Genomic analysis of microRNA time-course expression in liver of mice treated with genotoxic carcinogen N-ethyl-N-nitrosourea

<p>Abstract</p> <p>Background</p> <p>Dysregulated expression of microRNAs (miRNAs) has been previously observed in human cancer tissues and shown promise in defining tumor status. However, there is little information as to if or when expression changes of miRNAs occur in normal tissues after carcinogen exposure.</p> <p>Results</p> <p>To explore the possible time-course changes of miRNA expression induced by a carcinogen, we treated mice with one dose of 120 mg/kg <it>N</it>-ethyl-<it>N</it>-nitrosourea (ENU), a model genotoxic carcinogen, and vehicle control. The miRNA expression profiles were assessed in the mouse livers in a time-course design. miRNAs were isolated from the livers at days 1, 3, 7, 15, 30 and 120 after the treatment and their expression was determined using a miRNA PCR Array. Principal component analysis of the miRNA expression profiles showed that miRNA expression at post-treatment days (PTDs) 7 and 15 were different from those at the other time points and the control. The number of differentially expressed miRNAs (DEMs) changed over time (3, 5, 14, 32, 5 and 5 at PTDs 1, 3, 7, 15, 30 and 120, respectively). The magnitude of the expression change varied with time with the highest changes at PTDs 7 or 15 for most of the DEMs. In silico functional analysis of the DEMs at PTDs 7 and 15 indicated that the major functions of these ENU-induced DEMs were associated with DNA damage, DNA repair, apoptosis and other processes related to carcinogenesis.</p> <p>Conclusion</p> <p>Our results showed that many miRNAs changed their expression to respond the exposure of the genotoxic carcinogen ENU and the number and magnitude of the changes were highest at PTDs 7 to 15. Thus, one to two weeks after the exposure is the best time for miRNA expression sampling.</p

Dinâmica não-linear e exercício físico: conceitos e aplicações Non-linear dynamics and physical exercise: concepts and applications

Médicos, fisiologistas, bioquímicos, psicólogos e até profissionais envolvidos com exercício físico estão recentemente aumentando seus interesses pela dinâmica não-linear, uma teoria científica desenvolvida principalmente por matemáticos, que é genericamente conhecida por Teoria da Complexidade. Embora poucos trabalhos em Educação Física e Esporte utilizem esse paradigma para solucionar seus problemas, nota-se um crescente interesse por esse mesmo enfoque, principalmente em relação aos efeitos do exercício físico sobre mudanças na variabilidade e complexidade de séries temporais fisiológicas. Geralmente, tais mudanças se revelam na forma de queda em seu comportamento temporal, denotando diminuição na complexidade do organismo ou de componentes envolvidos especificamente na sua regulação. De acordo com a Teoria da Complexidade, por enfatizar interações não-lineares existentes em sistemas biológicos, verifica-se que não é importante apenas a elevação (supercompensação) de componentes do organismo com a prática de exercícios físicos, mas também aqueles que atrofiam (descompensação) paralelamente, porque podem contribuir para a ocorrência de perda de sincronia na funcionalidade desses sistemas. Assim, em oposição à ênfase que se dá no treinamento físico à repetição monótona de atividade física intensa e voltada para efeitos específicos positivos, que invariavelmente leva à simplificação do organismo, recomenda-se maior variação qualitativa e quantitativa nos exercícios praticados. O objetivo é preservar sua complexidade natural ou impedir que ocorra diminuição rápida com o envelhecimento. A presente revisão tem por objetivo, além de descrever a possível perda de complexidade com o treinamento físico, discutir alguns conceitos da Teoria da Complexidade de modo introdutório, com particular ênfase em tópicos envolvendo saúde e desempenho físico.<br>Physicians, physiologists, biochemists, psychologists and even professionals involved with physical exercise have been recently increasing their interests for the non-linear dynamics, a scientific theory developed mainly by mathematicians, which is generically known as the Complexity Theory. Although few investigations on Physical Education and Sports make use of this paradigm to solve their problems, a growing interest for this very approach has been noticed, mainly concerning the effects of physical exercise on changes in the variability and complexity of physiological temporal series. Usually, such changes appear as the decrease in its temporal behavior, denoting in decrease in the body complexity or in the components specifically involved in its regulation. According to the Complexity Theory, since non-linear interactions existing in biological systems are emphasized, it is observed that not only the increase (overcompensation) of the body components with the practice of physical exercises but also those which cause atrophy (decompensation) in parallel, once they can compromise the functionality of these systems. Thus, contrary to the emphasis that is given in the physical training to the monotonous repetition of intense physical activity and with emphasis on positive specific effects, that invariably promote the simplification of the body, larger qualitative and quantitative variation is recommended in the exercise practice. The objective is to preserve its natural complexity or neutralize its rapid decrease with aging. The present review has the objective, besides describing the possible complexity loss with physical training, to discuss some concepts of the Complexity Theory in an introductory way, with particular emphasis on issues involving health and physical training