Novel determinants preventing achievement of major cardiovascular targets in type 2 diabetes

BackgroundT2DM management requires tight control of 3 critical quality indicators to prevent vascular complications: LDL-C, SBP, and HbA_1c. This study evaluated the rate of T2DM patients attaining these critical quality indicators, and the pathophysiological or cardiometabolic traits predicting goal achievement.Patients and methodsCross-sectional analysis evaluating combined goal achievement (LDL-C < 100 mg/dL; SBP < 130 mmHg and HbA_1c < 7.0%) in 1005 T2DM outpatients (654 men) followed in a university hospital multidisciplinary department. Triple-goal achievers were compared to non-achievers regarding sociodemographics; anthropometrics; homeostatic model assessment (HOMA; β-cell function (B); insulin sensitivity (S); hyperbolic product (B × S)); CV and glucose-lowering drugs; micro-/macro-vascular outcomes; and 10-year UKPDS risk.ResultsEighty-eight patients (9%; ((3 targets) group) reached all goals, whereas 917 patients (91%; ((0–2 target(s)) group) missed 1, 2 or all 3 goals. Compared to (0–2 target(s)), (3 targets) had shorter diabetes duration; less familial diabetes history; lower waist/visceral fat; higher β-cell function and hyperbolic product (B × S); lower (B × S) loss rate and less metabolic syndrome (all p < 0.05). They had lower apoB and triglycerides; and a 28% prevalence of atherogenic dyslipidemia (vs. 40% in (0–2 target(s)); p 0.0398). Microangiopathy (36% vs. 53%) and 10-year CAD risk (13% vs. 18%) were also significantly lower in (3 targets).ConclusionsThe subset of T2DM patients achieving all critical quality indicators are characterized by a less severe cardiometabolic phenotype, while exhibiting a less pronounced alteration of their residual β-cell function. These differences are related to fewer microvascular outcomes and lower 10-year CV risk.     

Incorporating structure to predict microRNA targets

MicroRNAs (miRNAs) are a recently discovered set of regulatory genes that constitute up to an estimated 1% of the total number of genes in animal genomes, including Caenorhabditis elegans, Drosophila, mouse, and humans [Lagos-Quintana, M., Rauhut, R., Lendeckel, W. & Tuschl, T. (2001) Science 294, 853-858; Lai, E. C., Tomancak, P., Williams, R. W. & Rubin, G.M. (2003) Genome Biol. 4, R42; Lau, N. C., Lim, L. P., Weinstein, E. G. & Bartel, D. P. (2001) Science 294, 858-862; Lee, R. C. & Ambros, V. (2001) Science 294, 862-8644; and Lee, R. C., Feinbaum, R. L. & Ambros, V. (1993) Cell 115, 787-798]. In animals, miRNAs regulate genes by attenuating protein translation through imperfect base pair binding to 3' UTR sequences of target genes. A major challenge in understanding the regulatory role of miRNAs is to accurately predict regulated targets. We have developed an algorithm for predicting targets that does not rely on evolutionary conservation. As one of the features of this algorithm, we incorporate the folded structure of mRNA. By using Drosophila miRNAs as a test case, we have validated our predictions in 10 of 15 genes tested. One of these validated genes is mad as a target for bantam. Furthermore, our computational and experimental data suggest that miRNAs have fewer targets than previously reported.     

A biochemical approach to identifying microRNA targets

Identifying the downstream targets of microRNAs (miRNAs) is essential to understanding cellular regulatory networks. We devised a direct biochemical method for miRNA target discovery that combined RNA-induced silencing complex (RISC) purification with microarray analysis of bound mRNAs. Because targets of miR-124a have been analyzed, we chose it as our model. We honed our approach both by examining the determinants of stable binding between RISC and synthetic target RNAs in vitro and by determining the dependency of both repression and RISC coimmunoprecipitation on miR-124a seed sites in two of its well characterized targets in vivo. Examining the complete spectrum of miR-124 targets in 293 cells yielded both a set that were down-regulated at the mRNA level, as previously observed, and a set whose mRNA levels were unaffected by miR-124a. Reporter assays validated both classes, extending the spectrum of mRNA targets that can be experimentally linked to the miRNA pathway.     

Studied microRNA gene expression in human hepatocellular carcinoma by microRNA microarray techniques

AIM: To achieve a better understanding of the molecular mechanisms of micro RNA expression changes involved in hepatocellular carcinoma.METHODS: In this research process, patients were not treated with antivirals, immunosuppressants or immunomodulators for at least 6 mo before collecting serum. The study population was composed of 35 outpatient hepatitis B virus(HBV) cases and 12 healthy control cases from the Affiliated Hospital of Inner Mongolia Medical University(Inner Mongolia, China) from July 2013 to April 2014. The 35 HBV cases were divided into two groups: a hepatocirrhosis group with 20 cases and a liver cancer group with 15 cases. All 35 cases carried HBs Ag. The diagnostic criteria followed the European Association for the Study of the Liver 2012(EASL2012) standards. Micro RNA(mi RNA) was extracted from a control group of patients, a group with hepatocirrhosis and a group with liver cancer and its quality was analyzed using the human V2 micro RNA expression beadchip. Cluster analysis and a radar chart were then applied to the mi RNA changes.RESULTS: The mi RNA-qualified rate of human serum samples was 93%. The concentration of a single sample was 200 ng/μL and the volume was 5 μL.All mi RNA serum samples were uncontaminated by the genome. The Mann-Whitney test showed significant differences in mi RNA between each group, with a detection P-value of 0.05. Illumina software was set up with Diff Score set to ± 13, meaning that P = 0.001.There were significant changes in mi RNA expression between the three groups. mi RNA-183 was the most up-regulated, followed by mi RNA-373. mi RNA-129 and mi RNA-188 were both strongly down-regulated and mi RNA-378 was down-regulated a small amount. The liver cancer group had greater changes, which indicated that changes in mi RNA expression levels were caused by hepatocirrhosis. The liver cancer disease course then further increased these changes. In the pentagon created by these five mi RNAs, three groups showed significant deviation. The liver cancer group had a bigger deviation trend. The chart indicated that mi RNA expression changes occurred in the hepatocirrhosis group, which increased in the liver cancer disease course and were irreversible.CONCLUSION: There was a significant relationship between the irreversible up-regulation of mi RNA-183/373 and down-regulation of mi RNA-129/188/378 and incidences of hepatocirrhosis and liver cancer.     

