Epigenetics and cyclooxygenase-2 mediate dysfunction in alveolar macrophages and polymorphonuclear neutrophils post-bone marrow transplantation by

A healthy and independent life requires skeletal muscles to maintain optimal function throughout the lifespan, which is in turn dependent on efficient activation of processes that regulate muscle development, homeostasis, and metabolism. Thus, identifying mechanisms that modulate these processes is of crucial priority. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have emerged as a class of previously unrecognized transcripts whose importance in a wide range of biological processes and human disease is only starting to be appreciated. In this review, we summarize the roles of recently identified miRNAs and lncRNAs during skeletal muscle development and pathophysiology. We also discuss several molecular mechanisms of these noncoding RNAs. Undoubtedly, further systematic understanding of these noncoding RNAs' functions and mechanisms will not only greatly expand our knowledge of basic skeletal muscle biology, but also significantly facilitate the development of therapies for various muscle diseases, such as muscular dystrophies, cachexia, and sarcopenia.

Copyright © 2015 Mao Nie et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A healthy and independent life requires skeletal muscles to maintain optimal function throughout the lifespan, which is in turn dependent on efficient activation of processes that regulate muscle development, homeostasis, and metabolism. Thus, identifying mechanisms that modulate these processes is of crucial priority. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have emerged as a class of previously unrecognized transcripts whose importance in a wide range of biological processes and human disease is only starting to be appreciated. In this review, we summarize the roles of recently identified miRNAs and lncRNAs during skeletal muscle development and pathophysiology. We also discuss several molecular mechanisms of these noncoding RNAs. Undoubtedly, further systematic understanding of these noncoding RNAs’ functions and mechanisms will not only greatly expand our knowledge of basic skeletal muscle biology, but also significantly facilitate the development of therapies for various muscle diseases, such as muscular dystrophies, cachexia, and sarcopenia. 1.

Yin Yang 1 (YY1), a ubiquitously expressed transcription factor, plays a critical role in regulating cell development, differ-entiation, cellular proliferation and tumorigenesis. Previous studies identified many YY1-regulated target genes in both human and mouse. Emerging global mapping by Chromatin ImmnoPrecipitation (ChIP)-based high-throughput experi-ments indicate that YY1 binds to a vast number of loci genome-wide. However, the information is widely scattered in many disparate poorly cross-indexed literatures; a large portion was only published recently by the ENCODE consortium with limited annotation. A centralized database, which annotates and organizes YY1-binding loci and target motifs in a systematic way with easy access, will be valuable resources for the research community. We therefore implemented a web-based YY1 Target loci Database (YY1TargetDB). This database contains YY1-binding loci (binding peaks) from ChIP-seq and ChIP-on-chip experiments, computationally predicated YY1 and cofactor motifs within each locus. It also collects the experimentally verified YY1-binding motifs from individual researchers. The current version of YY1TargetDB contains 92 314 binding loci identified by ChIP-based experiments; 157 200 YY1-binding motifs in which 42 are experi-

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With 550 000 new cases diagnosed annually and $37 billion spent per year,1 heart failure (HF) with reduced ejection frac-tion is one of the largest contributors to disease burden and healthcare expenditure in the United States. Despite signifi-cant progress in the treatment of HF2,3 with medications, the prognosis of HF remains dismal, with a mortality rate of 42% at 5 years after diagnosis. Therefore, understanding the under-lying molecular pathways in the transition from established cardiovascular disease to HF may spur the development of novel biomarkers and therapeutic targets. The heart responds to stressors such as hypoxia (in myocar-dial infarction [MI]), increased wall stress (in valvular heart disease), and neurohormonal/metabolic stress (in diabetes mellitus and hypertension) by cardiomyocyte hypertrophy and fibrosis. Although initially compensatory for increased wall stress or myocyte loss, the molecular pathways that underlie pathological hypertrophy are ultimately maladaptive, recapitulating further hypertrophy, contractile dysfunction, apoptosis, and fibrosis. The progression to HF is associated with a characteristic cascade of altered intracellular signaling and gene expression, representing a final common pathway to ultimate decompensation. The various signaling pathways that underlie pathological hypertrophy and the progression to HF have been the subject of intense investigation and are sum-marized in multiple review publications.4–9. More recently, considerable attention has been paid to microRNAs (miR-NAs), a novel biological control mechanism with the ability to regulate entire molecular networks by complex feedback and feed-forward mechanisms. Several reviews have summa-rized recent findings implicating miRNAs in cardiac develop-ment and disease.10,11 In the past few years, the discovery of circulating miRNAs has led to their investigation as biomark-ers and mediators of cell–cell communication. This review focuses on recent developments detailing the role of miRNAs in the pathogenesis of HF, their potential role as biomarkers, and their use as possible novel therapeutic targets. microRNAs: Novel and Potent