糖尿病心肌病早期诊断指标的研究进展

随着糖尿病发病率的迅速增加,伴有心肌病的糖尿病患者数量也正以惊人的速度增长,然而目前对于糖尿病心肌病早期诊断的生化指标、辅助检查研究仍不充分。早期诊断糖尿病心肌病,对于疾病的防治及预后至关重要。现就糖尿病心肌病早期诊断指标的研究进展进行相关综述。     

miRNA在食管癌中的研究进展

我国是食管癌高发国家,发病人数占全球一半以上,国内食管癌的死亡率为17.38/10万,居恶性肿瘤的第4位。miRNA是新发现的一种具有高度进化保守性的单链RNA,在转录后水平引起靶mRNA降解或翻译抑制。miRNA的表达水平与食管癌的类型、预后等密切相关。在外周血中,miRNA水平也表现出显著的肿瘤相关性、组织特异性和表达稳定性。随着食管癌发病率不断增加,人们更加关注食管癌的发病机制及早期分子生物学标志物的研究。     

Five Freely Circulating miRNAs and Bone Tissue miRNAs Are Associated With Osteoporotic Fractures

Osteoporosis as a systemic skeletal disorder is characterized by increased bone fragility and the risk of fractures. According to the World Health Organization, osteoporosis is one of the 10 most common diseases and affects approximately 75 million people in Europe, the United States, and Japan. In this context, the identification of specific microRNA (miRNA) signatures is an important step for new diagnostic and therapeutic approaches. The focus of interest on miRNAs as biomarkers came with new publications identifying free circulating extracellular miRNAs associated with various types of cancer. This study aimed to identify specific miRNAs in patients with osteoporotic fractures compared with nonosteoporotic fractures. For the array analysis, miRNAs were isolated from the serum of 20 patients with hip fractures, transcribed, and the samples were pooled into 10 osteoporotic and 10 nonosteoporotic specimens. With each pool of samples, human serum and plasma miRNA PCR arrays were performed, which are able to identify 83 different miRNAs. Subsequently, a separate validation analysis of each miRNA found to be regulated in the array followed with miRNA samples isolated from the serum of 30 osteoporotic and 30 nonosteoporotic patients and miRNA samples isolated from the bone tissue of 20 osteoporotic and 20 nonosteoporotic patients. With the validation analysis of the regulated miRNAs, we identified 9 miRNAs, namely miR‐21, miR‐23a, miR‐24, miR‐93, miR‐100, miR‐122a, miR‐124a, miR‐125b, and miR‐148a, that were significantly upregulated in the serum of patients with osteoporosis. In the bone tissue of osteoporotic patients, we identified that miR‐21, miR‐23a, miR‐24, miR‐25, miR‐100, and miR‐125b displayed a significantly higher expression. A total of 5 miRNAs display an upregulation both in serum and bone tissue. This study reveals an important role for several miRNAs in osteoporotic patients and suggested that they may be used as biomarkers for diagnostic purposes and may be a target for treating bone loss and optimizing fracture healing in osteoporotic patients. © 2014 American Society for Bone and Mineral Research.     

Identification of microRNA expression signature for the diagnosis and prognosis of cervical squamous cell carcinoma

Cervical cancer is the fourth leading cause of cancer death among women globally. The prognosis of cervical cancer patients differs considerably, and clinical outcomes are difficult to predict. Given the significant roles of miRNAs in human cancers, identification of novel and reliable miRNA biomarkers is important for targeted cervical cancer therapy. In the present study, we aimed to reveal biological significance of miR-200a, miR-423, miR-34a, miR-193a, and miR-455 for the prognosis and diagnosis of cervical cancer and their association with the clinical outcomes of patients. Distinct expression profiles of miRNAs in formalin-fixed paraffin-embedded tissue samples of patients and healthy controls were evaluated using qRT-PCR. We identified miR-200a, miR-455, and miR-34a were significantly downregulated in cervical squamous cell carcinoma tissues compared to normal cervix tissue from healthy controls. Both miR-455 and miR-34a confer a promising diagnostic factor for the cervical cancer while miR-200a showed no significance in ROC analysis. Notably, low expression of miR-34a was markedly associated with the poor overall survival of cervical cancer patients as revealed by Kaplan-Meier survival analysis. Also, univariate and multivariate analysis indicated miR-34a expression as an independent prognostic factor. Consequently, our results underline the importance of distinct expression miRNAs in cervical squamous cell carcinoma.     

Downregulation of miR-9 correlates with poor prognosis in colorectal cancer

IntroductionmicroRNAs (miRNAs) are frequently dysregulated in many human cancers including colorectal cancer (CRC) and are useful candidate biomarkers in liquid biopsy of cancer for their stability in the blood.MethodsWe compared the expression of microRNA-9 (miR-9) in tissues (n = 357) and sera (n = 109) of CRC patients to determine whether miR-9 in serum reflects that in the cancer tissue in parallel. Also, we examined the miR-9 role in CRC by in vitro functional studies in four CRC cell lines.ResultsOn multivariate analysis of colorectal cancer tissues and sera, miR-9 low expressions were significantly associated pN stage (tissues; p < 0.01, serum; p = 0.013), and clinical stage (tissues; p < 0.01, serum; p = 0.031). Moreover, patients with low miR-9 expression had shorter survival than those with high miR-9 expression (log-rank test, tissue; p = 0.021, serum; p = 0.011). miR-9 level in serum reflects that in the tumor. The CRC cells with low miR-9 expression was significantly increased cell proliferation, migration, invasion and colony formation than cells with high miR-9 expression.ConclusionSerum miR-9 is an useful early detection marker in liquid biopsy of CRC and overexpression of miR-9 in CRC may be a novel prognostic marker as well.     

