Abstract-MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberrantly expressed in the vascular walls after balloon injury. The aberrantly expressed miRNAs were further confirmed by Northern blot and quantitative real-time polymerase chain reaction. Modulating an aberrantly overexpressed miRNA, miR-21, via antisense-mediated depletion (knock-down) had a significant negative effect on neointimal lesion formation. In vitro, the expression level of miR-21 in dedifferentiated vascular smooth muscle cells was significantly higher than that in fresh isolated differentiated cells. Depletion of miR-21 resulted in decreased cell proliferation and increased cell apoptosis in a dose-dependent manner. MiR-21-mediated cellular effects were further confirmed in vivo in balloon-injured rat carotid arteries. Western blot analysis demonstrated that PTEN and Bcl-2 were involved in miR-21-mediated cellular effects. The results suggest that miRNAs are novel regulatory RNAs for neointimal lesion formation. MiRNAs may be a new therapeutic target for proliferative vascular diseases such as atherosclerosis, postangioplasty restenosis, transplantation arteriopathy, and stroke. (Circ Res. 2007;100:1579-1588.)Key Words: microRNAs Ⅲ vascular smooth muscle cells Ⅲ proliferation Ⅲ apoptosis Ⅲ neointimal formation M icroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs of Ϸ22 nucleotides and constitute a novel class of gene regulators. [1][2][3] Although the first miRNA, lin-4, was discovered in 1993, 4,5 their presence in vertebrates was confirmed only in 2001. 6 MiRNAs are initially transcribed by RNA polymerase II (Pol II) in the nucleus to form large pri-miRNA transcripts. 7 The primiRNAs are processed by the RNase III enzymes, Drosha and Dicer, to generate 18-to 24-nucleotide mature miRNAs. The mature miRNAs negatively regulate gene expression in 1 of 2 ways that depend on the degree of complementarity between the miRNA and its target. MiRNAs that bind to 3ЈUTR of mRNA with imperfect complementarity block protein translation. In contrast, miRNAs that bind to mRNA with perfect complementarity induce targeted mRNA cleavage. Currently, more than 400 miRNAs have been cloned and sequenced in human, and the estimated number of miRNA genes is as high as 1000 in the human genome. 8,9 As a group, miRNAs are estimated to regulate 30% genes of the human genome. 10 Analogous to the first RNA revolution in the 1980s with Cech discovering the enzymatic activity of RNA, 11 this recent discovery of RNAi and miRNA may represent the second RNA revolution. 12 Small interfering RNAs (siRNAs) are another class of small noncoding RNAs that have similar mechanism for gene expression regulation. However, they are different from each other. 5,13 The chief difference lies in their origins....

MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate gene expression. Although miRNAs are highly expressed in the heart, their roles in heart diseases are currently unclear. Using microarray analysis designed to detect the majority of mammalian miRNAs identified thus far, we demonstrated that miRNAs are aberrantly expressed in hypertrophic mouse hearts. The time course of the aberrant miRNA expression was further identified in mouse hearts at 7, 14, and 21 days after aortic banding. Nineteen of the most significantly dysregulated miRNAs were further confirmed by Northern blot and/or real-time polymerase chain reaction, in which miR-21 was striking because of its more than fourfold increase when compared with the sham surgical group. Similar aberrant expression of the most up-regulated miRNA, miR-21, was also found in cultured neonatal hypertrophic cardiomyocytes stimulated by angiotensin II or phenylephrine. Modulating miR-21 expression via antisense-mediated depletion (knockdown) had a significant negative effect on cardiomyocyte hypertrophy. The results suggest that miRNAs are involved in cardiac hypertrophy formation. miRNAs might be a new therapeutic target for cardiovascular diseases involving cardiac hypertrophy such as hypertension, ischemic heart disease, valvular diseases, and endocrine disorders. (Am J

This place of death study includes more populations than any other known. In many populations, residential aged care was an important site of death for older people, indicating the need to optimise models of end-of-life care in this setting. For many countries, more standardised reporting of place of death would inform policies and planning of services to support end-of-life care.

Abstract-In this paper, we consider a wireless-powered cooperative communication network consisting of one hybrid accesspoint (AP), one source, and one relay. In contrast to conventional cooperative networks, the source and relay in the considered network have no embedded energy supply. They need to rely on the energy harvested from the signals broadcasted by the AP for their cooperative information transmission. Based on this three-node reference model, we propose a harvest-then-cooperate (HTC) protocol, in which the source and relay harvest energy from the AP in the downlink and work cooperatively in the uplink for the source's information transmission. Considering a delay-limited transmission mode, the approximate closed-form expression for the average throughput of the proposed protocol is derived over Rayleigh fading channels. Subsequently, this analysis is extended to the multi-relay scenario, where the approximate throughput of the HTC protocol with two popular relay selection schemes is derived. The asymptotic analyses for the throughput performance of the considered schemes at high signal-to-noise radio are also provided. All theoretical results are validated by numerical simulations. The impacts of the system parameters, such as time allocation, relay number, and relay position, on the throughput performance are extensively investigated.

BackgroundTo overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells.MethodsWe used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed.ResultsWe found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls.ConclusionTogether, our results demonstrate that hypoxic bladder cancer cells remodel tumor microenvironment to facilitate tumor growth and development though secreting the oncogenic lncRNA-UCA1-enriched exosomes and exosomal lncRNA-UCA1 in human serum has the possibility as a diagnostic biomarker for bladder cancer.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0714-8) contains supplementary material, which is available to authorized users.