MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

Telocytes (TCs) are a novel interstitial (stromal) cell type described in many tissues and organs (www.telocytes.com). A TC is characterized by a small cell body (9-15 μm) and a variable number (one to five) of extremely long and thin telopodes (Tps), with alternating regions of podomers (∼80 nm) and podoms (250-300 nm). Tps are interconnected by homo- and heterocellular junctions and form three-dimensional networks. Moreover, Tps release three types of extracellular vesicles: exosomes, ectosomes, and multivesicular cargos, which are involved in paracrine signaling. Different techniques have been used to characterize TCs, from classical methods (light microscopy, electron microscopy) to modern 'omics'. It is considered that electron microscopy is essential for their identification, and CD34/PDGFRα double immunohistochemistry can orientate the diagnosis. Functional evidence is accumulating that TCs may be intimately involved in the maintenance of tissue homeostasis and renewal by short- and long-distance intercellular communication. This review focuses on the most recent findings regarding TC features and locations and the principal hypotheses about their functions in normal and diseased organs. TC involvement in regenerative medicine is also considered.

Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes. Conversely, inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified as two target genes of miR-433. Decreased level of AZIN1 activated TGF-β1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis. Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction. Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis.

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