Ferroptosis: A missing puzzle piece in the p53 blueprint?
Ontology highlight
ABSTRACT:
SUBMITTER: Wang SJ
PROVIDER: S-EPMC4909446 | biostudies-other | 2016 May
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundAberrant metabolism is recognized as a hallmark of cancer, a pillar necessary for cellular proliferation. Regarding bioenergetics (ATP generation), most cancers display a preference not only toward aerobic glycolysis ("Warburg effect") and glutaminolysis (mitochondrial substrate level-phosphorylation) but also toward other metabolites such as lactate, pyruvate, and fat-derived sources. These secondary metabolites can assist in proliferation but cannot fully cover ATP demands.Scope of reviewThe concept of a static metabolic profile is challenged by instances of heterogeneity and flexibility to meet fuel/anaplerotic demands. Although metabolic therapies are a promising tool to improve therapeutic outcomes, either via pharmacological targets or press-pulse interventions, metabolic plasticity is rarely considered. Lack of bioenergetic analysis in vitro and patient-derived models is hindering translational potential. Here, we review the bioenergetics of cancer and propose a simple analysis of major metabolic pathways, encompassing both affordable and advanced techniques. A comprehensive compendium of Seahorse XF bioenergetic measurements is presented for the first time.Major conclusionsStandardization of principal readouts might help researchers to collect a complete metabolic picture of cancer using the most appropriate methods depending on the sample of interest.
| S-EPMC8637646 | biostudies-literature
Project description:Inactivation of the transcriptional regulator PhoP results in Mycobacterium tuberculosis attenuation. Preclinical testing has shown that attenuated M. tuberculosis phoP mutants hold promise as safe and effective live vaccine candidates. We focused this study to decipher the virulence networks regulated by PhoP. A combined transcriptomic and proteomic analysis revealed that PhoP controls a variety of functions including: hypoxia response through DosR crosstalking, respiratory metabolism, secretion of the major T-cell antigen ESAT-6, stress response, synthesis of pathogenic lipids and the M. tuberculosis persistence through transcriptional regulation of the enzyme isocitrate lyase. We also demonstrate that the M. tuberculosis phoP mutant SO2 exhibits an antigenic capacity similar to that of the BCG vaccine. Finally, we provide evidence that the SO2 mutant persists better in mouse organs than BCG. Altogether, these findings indicate that PhoP orchestrates a variety of functions implicated in M. tuberculosis virulence and persistence, making phoP mutants promising vaccine candidates.
| S-EPMC2566814 | biostudies-literature
Project description:We compare miRNA profiling in two cell populations of mesenchymal stromal cells focusing on senescence-related changes: Human Dental Pulp Stromal Cells (hDPSCs) and human Periosteum-Derived Progenitor Cells (hPDPCs). After these cells were harvested, total RNA extraction and whole genome miRNA profiling was performed, and DIANA-miRPath analysis was applied to find the target/pathways. Our finding is consistent with the idea that the embryological origin influences cell behavior and the ageing process. Moreover, the two populations activate different downstream mechanisms. Our study strengthens the hypothesis that ageing is driven by numerous mediators interacting through an intricate molecular network, which affects adult stem cells self-renewal capability.
2020-11-18 | GSE161688 | GEO
Project description:A 65-year-old man presented with acute decompensated heart failure. He was found to have severe prosthetic aortic valve regurgitation caused by a fractured strut of a sutureless prosthetic aortic valve that embolized to the distal portion of the aorta. We highlight the importance of multimodality imaging in diagnosis and management. (Level of Difficulty: Intermediate.).
| S-EPMC9270610 | biostudies-literature
Project description:Phosphorus (P) is a finite and dwindling resource. Debate focuses on current production and use of phosphate rock rather than on the amounts of P required in the future to feed the world. We applied a two-pool soil P model to reproduce historical continental crop P uptake as a function of P inputs from fertilizer and manure and to estimate P requirements for crop production in 2050. The key feature is the consideration of the role of residual soil P in crop production. Model simulations closely fit historical P uptake for all continents. Cumulative inputs of P fertilizer and manure for the period 1965-2007 in Europe (1,115 kg . ha(-1) of cropland) grossly exceeded the cumulative P uptake by crops (360 kg ha(-1)). Since the 1980s in much of Europe, P application rates have been reduced, and uptake continues to increase due to the supply of plant-available P from residual soil P pool. We estimate that between 2008 and 2050 a global cumulative P application of 700-790 kg . ha(-1) of cropland (in total 1,070-1,200 teragrams P) is required to achieve crop production according to the various Millennium Ecosystem Assessment scenarios [Alcamo J, Van Vuuren D, Cramer W (2006) Ecosystems and Human Well-Being: Scenarios, Vol 2, pp 279-354]. We estimate that average global P fertilizer use must change from the current 17.8 to 16.8-20.8 teragrams per year in 2050, which is up to 50% less than other estimates in the literature that ignore the role of residual soil P.
