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复发缓解型多发性硬化症患者外周血单个核细胞中潜在生物标志物的鉴定

Identification of Potential Biomarkers in the Peripheral Blood Mononuclear Cells of Relapsing-Remitting Multiple Sclerosis Patients.

作者信息

Golabi Marjan, Fathi Farshid, Samadi Morteza, Hesamian Mohammad Sadegh, Eskandari Nahid

机构信息

Department of Medical Immunology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Inflammation. 2022 Aug;45(4):1815-1828. doi: 10.1007/s10753-022-01662-9. Epub 2022 Mar 28.

Abstract

Multiple sclerosis (MS) is described as an immune disorder with inflammation and neurodegeneration. Relapsing-remitting MS (RRMS) is one of the most common types of MS. The diagnostic manner for this disorder typically includes the usage of magnetic resonance imaging (MRI); however, this is not always a very precise diagnostic method. Identification of molecular biomarkers in RRMS body fluids samples compared to healthy subjects can be useful to indicate the normal and pathogenic biological processes or pharmacological responses to drug interaction. In this regard, this study evaluated different miRNAs in isolated peripheral blood mononuclear cells (PBMCs) of RRMS compared to controls and their correlations with altered T regulatory type 1 (Tr1) cells, osteopontin (OPN), and interleukin 10 (IL-10) levels. The frequency of Tr1 cells was measured using flow cytometry. Also, the expressions of different miRNAs were evaluated via quantitative real-time polymerase chain reaction (RT-qPCR) and plasma levels of IL-10 and OPN were tested by enzyme-linked immunosorbent assay (ELISA). The obtained results showed the Tr1 cells' frequency, Let7c-5p, and miR-299-5p levels decreased in RRMS patients to about 59%, 0.69%, and 20% of HCs, respectively, (P < 0.05). The miR-106a-5p levels increased about 7.5-fold in RRMS patients in comparison to HCs (P < 0.05). Moreover, the results showed that there was an increased negative association between Tr1 frequency and plasma-OPN levels in RRMS patients in comparison to HCs and also, we found a moderate positive correlation between plasma-IL-10 and miR-299-5p expression of RRMS patients. Overall, it may be possible to use these biomarkers to improve the diagnostic process. These biomarkers may also be considered for clinical and therapeutic studies in the future.

摘要

多发性硬化症(MS)被描述为一种伴有炎症和神经退行性变的免疫紊乱疾病。复发缓解型多发性硬化症(RRMS)是MS最常见的类型之一。该疾病的诊断方式通常包括使用磁共振成像(MRI);然而,这并不总是一种非常精确的诊断方法。与健康受试者相比,在RRMS体液样本中鉴定分子生物标志物有助于指示正常和致病的生物学过程或对药物相互作用的药理反应。在这方面,本研究评估了RRMS患者与对照组相比,分离的外周血单个核细胞(PBMC)中不同的微小RNA(miRNA),以及它们与1型调节性T细胞(Tr1)、骨桥蛋白(OPN)和白细胞介素10(IL-10)水平变化的相关性。使用流式细胞术测量Tr1细胞的频率。此外,通过定量实时聚合酶链反应(RT-qPCR)评估不同miRNA的表达,并通过酶联免疫吸附测定(ELISA)检测IL-10和OPN的血浆水平。获得的结果显示,RRMS患者中Tr1细胞的频率、Let7c-5p和miR-299-5p水平分别降至健康对照者的约59%、0.69%和20%(P<0.05)。与健康对照者相比,RRMS患者中miR-106a-5p水平增加了约7.5倍(P<0.05)。此外,结果表明,与健康对照者相比,RRMS患者中Tr1频率与血浆OPN水平之间的负相关性增加,并且我们发现RRMS患者血浆IL-10与miR-299-5p表达之间存在中度正相关。总体而言,使用这些生物标志物可能有助于改善诊断过程。这些生物标志物未来也可考虑用于临床和治疗研究。

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