TP53, Tumor protein 53

  • 文章类型: Journal Article
    新技术的出现为工业和消费品中使用的各种化学品的兴起铺平了道路。这导致这些异源生物化合物在环境中的积累,其中它们对目标和非目标物种都构成严重威胁。miRNA是通过转录后调节基因表达与毒性相关的关键表观遗传机制之一。这里,我们提供了关于miRNA生物发生的全面观点,他们的作用机制,它们在异种生物毒性中的可能作用。Further,我们回顾了最近的体外和体内研究,涉及异种生物暴露诱导的miRNA改变和mRNA-miRNA相互作用。最后,我们解决了毒理学研究中与miRNA相关的挑战。
    The advent of new technologies has paved the rise of various chemicals that are being employed in industrial as well as consumer products. This leads to the accumulation of these xenobiotic compounds in the environment where they pose a serious threat to both target and non-target species. miRNAs are one of the key epigenetic mechanisms that have been associated with toxicity by modulating the gene expression post-transcriptionally. Here, we provide a comprehensive view on miRNA biogenesis, their mechanism of action and, their possible role in xenobiotic toxicity. Further, we review the recent in vitro and in vivo studies involved in xenobiotic exposure induced miRNA alterations and the mRNA-miRNA interactions. Finally, we address the challenges associated with the miRNAs in toxicological studies.
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  • 文章类型: Journal Article
    心力衰竭是一种预后不良的常见疾病,与心脏免疫细胞浸润和细胞因子表达失调有关。最近,造血细胞的克隆扩增与获得性(即,不可遗传)DNA突变,一个被称为克隆造血的过程,据报道与包括心力衰竭在内的心血管疾病有关。机制研究表明,携带这些体细胞突变的白细胞显示出改变的炎症特征,使实验模型中与心力衰竭相关的表型恶化。在这次审查中,我们总结了最近的流行病学和实验证据,这些证据支持克隆造血介导的免疫细胞功能障碍通常会导致心力衰竭和心血管疾病的假设。
    Heart failure is a common disease with poor prognosis that is associated with cardiac immune cell infiltration and dysregulated cytokine expression. Recently, the clonal expansion of hematopoietic cells with acquired (i.e., nonheritable) DNA mutations, a process referred to as clonal hematopoiesis, has been reported to be associated with cardiovascular diseases including heart failure. Mechanistic studies have shown that leukocytes that harbor these somatic mutations display altered inflammatory characteristics that worsen the phenotypes associated with heart failure in experimental models. In this review, we summarize recent epidemiological and experimental evidence that support the hypothesis that clonal hematopoiesis-mediated immune cell dysfunction contributes to heart failure and cardiovascular disease in general.
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  • 文章类型: Journal Article
    黑素瘤的发展和进展已归因于独立或组合的遗传和表观遗传事件。就遗传改变而言,在理解黑色素瘤的发病机理方面取得了显着进展。然而,最近的研究揭示了表观遗传机制在基因表达调控中的复杂参与,包括甲基化,染色质修饰和重塑,以及非编码RNA的多种活性。基因甲基化和miRNAs在黑色素瘤中的作用已经得到了相对较好的研究,但其他研究表明,染色质状态和长链非编码RNA差异表达的变化可导致关键基因调控的改变。一起来看,它们影响相互影响的信号通路的功能,相交,并形成局部扰动干扰整个系统活动的网络。这里,我们关注的是表观遗传事件如何与这些途径交织在一起,并有助于黑素瘤的分子发病机制.
    The development and progression of melanoma have been attributed to independent or combined genetic and epigenetic events. There has been remarkable progress in understanding melanoma pathogenesis in terms of genetic alterations. However, recent studies have revealed a complex involvement of epigenetic mechanisms in the regulation of gene expression, including methylation, chromatin modification and remodeling, and the diverse activities of non-coding RNAs. The roles of gene methylation and miRNAs have been relatively well studied in melanoma, but other studies have shown that changes in chromatin status and in the differential expression of long non-coding RNAs can lead to altered regulation of key genes. Taken together, they affect the functioning of signaling pathways that influence each other, intersect, and form networks in which local perturbations disturb the activity of the whole system. Here, we focus on how epigenetic events intertwine with these pathways and contribute to the molecular pathogenesis of melanoma.
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