Micro RNA 499 gene expression and interleukin 17 in Egyptian patients with Behçet’s disease

BackgroundHigh levels of interleukin 17 are expressed in active Behcet’s disease (BD) patients. High miRNA-499 relative expression is known to be associated with vascular manifestations and aneurysms in BD.Aim of the workTo detect miRNA-499 relative expression and interleukin 17 serum levels in BD patients and find their association to clinical characteristics and disease activity.Patients and methodsBlood samples were obtained from 40 Egyptian BD patients and 40 matched controls. The BD current activity form (BDCAF) was estimated. Relative expression of miRNA-499 was measured by real-time polymerase chain reaction. Serum IL-17 was also measured in by enzyme-linked immunosorbent assay.ResultsThe mean age of the patients was 34.4 ± 10.9 years, disease duration was 8.9 ± 0.8 years and age at onset was 25.5 ± 7.2 years and they were 33 males and 7 females. All patients had oral ulcers, 85% had genital ulcers and 75% had ocular manifestations. The mean BDCAF was 1.54 ± 1.78. Levels of miRNA-499 relative expression were significantly higher in BD cases versus controls (4.2 ± 2.1 vs. 1.1 ± 0.3ΔΔC_t respectively; p < 0.001). Levels of IL 17 were significantly higher in BD cases versus controls (86.9 ± 31.2 vs. 34.7 ± 4.4 pg/ml respectively; p < 0.001). There was a non-significant correlation between miRNA and IL 17 in patients (r = −0.06, p < 0.71). IL17 was significantly associated only with the occurrence of arthritis (p = 0.03). There was no significant association between miRNA-499 or IL-17 with the BDCAF (r = 0.22, p = 0.12 and r = −0.002, p = 0.99; respectively).ConclusionMicro RNA-499 relative expression and IL17 levels were significantly higher in BD patients compared to the controls.     

miR-7在肾癌中的表达及临床意义研究

目的检测肾细胞癌组织及相应癌旁正常组织中miR-7的表达,分析18达与临床病理特征之间的关系,为进一步研究miR-7在肾癌的发生发展中作用奠定基础。方法收集48例经手术切除的配对肾癌及癌旁组织标本,提取组织中总RNA,经逆转录获得cDNA,采用实时荧光定量PCR（RT-qPCR）方法检测标本中miR-7表达量,并通过统计学软件分析其表达量与患者临床病理特征之间的相关性。结果与相应癌旁组织相比,肾癌组织中miR-7表达量明显升高,其中34例（70.8%）肾癌标本miR-7表达上调,14例（29.2%）表达下调,差异有统计学意义（P〈0.05）。肾细胞癌中miR-7表达上调与患者年龄、性别、肾癌组织类型、TNM分期、AJCC临床分期无相关性（P〉0.05）。结论 miR-7在肾癌组织中明显高表达,提示其可能与肾癌的发生和发展相关,可能成为肾癌早期诊断、治疗乃至预后判断的新的生物标记物。     

miRNA-449a在肺癌组织中的表达及其检测意义

目的探讨miRNA-449a在肺癌组织中的表达及其临床应用价值。方法收集右江族医学院附属医院2011年1月1日~2013年6月30日收治的58例肺癌患者为研究对象,采用反转录荧光定量聚合酶链式反应(RT-PCR)检测miRNA-449a在肺癌组织和癌旁正常组织中的表达量,分析miRNA-449a与临床病理特征的关系,并采用荧光电子显微镜观察miRNA-449a模拟物对体外培养肺癌细胞株95D细胞凋亡的影响。结果鳞癌组和腺癌组miRNA-449a平均表达量均明显低于癌旁正常对照组(LSD-t=6.712,P=0.000;LSD-t=4.572,P=0.000),其相对表达量与瘤体大小(u=78.412,P=0.012)有关,与患者年龄(u=920.000,P=0.615)、性别(u=800.000,P=0.215)、病理类型(χ2=4.221,P=0.155)和临床分期(u=754.000,P=0.009)无关。与阴性对照组比较,miRNA-449a模拟物可明显促进肺癌细胞的凋亡,且呈剂量依赖性。结论 miRNA-449a在肺癌组织中呈低表达,可诱导肺癌细胞凋亡,发挥抑癌基因的作用,可能成为肺癌早期诊断与治疗的新分子靶标。     

