF were analyzed on individual serum/PBMC samples (n = 59/48) of patients with relapsing or remitting MS and controls. Post hoc analysis consisted of principal component analysis (PCA), gene set, and pathway enrichment analysis.ResultsTwenty-one miRNAs were differentially expressed, mainly upregulated in the CSF during MS relapses. Relapsing MS and neuroinfectious/inflammatory diseases exhibited a partially overlapping CSF miRNA expression profile. Besides confirming the association of miR-146a-5p/150-5p/155-5p with MS, 7 miRNAs uncharacterized for MS emerged (miR-15a-3p/124-5p/149-3p/29c-3p/33a-3p/34c-5p/297). PCA showed that distinct miRNA sets segregated MS from controls and relapse from remission. In silico analysis predicted the involvement of these miRNAs in cell cycle, immunoregulation, and neurogenesis, but also revealed that the signaling pathway pattern of remitting MS is more akin to controls rather than patients with relapsing MS.ConclusionsThis study highlights the CSF-predominant dysregulation of miRNAs in MS by identifying a signature of disease activity and intrathecal inflammation among neuroinflammatory disorders.

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“…The diagnostic ability of miRNAs in previous studies remains controversial. Significant miRNA expression variations have been detected in MS patients and related animal models, mainly in inflammatory cells (30,31), the predictive effect of each miRNA for MS is different. In particular, miR-125a-5p in the blood distinguishes MS patients from healthy controls with high specificity of 85% but low sensitivity of 56%, inversely, miR-25a-3p has sensitivity of 75% but low specificity of 58% (32).…”

Section: Discussionmentioning

confidence: 99%

A Meta-Analytic Review of the Value of miRNA for Multiple Sclerosis Diagnosis

et al. 2020

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Backgrounds and Purpose: Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system. The etiology of MS is unclear, disease diagnosis mainly based on symptoms, and lacks effective laboratory test index. Circulating microRNAs (miRNAs) as sensitive biomarkers have been widely studied, the expression levels of certain miRNAs are dynamically changed in MS patients. This meta-analysis aims to assess the overall diagnostic accuracy of circulating miRNAs for MS. Methods: We searched PubMed, EMBASE, Cochrane Library, CNKI databases as of July 20, 2019. QUADAS was used to assess the quality of included studies. All studies were processed by Stata 15.0 software. Eleven articles with 600 patients with MS and 389 controls were included. Results: The sensitivity and specificity, PLR, NLR, and DOR of the overall studies were 0.81 (95% CI 0.77-0.84), 0.75 (95% CI 0.68-0.81), 3.3 (95% CI 2.5-4.3), 0.25 (95% CI 0.20-0.32), 13 (95% CI: 8-20), and 0.85 (95% CI 0.82-0.88). Subgroup analysis indicated that miRNA assay had higher diagnostic accuracy for relapsing-remitting MS (RRMS) when compared with other MS subtypes. Conclusion: Our study performed a meta-analysis to generate an estimate of the relevance of miRNA change and the occurrence of MS, and revealed circulating miRNAs has the potential to be used for MS diagnosis, especially for RRMS. Future studies should clarify to which specific miRNAs can accurately diagnose disease subtypes. The miRNA-related pathogenesis may provide theoretical basis for drug development for early intervention.

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Dysregulated Network of miRNAs Involved in the Pathogenesis of Multiple Sclerosis

Cited by 52 publications

References 97 publications

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial

CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

A Meta-Analytic Review of the Value of miRNA for Multiple Sclerosis Diagnosis

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