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Metabolism and epigenetics

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https://www.readbyqxmd.com/read/28315358/isocitrate-dehydrogenase-idh-inhibition-as-treatment-of-myeloid-malignancies-progress-and-future-directions
#1
REVIEW
Vivek A Upadhyay, Andrew M Brunner, Amir T Fathi
Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme. Over the last two decades, there has been a growing focus on the metabolic derangements that occur with IDH1 and IDH2 mutations. The altered IDH protein leads to accumulation of 2-hydroxyglutarate (2-HG), a metabolite with oncogenic activity via epigenetic mechanisms. The advent of IDH inhibitors has engendered hope in novel and targeted therapies in IDH1/2 mutant myeloid malignancies. We here summarize the basic physiology of IDH, the metabolic and oncogenic consequences of mutant IDH1/2, and the clinical significance of IDH inhibition in hematologic malignancies...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315153/effects-of-histone-deacetylase-inhibitory-prodrugs-on-epigenetic-changes-and-dna-damage-response-in-tumor-and-heart-of-glioblastoma-xenograft
#2
Nataly Tarasenko, Abraham Nudelman, Gabriela Rozic, Suzanne M Cutts, Ada Rephaeli
The histone deacetylase (HDAC) inhibitory prodrugs of butyric (AN7) and valproic (AN446) acids, which release the active acids upon metabolic degradation, were studied examining their differential effects on the viability, HDAC inhibitory activity and the DNA damage response (DDR), in glioblastoma cell and normal human astrocytes (NHAs). In xenografts of glioblastoma, AN7 or AN446 given or the combination of each of them with Dox augmented the anticancer activity of Dox and protected the heart from its toxicity...
March 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28314870/perillyl-alcohol-a-pleiotropic-natural-compound-suitable-for-brain-tumor-therapy-targets-free-radicals
#3
REVIEW
Aline C Gomes, Angélica L Mello, Manuel G Ribeiro, Diogo G Garcia, Clovis O Da Fonseca, Marcela D'Alincourt Salazar, Axel H Schönthal, Thereza Quirico-Santos
Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis...
March 17, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28314754/kdm6b-regulates-cartilage-development-and-homeostasis-through-anabolic-metabolism
#4
Jun Dai, Dongsheng Yu, Yafei Wang, Yishan Chen, Heng Sun, Xiaolei Zhang, Shouan Zhu, Zongyou Pan, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang
OBJECTIVES: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms. METHODS: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic Col2a1-CreER(T2);Kdm6b(f/f) ...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28302867/an-early-life-hypoxia-event-has-a-long-term-impact-on-protein-digestion-and-growth-in-european-sea-bass-juvenile
#5
José L Zambonino-Infante, David Mazurais, A Servili, C Cahu, G Vanderplancke, N Le Bayon, C Huelvan, Guy Claireaux
Ocean warming, eutrophication and consequent decrease in oxygen lead to smaller average fish size. Although such responses are well-known in an evolutionary context, involving multiple generations, it appears to be incompatible with current rapid environmental change. Rather, phenotypic plasticity could provide a means for marine fish to cope with rapid environmental changes. However, little is known about the mechanisms underlying plastic responses to environmental conditions that favour small phenotypes.Our aim was to investigate how and why European sea bass that had experienced a short episode of moderate hypoxia during their larval stage subsequently exhibited a growth depression at the juvenile stage compared to the control group...
March 16, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28301983/applying-systems-biology-methodology-to-identify-genetic-factors-possibly-associated-with-recovery-after-traumatic-brain-injury
#6
Brad G Kurowski, Amery Treble-Barna, Alexis J Pitzer, Shari L Wade, Lisa J Martin, Ranjit S Chima, Anil Jegga
Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality worldwide. It is linked with a number of medical, neurological, cognitive, and behavioral sequelae. The influence of genetic factors on the biology and related recovery after TBI is poorly understood. Studies that seek to elucidate the impact of genetic influences on neurorecovery after TBI will lead to better individualization of prognosis and inform development of novel treatments, which are considerably lacking. Current genetic studies related to TBI have focused on specific candidate genes...
