Evaluation of serum miR-191-5p, miR-24-3p, miR-128-3p, and miR-376c-3 in multiple sclerosis patients (original) (raw)
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2021
Background: MicroRNAs (miRNAs) affect the differentiation and function of inflammatory cells. In addition, miRNAs can regulate the expression of pro-inflammatory genes in neuron cells. Therefore, the relationship between the expression of miRNAs and inflammatory markers in the cerebrospinal fluid of individuals with multiple sclerosis was investigated.Methods: RT-PCR determined the expression levels of MiR-21, MiR-155, Mir-182, and Mir-437 in CSF samples from patients with multiple sclerosis (MS) and the control group. The levels of the inflammatory cytokines IL -1β, IL -6, and TNF-α in CSF were measured by ELISA. The level of high-sensitivity C-reactive protein (hs-CRP) was measured by the quantitative turbidometric technique.Results: The expression of miRNAs and inflammatory factors were higher in the CSF of patients with MS than in the control group, and this difference was significant (P <0.05). The results of Receiver Operating Characteristics (ROC) analysis show that the ar...
Biomarkers of multiple sclerosis: current findings
Degenerative Neurological and Neuromuscular Disease
Multiple sclerosis (MS) is an autoimmune disease affecting the brain and spinal cord that is associated with chronic inflammation leading to demyelination and neurodegeneration. With the recent increase in the number of available therapies for MS, optimal treatment will be based on a personalized approach determined by an individual patient's prognosis and treatment risks. An integral part of such therapeutic decisions will be the use of molecular biomarkers to predict disability progression, monitor ongoing disease activity, and assess treatment response. This review describes current published findings within the past 3 years in biomarker research in MS, specifically highlighting recent advances in the validation of cerebrospinal fluid biomarkers such as neurofilaments (light and heavy chains), chitinases and chitinase 3-like proteins, soluble surface markers of innate immunity, and oligoclonal immunoglobulin M antibodies. Current research in circulating miRNAs as biomarkers of MS is also discussed. Continued validation and testing will be required before MS biomarkers are routinely applied in a clinical setting.
Journal of Neuroinflammation, 2019
Background MicroRNAs (miRNAs) have been reported as deregulated in active brain lesions derived from patients with multiple sclerosis (MS). In there, these post-transcriptional regulators may elicit very important effects but proper identification of miRNA candidates as potential biomarkers and/or therapeutic targets is scarcely available. Objective The aim of the study was to detect the presence of a set of candidate miRNAs in cell-free cerebrospinal fluid (CSF) and to determine their association with gadolinium-enhancing (Gd+) lesions in order to assess their value as biomarkers of MS activity. Methods Assessment of 28 miRNA candidates in cell-free CSF collected from 46 patients with MS (26 Gd+ and 20 Gd− patients) was performed by TaqMan assays and qPCR. Variations in their relative abundance were analyzed by the Mann-Whitney U test and further evaluated by receiver operating characteristic (ROC) analysis. Signaling pathways and biological functions of miRNAs were analyzed using ...
Journal of Molecular Neuroscience, 2014
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90 % of patients are diagnosed with the relapsing-remitting form (RRMS). The name "multiple sclerosis" pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression. At present, small noncoding RNA particles-microRNA (miRNA, miR) seem to be particularly noteworthy, as they take part in posttranscriptional regulation of expression of various genes. Changes in composition as well as function This article was based on author's doctoral thesis entitled "Evaluation of microRNA expression as potential biomarkers of activation of the immune system in the course of multiple sclerosis (MS)" and contains excerpts thereof.
SVU-International Journal of Medical Sciences
Background: There is a growing need for biomarkers that can help in early diagnosis of multiple sclerosis (MS) and in recognizing patients with MS activity. Moreover, many studies are recently focusing on biomarkers that may help in diagnosis of the transition from relapsing remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS). Circulating microRNAs (miRNAs) are now considered promising biomarkers. Objectives: Studying the role of plasma miRNA-145 and miRNA-484 in the diagnosis of MS, disease activity and in diagnosing the transition from RRMS to SPMS. Patients and Methods: Forty-six subjects of both sexes were included, 31 patients with MS)21 with RRMS, 8 with SPMS and Two patients with primary progressive multiple sclerosis (PPMS)) and 15 healthy controls. Expression analysis of plasma miRNAs; miR-145 and miR-484 were assessed by real-time quantitative polymerase chain reaction (PCR) after miRNA extraction. Results: MicroRNAs 145 and 484 could significantly discriminate between MS cases and controls, with best cutoff values > 0.6 and > 1.7 respectively. They could also significantly discriminate between active and inactive MS cases, with best cutoff values > 0.8 and > 2 respectively. Plasma miRNA-145 could discriminate between RRMS and SPMS cases, with best cutoff value ≤1.4. Conclusion: Plasma miRNAs 145 and 484 might be used as promising biomarkers for early diagnosis of MS and in diagnosis of disease activity. Plasma miRNA-145 could be also helpful in diagnosis of the transition from RRMS to SPMS.
