Formation of skeletal muscle is among the most striking examples of cellular plasticity in animal tissue development, and while muscle progenitor cells are reprogrammed by epithelial-mesenchymal transition (EMT) to migrate during embryonic development, the regulation of EMT in post-natal myogenesis remains poorly understood. Here, we demonstrate that the long noncoding RNA (lncRNA) Meg3 regulates EMT in myoblast differentiation and skeletal muscle regeneration. Chronic inhibition of Meg3 in C2C12 myoblasts induced EMT, and suppressed cell state transitions required for differentiation. Furthermore, adenoviral Meg3 knockdown compromised muscle regeneration, which was accompanied by abnormal mesenchymal gene expression and interstitial cell proliferation. Transcriptomic and pathway analyses of Meg3-depleted C2C12 myoblasts and injured skeletal muscle revealed a significant dysregulation of EMT-related genes, and identified TGFβ as a key upstream regulator. Importantly, inhibition of TGFβR1 and its downstream effectors, and the EMT transcription factor Snai2, restored many aspects of myogenic differentiation in Meg3-depleted myoblasts in vitro. We further demonstrate that reduction of Meg3-dependent Ezh2 activity results in epigenetic alterations associated with TGFβ activation. Thus, Meg3 regulates myoblast identity to facilitate progression into differentiation.

Non-coding RNAs (ncRNAs) play a key role in the regulation of transcriptional and epigenetic activity in mammalian cells. Comprehensive analysis of these ncRNAs has revealed sophisticated gene regulatory mechanisms which finely tune the proper gene output required for cellular homeostasis, proliferation, and differentiation. However, this elaborate circuitry has also made it vulnerable to perturbations that often result in disease. Among the many types of ncRNAs, long non-coding RNAs (lncRNAs) appear to have the most diverse mechanisms of action including competitive binding to miRNA targets, direct binding to mRNA, interactions with transcription factors, and facilitation of epigenetic modifications. Moreover, many lncRNAs display tissue-specific expression patterns suggesting an important regulatory role in organogenesis, yet the molecular mechanisms through which these molecules regulate cardiac and skeletal muscle development remains surprisingly limited. Given the structural and metabolic similarities of cardiac and skeletal muscle, it is likely that several lncRNAs expressed in both of these tissues have conserved functions in establishing the striated muscle phenotype. As many aspects of regeneration recapitulate development, understanding the role lncRNAs play in these processes may provide novel insights to improve regenerative therapeutic interventions in cardiac and skeletal muscle diseases. This review highlights key lncRNAs that function as regulators of development, regeneration, and disease in cardiac and skeletal muscle. Finally, we highlight lncRNAs encoded by imprinted genes in striated muscle and the contributions of these loci on the regulation of gene expression.

A síndrome dos ovários policísticos (SOP) é a doença endócrina mais comum entre mulheres em idade reprodutiva e corresponde à principal causa de anovulação. Além de suas principais manifestações clínicas, a doença tem grande relação com hiperinsulinismo e resistência à insulina. Assim, tal associação entre SOP e resistência insulínica desencadeou a realização de estudos sobre o uso de metformina no tratamento da síndrome, tendo em vista sua ação comprovada como sensibilizador de insulina. METODOLOGIA: O estudo trata-se de uma revisão narrativa da literatura com objetivo de esclarecer o impacto do uso de metformina na SOP. RESULTADOS: Como referencial ao artigo, foram selecionados dez estudos de revisões, quatro ensaios clínicos, duas diretrizes, um estudo prospectivo e um manuscrito. DISCUSSÃO: O uso de metformina no tratamento da SOP apresentou resultados de significativa relevância, principalmente em pacientes com obesidade e hiperinsulinemia: a droga diminui Índice de Massa Corporal (IMC) e os níveis de insulina em jejum. Todavia, foi evidenciado que a metformina em comparação a outros medicamentos apresenta resultados mais baixos em taxa de ovulação. CONCLUSÃO: A metformina se mostrou eficaz como terapia combinada com Clomifene e Letrozol no tratamento da SOP, porém não houve um consenso quanto ao uso em monoterapia.

Introdução: Dado a incidência e importância do carcinoma hepatocelular a nível global, o objetivo deste artigo é realizar uma revisão integrativa sobre a abordagem desse tipo de neoplasia. Metodologia: Foram utilizados descritores inseridos no MeSH: “carcinoma hepatocelular”; “tratamento de doenças” e “procedimentos cirúrgicos operatórios''. Foi utilizado o operador boleano “AND” entre as combinações. Encontrou-se 46 artigos, com filtros: Free full text, Randomized Controlled Trial, nos últimos 10 anos, em humanos, com a linguagem em inglês, que foram publicados no MEDLINE e em pacientes com faixa etária entre 19 e 64 anos. Resultados: A radiofrequência foi relacionada a uma sobrevida geral e melhor tolerabilidade, e é recomendada para pacientes com reserva funcional hepática limitada. Foi visto que 61,6% dos pacientes tiveram cirrose hepática confirmada por histopatologia pós-operatória alguma complicação grave ou moderada com taxa de complicação esperada moderada de 27% para ressecções abertas e 13% para ressecções laparoscópicas. Discussão: A hepatectomia é a opção de primeira escolha para indivíduos com carcinoma hepatocelular, mas o prognóstico varia de cada paciente. Conclusão: A ressecção cirúrgica é a primeira linha de tratamento do CHC. Por sua vez, a radiofrequência é prevalecente para pacientes em que a ressecção cirúrgica é contraindicada.

Aging is a known contributor to cardiovascular dysfunction. It is well-established that with age there are functional changes in the heart; yet, the proteins responsible for maintaining sarcomere integrity are not well understood during the aging process. A key protein, cardiac myosin binding protein C (cMyBP-C), contributes to the structural integrity and the regulation of actomyosin interactions. To date, little is known about the effects of aging on cMyBP-C. Therefore, the first step in evaluating this sarcomere protein was to determine the expression of cMyBP-C in cardiac tissue across the lifespan. Using ten C57BL/6 male mice per age group (adult (6-7 months), old (22-25 months), and very old (≥29 months)), body and heart mass were determined. Next a portion of the cardiac tissue was homogenized, and protein concentration was determined (BCA assay). The protein samples were probed for cMyBP-C with MYBPC3 (Abcam, #ab133499) by Western Blot. One-way ANOVA was performed to evaluate differences between groups. Results indicated there was an increase in heart mass with age, but relative to body weight there was no significant difference between the three age groups. Western blot analysis revealed no significant age-related difference in the expression of cMyBP-C. Although there was no change in expression levels, it is not possible to rule out cMyBP-C as a contributor to age-related cardiac dysfunction because phosphorylation is known to play a critical role in the function of cMyBP-C. Thus, further investigation of the phosphorylation status of cMyBP-C is needed and is ongoing.