March 16, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28298479/cyst-nematode-parasitism-induces-dynamic-changes-in-the-root-epigenome
#7
Tarek Hewezi, Thomas Lane, Sarbottam Piya, Aditi Rambani, J Hollis Rice, Meg Staton
A growing body of evidence indicates that epigenetic modifications can provide efficient, dynamic, and reversible cellular responses to a wide range of environmental stimuli. However, the significance of epigenetic modifications in plant-pathogen interactions remains largely unexplored. In this study, we provide a comprehensive analysis of epigenome changes during the compatible interaction between the beet cyst nematode Heterodera schachtii and Arabidopsis (Arabidopsis thaliana). Whole genome bisulfite sequencing was conducted to assess the dynamic changes in the methylome of Arabidopsis roots in response to H schachtii infection...
March 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28296592/ethanol-extract-of-capsella-bursa-pastoris-improves-hepatic-steatosis-through-inhibition-of-histone-acetyltransferase-activity
#8
Hyo-Kyoung Choi, Eun Ju Shin, Su Jin Park, Haeng Jeon Hur, Jae Ho Park, Min-Yu Chung, Myung Sunny Kim, Jin-Taek Hwang
Histone lysine acetylation is thought to play a role in regulating the balance between energy storage and energy expenditure. However, the epigenetic mechanisms by which food phytochemicals influence metabolic processes in the liver have not been thoroughly investigated. In this study, we investigated the effect of an ethanol extract of Capsella bursa-pastoris (ECB) on histone acetyltransferase (HAT) inhibition, and whether it could thereby attenuate lipid accumulation in vitro and in vivo. We observed that ECB inhibits HAT activity as assessed by colorimetric and autoradiography assay systems...
March 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28291256/exercise-rescues-obese-mothers-insulin-sensitivity-placental-hypoxia-and-male-offspring-insulin-sensitivity
#9
Denise S Fernandez-Twinn, Geraldine Gascoin, Barbara Musial, Sarah Carr, Daniella Duque-Guimaraes, Heather L Blackmore, Maria Z Alfaradhi, Elena Loche, Amanda N Sferruzzi-Perri, Abigail L Fowden, Susan E Ozanne
The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28290496/transcriptome-analysis-of-a-wild-bird-reveals-physiological-responses-to-the-urban-environment
#10
Hannah Watson, Elin Videvall, Martin N Andersson, Caroline Isaksson
Identifying the molecular basis of environmentally induced phenotypic variation presents exciting opportunities for furthering our understanding of how ecological processes and the environment can shape the phenotype. Urban and rural environments present free-living organisms with different challenges and opportunities, which have marked consequences for the phenotype, yet little is known about responses at the molecular level. We characterised transcriptomes from an urban and a rural population of great tits Parus major, demonstrating striking differences in gene expression profiles in both blood and liver tissues...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289216/b-vitamins-attenuate-the-epigenetic-effects-of-ambient-fine-particles-in-a-pilot-human-intervention-trial
#11
Jia Zhong, Oskar Karlsson, Guan Wang, Jun Li, Yichen Guo, Xinyi Lin, Michele Zemplenyi, Marco Sanchez-Guerra, Letizia Trevisi, Bruce Urch, Mary Speck, Liming Liang, Brent A Coull, Petros Koutrakis, Frances Silverman, Diane R Gold, Tangchun Wu, Andrea A Baccarelli
Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4(+) T-helper cells...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28289190/ampk-blocks-starvation-inducible-transgenerational-defects-in-caenorhabditis-elegans
#12
Emilie Demoinet, Shaolin Li, Richard Roy
Life history events, such as traumatic stress, illness, or starvation, can influence us through molecular changes that are recorded in a pattern of characteristic chromatin modifications. These modifications are often associated with adaptive adjustments in gene expression that can persist throughout the lifetime of the organism, or even span multiple generations. Although these adaptations may confer some selective advantage, if they are not appropriately regulated they can also be maladaptive in a context-dependent manner...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28283292/mixture-specific-gene-expression-in-zebrafish-danio-rerio-embryos-exposed-to-perfluorooctane-sulfonic-acid-pfos-perfluorohexanoic-acid-pfhxa-and-3-3-4-4-5-pentachlorobiphenyl-pcb126
#13
Mélanie Blanc, Anna Kärrman, Petr Kukucka, Nikolai Scherbak, Steffen Keiter
Perfluorooctane sulfonic acid (PFOS) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways...