| S-EPMC3341047 | biostudies-other
Project description:The primary aim of this study was to determine the relationship between a team numerical advantage during structured phases of play and match event outcomes in professional Australian football. The secondary aim was to quantify how players occupy different sub-areas of the playing field in match play, while accounting for match phase and ball location. Spatiotemporal player tracking data and play-by-play event data from professional players and teams were collected from the 2019 Australian Football League season played at a single stadium. Logistic regression analysed the relationship between total players and team numerical advantage during clearances and inside 50's. Total players and team numerical advantage were also quantified continuously throughout a match, which were separated into three match phases (offence, defence, and stoppage) and four field positions (defensive 50, defensive midfield, attacking midfield, and forward 50). Results identified an increased team numerical advantage produced a greater likelihood of gaining possession from clearances or generating a score from inside 50's. Although, an increased number of total players inside 50 was likely associated with a concomitant decrease in the probability of scoring, irrespective of a team numerical advantage. Teams were largely outnumbered when the ball was in their forward 50 but attained a numerical advantage when the ball was in the defensive 50.
| S-EPMC8284792 | biostudies-literature
Project description:Several recent studies have found a conserved microRNA (miRNA) family, the miR-34s, to be direct transcriptional targets of p53. miR-34 activation can recapitulate elements of p53 activity, including induction of cell-cycle arrest and promotion of apoptosis, and loss of miR-34 can impair p53-mediated cell death. These data reinforce the growing awareness that non-coding RNAs are key players in tumour development by placing miRNAs in a central role in a well-known tumour-suppressor network.
| S-EPMC4053212 | biostudies-literature
Project description:Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care.
| S-EPMC8713157 | biostudies-literature
Project description:OBJECTIVES:The causes of the large and persistent Black-White disparity in preterm birth (PTB) are unknown. It is biologically plausible that chronic stress across a woman's life course could be a contributor. Prior research suggests that chronic worry about experiencing racial discrimination could affect PTB through neuroendocrine, vascular, or immune mechanisms involved in both responses to stress and the initiation of labor. This study aimed to examine the role of chronic worry about racial discrimination in Black-White disparities in PTB. METHODS:The data source was cross-sectional California statewide-representative surveys of 2,201 Black and 8,122 White, non-Latino, U.S.-born postpartum women with singleton live births during 2011-2014. Chronic worry about racial discrimination (chronic worry) was defined as responses of "very often" or "somewhat often" (vs. "not very often" or "never") to the question: "Overall during your life until now, how often have you worried that you might be treated or viewed unfairly because of your race or ethnic group?" Prevalence ratios (PRs) with 95% Confidence Intervals (CI) were calculated from sequential logistic regression models, before and after adjustment for multiple social/demographic, behavioral, and medical factors, to estimate the magnitude of: (a) PTB risks associated with chronic worry among Black women and among White women; and (b) Black-White disparities in PTB, before and after adjustment for chronic worry. RESULTS:Among Black and White women respectively, 36.9 (95% CI 32.9-40.9) % and 5.5 (95% CI 4.5-6.5) % reported chronic worry about racial discrimination; rates were highest among Black women of higher income and education levels. Chronic worry was significantly associated with PTB among Black women before (PR 1.73, 95% CI 1.12-2.67) and after (PR 2.00, 95% CI 1.33-3.01) adjustment for covariates. The unadjusted Black-White disparity in PTB (PR 1.59, 95%CI 1.21-2.09) appeared attenuated and became non-significant after adjustment for chronic worry (PR 1.30, 95% CI 0.93-1.81); it appeared further attenuated after adding the covariates (PR 1.17, 95% CI 0.85-1.63). CONCLUSIONS:Chronic worry about racial discrimination may play an important role in Black-White disparities in PTB and may help explain the puzzling and repeatedly observed greater PTB disparities among more socioeconomically-advantaged women. Although the single measure of experiences of racial discrimination used in this study precluded examination of the role of other experiences of racial discrimination, such as overt incidents, it is likely that our findings reflect an association between one or more experiences of racial discrimination and PTB. Further research should examine a range of experiences of racial discrimination, including not only chronic worry but other psychological and emotional states and both subtle and overt incidents as well. These dramatic results from a large statewide-representative study add to a growing-but not widely known-literature linking racism-related stress with physical health in general, and shed light on the links between racism-related stress and PTB specifically. Without being causally definitive, this study's findings should stimulate further research and heighten awareness of the potential role of unmeasured social variables, such as diverse experiences of racial discrimination, in racial disparities in health.
| S-EPMC5636124 | biostudies-literature
Project description:Puzzle pieces have become ubiquitous symbols for autism. However, puzzle-piece imagery stirs debate between those who support and those who object to its use because they believe puzzle-piece imagery evokes negative associations. Our study empirically investigated whether puzzle pieces evoke negative associations in the general public. Participants' ( N?=?400) implicit negative associations were measured with an Implicit Association Task, which is a speeded categorization task, and participants' explicit associations were measured with an Explicit Association Task, which is a standard task for assessing consumers' explicit associations with brands (and images of those brands). Puzzle pieces, both those used as autism logos and those used more generically, evoked negative implicit associations ( t(399)?=?-5.357, p?<?0.001) and negative explicit associations ( z?=?4.693, p?<?0.001, d?=?0.491). Participants explicitly associated puzzle pieces, even generic puzzle pieces, with incompleteness, imperfection, and oddity. Our results bear public policy implications. If an organization's intention for using puzzle-piece imagery is to evoke negative associations, our results suggest the organization's use of puzzle-piece imagery is apt. However, if the organization's intention is to evoke positive associations, our results suggest that puzzle-piece imagery should probably be avoided.
| S-EPMC6085079 | biostudies-literature