Altered expression of microRNAs may predict therapeutic response in rheumatoid arthritis patients

BackgroundEpigenetic alternations of microRNAs (miRNAs) can contribute to the pathogenesis and progression of rheumatoid arthritis (RA). This study aimed to measure the expression level of peripheral blood miRNAs, as well as their target mRNAs, in RA patients and healthy controls (HCs), and to evaluate the potential of miRNAs as promising non-invasive biomarkers of treatment response.MethodsThe peripheral expression of miRNAs, including miR-146a, miR-146b, miR-150, miR-155, miR-125a-5p, miR-223, miR-26a, and miR-21, as well as their target mRNAs, was analyzed in 90 RA patients and 30 HCs via quantitative real-time polymerase chain reaction (RT-PCR) assay. We compared differences between the patients in terms of good response (GR; n = 55) and poor response (PR; n = 35) to the conventional therapeutic approach.ResultsAll miRNAs were significantly overexpressed in RA patients. The expression of miR-155, miR-150, miR-146a, miR-146b, miR-125a-5p, and miR-223 increased in both groups of RA patients, compared to HCs, and miR-26a and miR-21 were the only upregulated miRNAs in the GR group versus HCs. Among the upregulated miRNAs, miR-125a-5p expression significantly changed in GR and PR patients (P = 0.047). The ROC curve analysis indicated the potential involvement of miR-125a-5p in the pathogenesis of RA. We also observed the downregulated expression of GATA3, RORC, FOXP3, TBX21, STAT1, and TRAF6 in RA patients versus HCs.ConclusionOur findings indicated that different expression levels of miR-125a-5p in the GR and PR groups of patients may serve as a therapeutic response biomarker, which can be also used as a target for therapeutic interventions.     

Contribution of microRNA 24–3p and Erk1/2 to interleukin‐6‐mediated plasma cell survival

Plasma cells can survive for long periods and continuously secrete protective antibodies, but plasma cell production of autoantibodies or transformation to tumor cells is detrimental. Plasma cell survival depends on exogenous factors from the surrounding microenvironment, and largely unknown intracellular mediators that regulate cell homeostasis. Here we investigated the contribution of the microRNA 24–3p (miR‐24–3p) to the survival of human plasma cells under the influence of IL‐6 and SDF‐1α (stromal cell derived factor 1), both of which are bone marrow survival niche mediators. Deep sequencing revealed a strong expression of miR‐24–3p in primary B cells, plasma blasts, plasma cells, and in plasmacytoma cells. In vitro studies using primary cells and the plasmacytoma cell line RPMI‐8226 revealed that (i) expression of miR‐24–3p mediates plasma cell survival, (ii) miR‐24–3p is upregulated by IL‐6 and SDF‐1α, (iii) IL‐6 mediates cell survival under ER stress conditions via miR‐24–3p expression, and (iv) IL‐6‐induced miR‐24–3p expression depends on the activity of the MAP kinase Erk1/2. These results suggest a direct connection between an external survival signal and an intracellular microRNA in regulating plasma cell survival. miR‐24–3p could therefore be a promising target for new therapeutic strategies for autoimmune and allergic diseases and for multiple myeloma.     

Elucidation of the Receptors in Macrophage and Plasmodium Yoelii Interactions.

Binding of hyperimmune serum opsonized merozoites of Plasmodium Yoelii nigerensis to trypsinized macrophages suggested it to be mediated by FcII receptor. Receptor blocking inhibition with monoclonal antibody 2.4G2 directed against Fc receptor for IgG1/IgG2b provided evidence that Fcγ2b on macrophage played an important role in the merozoite-macrophage interactions. In addition, a neuraminidase sensitive receptor was noted to mediate the binding of P. yeelii merozoites in the absence of serum. Binding inhibition studies with two monosaccharides, D-mannose and α-methyl mannoside, indicated the role of Mannose/Fucose receptor on macrophage in this interaction.     

MicroRNA在微血管病变调控机制方面的研究进展

Microangiopathy is characterized by capillary basement membrane thickening and microthrombus formation. The process of microangiopathy involves multiple organs and tissues, and seriously endangers the patients’ health and quality of life during the later stage. Recent evidence shows that microRNAs play an important role in the regulatory mechanism of microangiopathy, including inflammatory response, oxidative stress, abnormalities of glucose and lipid metabolism, abnormal activation of the rennin-angiotensin system and so on. The regulatory mechanism has unique features of microangiopathy in different organs. At present, more and more attention has been paid to the roles of microRNAs in the pathogenesis of microangiopathy.     

胎儿生长受限的表观遗传学研究进展

胎儿生长受限是产科重要的特发性疾病之一。近年来研究发现表观遗传变异在胎儿生长受限等妊娠特发性疾病的发生发展中起着重要作用,检测环境暴露和引起胎儿生长相关的表观遗传学改变可为胎儿生长受限的生物学发展和成年后疾病风险度的评估研究提供重要线索。本文就表观遗传学在胎儿生长受限领域的研究现状和进展做一综述,为胎儿生长受限的预防、诊断和治疗提供一种新思路。     

MiR-340经组织型纤溶酶原激活剂调控施万细胞的纤溶能力

目的:探讨microRNA-340(miR-340)对施万细胞纤溶能力的调控作用及作用的靶基因。方法:采用溶圈实验来检测miR-340对施万细胞纤溶能力的影响,用荧光素酶双报告基因系统确定miR-340与组织型纤溶酶原激活剂的靶向关系,用实时定量聚合酶链反应检测坐骨神经夹伤后组织型纤溶酶原激活剂mRNA和miR-340的表达变化。结果:miR-340能够抑制施万细胞的纤溶能力,并直接靶向作用于组织型纤溶酶原激活剂的3’UTR,坐骨神经夹伤后组织型纤溶酶原激活剂mRNA与miR-340的表达呈负相关性。结论:miR-340通过直接靶向组织型纤溶酶原激活剂的3’UTR,从而下调靶基因组织型纤溶酶原激活剂的表达抑制施万细胞的纤溶能力。     

Blood-based biomarkers for early detection of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present,early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a noninvasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC.This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.