miRNA-519a在子宫内膜癌中的诊断及预后价值及机制探寻

目的利用TCGA数据库探寻miRNA-519a在子宫内膜癌中的诊断及预后价值及机制。方法通过对TCGA数据库中UCEC数据进行差异表达和生存分析,挑选出肿瘤组织中显著高表达且高表达提示预后不良的miRNA,并对该miRNA的靶基因进行富集分析,将富集出的关键通路中的mRNA与UCEC组织中低表达的mRNA交集,找出miRNA在UCEC中的靶基因和通路,并进一步利用双荧光素酶报告基因分析检测miRNA与靶基因mRNA的靶向结合进而调控其功能。结果TCGA-UCEC数据库中癌旁组织和癌组织存在不同miRNA差异表达,共148个miRNA上调,75个miRNA下调(|logFC|>2);进一步对差异表达miRNA进行预后分析发现,和正常组织相比,miRNA-519a在UCEC组织中显著高表达,且高表达的患者预后不良;通过mirDB数据库预测miRNA-519a靶基因(共685个),并用DAVID数据库将这些mRNA进行KEGG-PATHWAY富集分析,发现miRNA-519a的靶基因富集于肿瘤相关通路,且该通路相关基因中PDGFRA和TGFBR2在UCEC组织中显著低表达;双荧光素酶报告基因分析证明,miRNA-519a可与PDGFRA和TGFBR2 mRNA的3'-UTR直接结合并抑制两者的表达。结论miRNA-519a能够作为UCEC诊断和预后的生物标志物,miRNA-519a通过调控PDGFRA和TGFBR2的表达进而调控肿瘤的进程。     

miR-26b-5p通过抑制REST表达调节胶质瘤细胞生长和侵袭

目的探究miR-26b-5p通过抑制抑制元素1-沉默转录因子(repressor element 1-silencing transcrip-tion factor,REST)表达调节胶质瘤细胞生长和侵袭情况.方法逆转录-聚合酶链反应检测miR-26b-5p和REST表达水平;荧光素酶报告实验检测miR-26b-5p和REST的靶向关系;Hoechst染色检测细胞凋亡;Colony形成法检测细胞增殖;Transwell检测细胞侵袭;蛋白免疫印迹检测细胞Ki67、MMP-9、cleaved caspase-3蛋白表达水平.结果miR-26b-5p和REST存在直接靶向作用关系,与Control组比较,mimic组细胞增殖数、侵袭数和Ki67、MMP-9表达明显降低,凋亡率与cleaved caspase-3表达明显升高,inhibitor组细胞增殖数、侵袭数和Ki67、MMP-9表达明显升高,凋亡率与cleaved caspase-3表达明显降低.结论miR-26b-5p可以通过抑制对REST的表达调节胶质瘤细胞生长、侵袭、凋亡能力.     

A familial case of overgrowth syndrome caused by a 9q22.3 microdeletion in a mother and daughter

Microdeletions in the 9q22.3 chromosomal region can cause macrosomia with characteristic features, including prenatal-onset overgrowth, metopic craniosynostosis, hydrocephalus, developmental delay, and intellectual disability, in addition to manifestations of nevoid basal cell carcinoma syndrome (NBCCS). Haploinsufficiency of PTCH1 may be responsible for accelerated overgrowth, but the mechanism of macrosomia remains to be elucidated. We report a familial case with a 9q22.3 microdeletion, manifesting with prenatal-onset overgrowth in a mother and post-natal overgrowth in her daughter. Although both were clinically diagnosed with NBCCS, they had characteristic features of 9q22.3 microdeletion, especially the daughter. Microarray comparative genomic hybridization analysis revealed a 4.0 Mb deletion of chromosome 9q22.3 in both individuals. Among the 11 reported patients of overgrowth and/or macrosomia, a 550 Kb region encompassing PTCH1, C9orf3, FANCC, and 5 miRNAs is the most commonly deleted region. The let-7 family miRNAs, which are involved in diverse cellular processes including growth and tumor processes, were identified in the deleted regions in 10 of 11 patients. Characteristic features of 9q22.3 microdeletion might be associated with decreased expression of let-7.     

外泌体在骨不连治疗中的作用机制及进展

文题释义：外泌体：是细胞外囊泡小体,由不同类型的细胞释放,根据其自身各种特性,可运用于损伤组织间药物的传递,作为生物标志物,介导细胞间信息交流等巨大作用。 哺乳动物雷帕霉素靶蛋白信号通路：哺乳动物雷帕霉素靶蛋白(mTOR)是一种蛋白激酶,其催化亚单位是2种生化上截然不同的复合物mTORC1和mTORC2,对骨形成的调节非常重要。背景：骨不连是骨折术后常见的并发症,给患者带来了极大的困扰。随着外泌体技术的不断研发,外泌体在骨不连的治疗中逐渐显露优势,成为医疗工作新的研究方向。 目的：从国内外研究中归纳总结,探讨外泌体在骨不连治疗中的作用。 方法：中文以“外泌体,骨不连,骨重塑,骨再生,血管损伤,成骨细胞,破骨细胞”检索万方、中国知网、维普文献数据2003至2019年的相关文献,英文以“exosomes,nonunion,bone remodelling”,检索PubMed数据库2003至2019年的相关文献,根据纳入及排除标准摘选50篇文章。结果与结论：①近年来,外泌体作用于骨不连的研究得到越来越多的重视,外泌体中的miRNA及蛋白质可以通过影响骨细胞的分化作用于骨不连;②随着进一步的研究发现,外泌体可通过调节骨重塑,促进血管修复,改善系统性疾病等方面治疗骨不连;③但是目前对于外泌体的研究仍处于实验阶段,如何将其更好地应用于临床治疗还需进一步的探究。ORCID: 0000-0003-0172-7642(赖渝) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程