March 7, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28281439/epigenetic-phosphorylation-control-of-mycobacterium-tuberculosis-infection-and-persistence
#14
Melissa Richard-Greenblatt, Yossef Av-Gay
Reversible protein phosphorylation is the most common type of epigenetic posttranslational modification in living cells used as a major regulation mechanism of biological processes. The Mycobacterium tuberculosis genome encodes for 11 serine/threonine protein kinases that are responsible for sensing environmental signals to coordinate a cellular response to ensure the pathogen's infectivity, survival, and growth. To overcome killing mechanisms generated within the host during infection, M. tuberculosis enters a state of nonreplicating persistence that is characterized by arrested growth, limited metabolic activity, and phenotypic resistance to antimycobacterial drugs...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28281142/role-of-dna-methylation-in-imprinting-disorders-an-updated-review
#15
REVIEW
Amr Rafat Elhamamsy
Genomic imprinting is a complex epigenetic process that contributes substantially to embryogenesis, reproduction, and gametogenesis. Only small fraction of genes within the whole genome undergoes imprinting. Imprinted genes are expressed in a monoallelic parent-of-origin-specific manner, which means that only one of the two inherited alleles is expressed either from the paternal or maternal side. Imprinted genes are typically arranged in clusters controlled by differentially methylated regions or imprinting control regions...
March 9, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28277977/human-liver-epigenetic-alterations-in-non-alcoholic-steatohepatitis-are-related-to-insulin-action
#16
Vanessa D de Mello, Ashok Matte, Alexander Perfilyev, Ville Männistö, Tina Rönn, Emma Nilsson, Pirjo Käkelä, Charlotte Ling, Jussi Pihlajamäki
Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5±7.7 years, BMI: 43±5.7 kg/m(2), type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated...
February 23, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28276448/blood-dna-methylation-pattern-is-altered-in-mesial-temporal-lobe-epilepsy
#17
Hong-Yu Long, Li Feng, Jin Kang, Zhao-Hui Luo, Wen-Biao Xiao, Li-Li Long, Xiao-Xin Yan, Luo Zhou, Bo Xiao
Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder; little is known whether it is associated with peripheral epigenetic changes. Here we compared blood whole genomic DNA methylation pattern in MTLE patients (n = 30) relative to controls (n = 30) with the Human Methylation 450 K BeadChip assay, and explored genes and pathways that were differentially methylated using bioinformatics profiling. The MTLE and control groups showed significantly different (P < 1.03e-07) DNA methylation at 216 sites, with 164 sites involved hyper- and 52 sites hypo- methylation...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275132/impact-of-polyunsaturated-and-saturated-fat-overfeeding-on-the-dna-methylation-pattern-in-human-adipose-tissue-a-randomized-controlled-trial
#18
Alexander Perfilyev, Ingrid Dahlman, Linn Gillberg, Fredrik Rosqvist, David Iggman, Petr Volkov, Emma Nilsson, Ulf Risérus, Charlotte Ling
Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses.Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial.Design: We studied the effects of 7 wk of excessive SFA (n = 17) or PUFA (n = 14) intake (+750 kcal/d) on the DNA methylation of ∼450,000 sites in human subcutaneous adipose tissue...
March 8, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28273874/early-life-nutritional-programming-of-type-2-diabetes-experimental-and-quasi-experimental-evidence
#19
REVIEW
Alexander M Vaiserman
Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies ('natural experiments'). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world...
March 5, 2017: Nutrients
https://www.readbyqxmd.com/read/28273478/epigenetic-mechanisms-of-transmission-of-metabolic-disease-across-generations
#20
REVIEW
Vicencia Micheline Sales, Anne C Ferguson-Smith, Mary-Elizabeth Patti
Both human and animal studies indicate that environmental exposures experienced during early life can robustly influence risk for adult disease. Moreover, environmental exposures experienced by parents during either intrauterine or postnatal life can also influence the health of their offspring, thus initiating a cycle of disease risk across generations. In this Perspective, we focus on epigenetic mechanisms in germ cells, including DNA methylation, histone modification, and non-coding RNAs, which collectively may provide a non-genetic molecular legacy of prior environmental exposures and influence transcriptional regulation, developmental trajectories, and adult disease risk in offspring...
March 7, 2017: Cell Metabolism
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