Search results for "mito"
showing 10 items of 2513 documents
Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury
2017
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…
Exercise training as a drug to treat age associated frailty
2016
Exercise causes an increase in the production of free radicals [1]. As a result of a hormetic mechanism antioxidant enzymes are synthesised and the cells are protected against further oxidative stress. Thus, exercise can be considered as an antioxidant [2]. Age-associated frailty is a major medical and social concern as it can easily lead to dependency. In this review we describe that oxidative stress is associated with frailty and the mechanism by which exercise prevents age-associated frailty. We propose that individually tailored multicomponent exercise programmes are one of the best ways to prevent and to treat age-associated frailty.
A Multi-Parametric Fluorescent Assay for the Screening and Mechanistic Study of Drug-Induced Steatosis in Liver Cells in Culture.
2017
Human hepatic cells have been used for drug safety risk evaluations throughout early development phases. They provide rapid, cost-effective early feedback to identify drug candidates with potential hepatotoxicity. This unit presents a cell-based assay to evaluate the risk of liver damage associated with steatogenic drugs. Detailed protocols for cell exposure to test compounds and for the assessment of steatosis-related cell parameters (intracellular lipid content, reactive oxygen species production, mitochondrial impairment, and cell death) are provided. A few representative results that illustrate the utility of this procedure for the screening of drug-induced steatosis are shown. © 2017 b…
Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.
2016
During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition…
Retinal homeobox promotes cell growth, proliferation and survival of mushroom body neuroblasts in the Drosophila brain.
2016
Abstract The Drosophila mushroom bodies, centers of olfactory learning and memory in the fly ‘forebrain’, develop from a set of neural stem cells (neuroblasts) that generate a large number of Kenyon cells (KCs) during sustained cell divisions from embryonic to late pupal stage. We show that retinal homeobox ( rx ), encoding for an evolutionarily conserved transcription factor, is required for proper development of the mushroom bodies. Throughout development rx is expressed in mushroom body neuroblasts (MBNBs), their ganglion mother cells (MB-GMCs) and young KCs. In the absence of rx function, MBNBs form correctly but exhibit a reduction in cell size and mitotic activity, whereas overexpress…
Mitochondrion at the Crossroad Between Nutrients and Epigenome.
2019
Epigenetic profile is the link between the regulation of nuclear gene expression and the environment. The most important factors capable of significantly affecting the cellular environment are the amount and quality of nutrients available. Mitochondria are both involved in the production of some of the molecules capable of directly affecting the epigenome and have a critical role in the conversion of nutrients into usable energy. Carbohydrate and fats are converted into ATP, acetyl-CoA, SAM, and NADH. These high-energy substrates are, in turn, capable of driving the epigenetic profile. We describe substances capable of affecting this mechanism. On the other hand, nutritional interventions c…
Maternal DNA lineages at the gate of Europe in the 10th century AD
2018
Given the paucity of archaeogenetic data available for medieval European populations in comparison to other historical periods, the genetic landscape of this age appears as a puzzle of dispersed, small, known pieces. In particular, Southeastern Europe has been scarcely investigated to date. In this paper, we report the study of mitochondrial DNA in 10th century AD human samples from Capidava necropolis, located in Dobruja (Southeastern Romania, Southeastern Europe). This geographical region is particularly interesting because of the extensive population flux following diverse migration routes, and the complex interactions between distinct population groups during the medieval period. We suc…
Higher physiopathogenicity byFasciola giganticathan by the genetically closeF. hepatica: experimental long-term follow-up of biochemical markers
2016
Background: Fascioliasis is caused by Fasciola hepatica and F. gigantica. The latter, always considered secondary in human infection, nowadays appears increasingly involved in Africa and Asia. Unfortunately, little is known about its pathogenicity, mainly due to difficulties in assessing the moment a patient first becomes infected and the differential diagnosis with F. hepatica. Methods: A long-term, 24-week, experimental study comparing F. hepatica and F. giganticawas made for the first time in the same animal model host, Guirra sheep. Serum biochemical parameters of liver damage, serum electrolytes, protein metabolism, plasma proteins, carbohydrate metabolism, hepatic lipid metabolism and…
Ancient goat genomes reveal mosaic domestication in the Fertile Crescent
2018
How humans got their goatsLittle is known regarding the location and mode of the early domestication of animals such as goats for husbandry. To investigate the history of the goat, Dalyet al.sequenced mitochondrial and nuclear sequences from ancient specimens ranging from hundreds to thousands of years in age. Multiple wild populations contributed to the origin of modern goats during the Neolithic. Over time, one mitochondrial type spread and became dominant worldwide. However, at the whole-genome level, modern goat populations are a mix of goats from different sources and provide evidence for a multilocus process of domestication in the Near East. Furthermore, the patterns described suppor…
Reconstructing the deep population history of Central and South America
2018
We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary sou…