外泌体来源微小RNA在心血管疾病中作用研究进展

在不同的病理生理状态下,细胞可分泌包含有特定内含物的外泌体至细胞外环境中。其中,来源于外泌体的微小RNA(miRNA)能够参与细胞间的物质传递和信号转导。近年来,人们逐渐认识到外泌体及其相关的miRNA在心血管疾病发病过程中的重要作用。本文介绍了外泌体的基本特征及外泌体来源的miRNA的生物学特性,讨论了外泌体来源的miRNA在不同心血管疾病中的表达情况。     

胃癌相关microRNA及其作用靶点的研究进展

microRNA(miRNA)是近年来发现的一类非编码单链小分子RNA,它的发现揭示了一种新的基因表达调控方式。其功能具有多样性,通过参与对靶基因的调控而影响细胞的生理及病理过程。近年发现许多miRNA与多种肿瘤的发生、发展及预后关系密切。胃癌是消化系统常见的恶性肿瘤之一,目前已发现一些miRNA及其相应的作用靶点与胃癌细胞的增殖、侵袭、转移、凋亡、对放射化学疗法的敏感性及DNA甲基化有密切关系,为对胃癌的研究提供新的途径。此文就近年胃癌相关miRNA及其作用靶点的研究作一综述。     

微小RNA与炎症相关心血管疾病的研究进展

<正>微小RNA(microRNA,miRNA)是一类进化上高度保守,长度约18~22个核苷酸的不编码蛋白质的单链小分子RNA,能够通过与靶mRNA特异性的碱基配对引起靶mRNA的降解或者抑制其翻译,从而对基因进行转录后表达的调控[1]。炎症是具有血管系统的活体组织对损伤因子所发生的防御反应。近年,心血管疾病发病率和死亡率呈上升趋势,严重威胁人类的生命健康。已知多种心血管疾病都与炎     

Novel targets in aggressive lymphoma

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消化道肿瘤microRNA研究进展

肿瘤的发生是一个多阶段、多基因突变积累的过程。microRNA的发现使人们对肿瘤的形成有了新的认识,众多研究表明microRNA与肿瘤发生、发展密切相关。microRNA在消化道肿瘤发病机制研究中也占有重要地位,并有望成为消化道肿瘤的早期诊断、鉴别诊断、临床分期、个性化治疗指导、预后评估的分子标志物与药物靶点。此文就近几年消化道肿瘤microRNA研究进展作一综述。     

Novel targets in gastric and esophageal cancer

Esophageal cancer (EC) and gastric cancer (GC) constitute a major cause of cancer deaths worldwide. Recent improvements in both surgical techniques and adjuvant/neoadjuvant chemotherapy, radiotherapy or both have increased the survival of patients with loco-regional disease. However, most patients with GC or EC have advanced disease either at diagnosis or during the follow-up, and despite recent advances, these patients still do poorly. Understanding of the molecular pathways that characterize cell growth, cell cycle, apoptosis, angiogenesis and invasion has provided novel targets in cancer therapy. In this review we describe the current status of targeted therapies in the treatment of EC and GC, including EGFR inhibitors, antiangiogenic agents, cell cycle inhibitors, apoptosis promoters and matrix metalloproteinases inhibitors. The emerging data from the clinical development of these compounds has provided novel opportunities in the treatment of EC and GC that will probably translate into clinical benefit for patients with these common malignancies.     

microRNA Let-7在心血管疾病中的研究进展

microRNA let-7家族是在秀丽隐杆线虫中发现的长度21nt的microRNA之一。最近的研究发现它在心血管系统起到重要的调控作用。Let-7成员在心血管组织中特异性表达使其在心脏发育及心脏疾病的发生发展中发挥重要作用。目前, let-7的靶向基因主要是TLR4、LOX-1、Bcl-xl和AGO1,确定let-7靶基因和信号通路在心脏疾病的临床诊断和治疗上具有重要的应用前景。Let-7可能为一个潜在的治疗心血管疾病的目标。本文对 let-7在心血管疾病中的研究进展进行综述。     

微小RNA与脏器纤维化的研究进展

微小RNA（miRNA）是一类长18～24个核苷酸的内源性非编码小RNA,在转录后水平调控靶基因的表达。miRNA参与细胞增殖、分化、凋亡及肿瘤形成等生物学过程。近年来发现,miRNA也参与心肌、肾脏和肝脏的纤维化过程,该文对miRNAs生物学特征及其在脏器纤维化过程中的作用的相关研究进展作一综述。     

The art of microRNA research

Originally identified as moderate biological modifiers, microRNAs have recently emerged as powerful regulators of diverse cellular processes with especially important roles in disease and tissue remodeling. The rapid pace of studies on microRNA regulation and function necessitates the development of suitable techniques for measuring and modulating microRNAs in different model systems. This review summarizes experimental strategies for microRNA research and highlights the strengths and weaknesses of different approaches. The development of more specific and sensitive assays will further illuminate the biology behind microRNAs and will advance opportunities to safely pursue them as therapeutic modalities.