Decreased circulating miRNA levels in patients with primary progressive multiple sclerosis
Multiple Sclerosis Journal, 2013
Emerging evidence underlines the importance of micro(mi)RNAs in the pathogenesis of multiple sclerosis (MS). Freecirculating miRNAs were investigated in serum from MS patients compared to controls. Statistically significant decreased levels of miR-15b, miR-23a and miR-223 were observed in MS patients (p < 0.05). Results were validated and replicated in two further independent MS populations. A direct correlation between miRNA levels and the EDSS score was determined in PPMS (p < 0.007). The generalized trend toward miRNA down-regulation could result in over-expression of target genes involved in disease pathogenesis. Circulating miRNA profiling could thus represent a new avenue to identify easily detectable disease biomarkers.
Altered Expression of Circulating miR-377 and miR-98 in Relapsing-remitting Multiple Sclerosis
International Journal of Medical Laboratory, 2020
Background and Aims: Multiple sclerosis (MS) has been assumed to be a Complex and indecipherable disease, and poorly understood with regard to etiology which is characterized by relapses and remissions. The expression of microRNAs (miRNAs) is known to be associated with the regulation of immune responses. Recently, investigations have reported that miRNA expression profiles in blood cells become changed in MS. The aim of this study was to elucidate the alterations in the expression of circulating miR377 and miR-98 in 60 relapsing-remitting MS (RRMS) patients in comparison with controls. Materials and Methods: This study was conducted using a quantitative real-time polymerase chain reaction method to explore the expression of circulating miR-377 and miR-98 in peripheral blood mononuclear cells from 60 RRMS patients, 30 of whom were recurring patients, 30 were two months after relapse patients, and 30 others were controls, in order to examine the association of expression level of the...
International Journal of Molecular Sciences
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Its first clinical presentation (clinically isolated syndrome, CIS) is often followed by the development of relapsing–remitting MS (RRMS). The periphery-to-CNS transmission of inflammatory molecules is a major pathophysiological pathway in MS. This could include signalling via extracellular vesicle (EV) microRNAs (miRNAs). In this study, we investigated the serum EV miRNome in CIS and RRMS patients and matched controls, with the aims to identify MS stage-specific differentially expressed miRNAs and investigate their biomarker potential and pathophysiological relevance. miRNA sequencing was conducted on serum EVs from CIS-remission, RRMS-relapse, and viral inflammatory CNS disorder patients, as well as from healthy and hospitalized controls. Differential expression analysis was conducted, followed by predictive power and target-pathway analysis. A moderate number of dysregulated ...
Scientific Reports, 2020
It is widely recognized that monocytes-macrophages adopt a wide variety of phenotypes, influencing the inflammatory activity and demyelination in Multiple Sclerosis (MS). However, how the phenotype of human monocytes evolves in the course of MS is largely unknown. The aim of our preliminary study was to analyse in monocytes of relapsing-remitting and progressive forms of MS patients the expression of a set of miRNAs which impact monocyte-macrophage immune function and their communication with brain cells. Quantitative PCR showed that miRNAs with anti-inflammatory functions, which promote pro-regenerative polarization, are increased in MS patients, while pro-inflammatory miR-155 is downregulated in the same patients. These changes may indicate the attempt of monocytes to counteract neuroinflammation. miR-124, an anti-inflammatory marker but also of myeloid cell quiescence was strongly downregulated, especially in progressive MS patients, suggesting complete loss of homeostatic monocyte function in the progressive disease phase. Profiling of miRNAs that control monocyte polarization may help to define not only the activation state of monocytes in the course of the disease but also novel pathogenic mechanisms.
miRNA Signature in CSF From Patients With Primary Progressive Multiple Sclerosis
Neurology - Neuroimmunology Neuroinflammation
Background and ObjectivesPrimary progressive multiple sclerosis (PPMS) displays a highly variable disease progression with a characteristic accumulation of disability, what makes difficult its diagnosis and efficient treatment. The identification of microRNAs (miRNAs)-based signature for the early detection in biological fluids could reveal promising biomarkers to provide new insights into defining MS clinical subtypes and potential therapeutic strategies. The objective of this cross-sectional study was to describe PPMS miRNA profiles in CSF and serum samples compared with other neurologic disease individuals (OND) and relapsing-remitting MS (RRMS).MethodsFirst, a screening stage analyzing multiple miRNAs in few samples using OpenArray plates was performed. Second, individual quantitative polymerase chain reactions (qPCRs) were used to validate specific miRNAs in a greater number of samples.ResultsA specific profile of dysregulated circulating miRNAs (let-7b-5p and miR-143-3p) was f...