孕妇血清微小RNA-423对胎儿神经管缺陷产前诊断的意义

目的 母亲血清中微小RNA(microRNA,miRNA)的发现为无创性产前诊断开辟了新途径.但是对神经管缺陷胎儿母亲血清中妊娠相关的miRNA的研究甚少.该文旨在研究微小RNA-423(mi-croRNA-423,miR-423)在神经管缺陷胎儿孕妇血清中的异常表达及其作为潜在诊断标志物的临床价值.方法 33例产前超声检查确诊为胎儿神经管缺陷的患儿为研究对象,其中脊柱裂22例,无脑儿11例;33例胎儿健康孕妇为对照组.所有孕妇均于清晨空腹抽外周静脉血5ml离心后取血清,提取血清总RNA,用Real-time RT-PCR方法测定miR-423表达水平.并用ROC曲线分析用miR-423诊断胎儿神经管缺陷的价值.结果 神经管缺陷胎儿孕妇血清中miR-423含量(0.96±0.14)明显低于健康胎儿孕妇对照组(2.28±0.43),P＜0.05.ROC分析miR-423曲线下面积为0.711(95％ CI:0.566～0.856)(P＜0.05).另外,对不同类型的神经管缺陷孕妇血清中的miR-423表达水平分析发现,只有在无脑儿中表达降低(0.58±0.08)差异有统计学意义.结论 孕妇血清中miR-423可作为胎儿神经管缺陷的无创性产前诊断标志物,具有潜在的临床价值,可能预示胎儿神经管缺陷严重程度.     

MiR-122 and other microRNAs as potential circulating biomarkers of drug-induced liver injury

Introduction: Drug-induced liver injury (DILI) is a severe adverse drug reaction which is of major concern to patients, clinicians and the pharmaceutical industry. Accurate and rapid detection of DILI is important for patient stratification and treatment in the clinic and benefits preclinical drug design and risk assessment. MicroRNAs (miRNAs) offer a potential new and improved class of circulating biomarkers of DILI over the current gold standard biomarkers.

Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI. Furthermore, the use of miRNAs as potential markers of progression of DILI and specific zonated damage within the liver is discussed.

Expert commentary: MiRNAs offer more sensitive and specific markers over the current biomarkers for DILI. Combinations of different miRNAs may be able to relay the location of DILI and the progression of disease. More studies using different hepatotoxins apart from acetaminophen will ultimately strengthen the case for the clinical introduction of miRNAs as biomarkers of DILI.     

Relation of genetic polymorphisms in microRNAs with diastolic and systolic function in type 2 diabetes mellitus

Background and aimsType 2 diabetes mellitus (T2DM) has high risk of developing cardiac dysfunction, increasing of either cardiovascular death or hospitalization for heart failure. MicroRNAs (miRNA) affect cardiac function of T2DM. The aim of this study was to investigate the relationships between five miRNA single nucleotide polymorphisms (SNP) and diastolic and systolic function of T2DM.Methods and resultsThree hundred untreated T2DM subjects were included. Each subject underwent SNP genotyping, conventional echocardiography, tissue doppler imaging, and speckle tracking imaging. The effects of miRNA SNPs on diastolic and systolic function were evaluated. The diastolic function of T2DM subjects with miR-133a-1-rs8089787 wild genotype or let-7f-rs10877887 variant genotype was lower than those with miR-133a-1-rs8089787 variant genotype or let-7f-rs10877887 wild genotype, manifesting as higher left atrial volume index, lower mean E′, and higher E/E’ (P < 0.05). There were no significant effects of miR-133a-2-rs13040413, let-7a-1-rs13293512 and miR-27a-rs895819 on the diastolic function of T2DM subjects (P > 0.05). These five miRNA SNPs had no effect on the systolic function of T2DM subjects (P > 0.05).ConclusionsMiRNA-133a-1-rs8089787 and let-7f-rs10877887 were associated with impaired cardiac diastolic function in T2DM. The findings may be a promising therapeutic targets for preventing diastolic dysfunction in T2DM.     

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.