Epigenetic control of exercise adaptations in the equine athlete: Current evidence and future directions.
- 作者列表："Denham J","McCluskey M","Denham MM","Sellami M","Davie AJ
:Horses (Equus ferus caballus) have evolved over the past 300 years in response to man-made selection for particular athletic traits. Some of the selected traits were selected based on the size and horses' muscular power (eg Clydesdales), whereas other breeds were bred for peak running performance (eg Thoroughbred and Arabian). Although the physiological changes and some of the cellular adaptations responsible for athletic potential of horses have been identified, the molecular mechanisms are only just beginning to be comprehensively investigated. The purpose of this review was to outline and discuss the current understanding of the molecular mechanisms underpinning the athletic performance and cardiorespiratory fitness in athletic breeds of horses. A brief review of the biology of epigenetics is provided, including discussion on DNA methylation, histone modifications and small RNAs, followed by a summary and critical review of the current work on the exercise-induced epigenetic and transcriptional changes in horses. Important unanswered questions and currently unexplored areas that deserve attention are highlighted. Finally, a rationale for the analysis of epigenetic modifications in the context with exercise-related traits and ailments associated with athletic breeds of horses is outlined in order to help guide future research.
: 马 (Equus ferus caballus) 在过去的300年中已经进化，以响应对特定运动特征的人为选择。一些选择的性状是根据大小和马的肌肉力量 (如Clydesdales) 选择的，而其他品种是为了达到最佳跑步性能而培育的 (如纯种马和阿拉伯品种)。虽然已经确定了与马的运动潜力有关的生理变化和一些细胞适应，但分子机制才刚刚开始全面研究。这篇综述的目的是概述和讨论目前对支持运动品种马的运动表现和心肺健康的分子机制的理解。提供了对表观遗传学生物学的简要回顾，包括对DNA甲基化、组蛋白修饰和小rna的讨论，随后对目前关于马的运动诱导的表观遗传和转录变化的工作进行了总结和评论。强调了值得关注的重要未回答的问题和目前尚未探索的领域。最后，概述了在与运动相关的性状和与马的运动品种相关的疾病的背景下分析表观遗传修饰的基本原理，以帮助指导未来的研究。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.