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Metabolism and epigenetics

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https://www.readbyqxmd.com/read/29344314/aberrant-expression-and-dna-methylation-of-lipid-metabolism-genes-in-pcos-a-new-insight-into-its-pathogenesis
#1
Jie-Xue Pan, Ya-Jing Tan, Fang-Fang Wang, Ning-Ning Hou, Yu-Qian Xiang, Jun-Yu Zhang, Ye Liu, Fan Qu, Qing Meng, Jian Xu, Jian-Zhong Sheng, He-Feng Huang
Background: Polycystic ovary syndrome (PCOS), whose etiology remains uncertain, is a highly heterogenous and genetically complex endocrine disorder. The aim of this study was to identify differentially expressed genes (DEGs) in granulosa cells (GCs) from PCOS patients and make epigenetic insights into the pathogenesis of PCOS. Results: Included in this study were 110 women with PCOS and 119 women with normal ovulatory cycles undergoing in vitro fertilization acting as the control group...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29341271/review-shows-that-early-fetal-alcohol-exposure-may-cause-adverse-effects-even-when-the-mother-consumes-low-levels
#2
Ihsan Sarman
AIM: Studies are increasingly focusing on the effects of prenatal alcohol exposure (PAE) on child health. The aim of this review was to provide paediatricians with new insights to help them communicate key messages about avoiding alcohol during pregnancy. METHODS: Inspired by the 7th International Conference on Fetal Alcohol Spectrum Disorder, which focused on integrating research, policy and practice, we studied English language papers published since 2010 on how early PAE triggered epigenetic mechanisms that had an impact on the development of some chronic diseases...
January 17, 2018: Acta Paediatrica
https://www.readbyqxmd.com/read/29340017/altered-gnas-imprinting-due-to-folic-acid-deficiency-contributes-to-poor-embryo-development-and-may-lead-to-neural-tube-defects
#3
Li Wang, Shaoyan Chang, Zhen Wang, Shan Wang, Junsheng Huo, Gangqiang Ding, Rui Li, Chi Liu, Shaofang Shangguan, Xiaolin Lu, Ting Zhang, Zhiyong Qiu, Jianxin Wu
Disturbed epigenetic modifications have been linked to the pathogenesis of Neural Tube Defects (NTDs) in those with folate deficiency during pregnancy. However, evidence is lacking to delineate the critical region in epigenome regulated by parental folic acid and mechanisms by which folate deficiency affects normal embryogenesis. Our data from clinical samples revealed the presence of aberrant DNA methylation in GNAS imprinting cluster in NTD samples with low folate concentrations. Results from mouse models indicated that the establishment of GNAS imprinting was influenced by both maternal and paternal folate-deficient diets...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339836/the-role-of-metabolic-enzymes-in-mesenchymal-tumors-and-tumor-syndromes-genetics-pathology-and-molecular-mechanisms
#4
REVIEW
Inga-Marie Schaefer, Jason L Hornick, Judith V M G Bovée
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate...
January 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29339473/identification-of-thioredoxin-interacting-protein-txnip-as-a-downstream-target-for-igf1-action
#5
Karthik Nagaraj, Lena Lapkina-Gendler, Rive Sarfstein, David Gurwitz, Metsada Pasmanik-Chor, Zvi Laron, Shoshana Yakar, Haim Werner
Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339153/inhibition-of-cox-2-and-5-lox-regulates-the-progression-of-colorectal-cancer-by-promoting-pten-and-suppressing-pi3k-akt-pathway
#6
Jian Chang, Nan Tang, Qi Fang, Kongfan Zhu, Lei Liu, Xingcheng Xiong, Zhongchao Zhu, Bixiang Zhang, Mingzhi Zhang, Jing Tao
For colorectal cancer (CRC) patients, local and systemic inflammatory responses have been extensively reported to closely associate with patient survival. However, the specific signalling pathways responsible for carcinogenic responses are unclear. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of PI3K/AKT pathway that is gradually inactivated in cancers through mutation, loss of heterozygosity and others epigenetic mechanisms. In addition, COX and LOX metabolic pathways of arachidonic acid (AA) play a crucial role in promoting adenoma development...
January 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29332359/novel-molecular-and-metabolic-aspects-in-osteosarcoma
#7
Evangelos Tsiambas, Panagiotis P Fotiades, Chrissa Sioka, Dimitrios Kotrotsios, Evangelia Gkika, Andreas Fotopoulos, Stylianos N Mastronikolis, Ilianna E Armata, Evangelos Giotakis, Vasileios Ragos
Osteosarcoma (OS) is the most frequent bone-forming malignancy in children and adolescents. Concerning its molecular landscape, there is no a direct relationship with a specific gene, but a combination of genetic events. A broad spectrum of activated oncogenes and downregulated suppressor genes has been already explored and considered crucial for its progressive pathogenesis. Mechanisms of gene deregulation include amplifications, point mutations, allelic losses and also epigenetic abnormalities such as aberrant promoter methylation...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331887/idh1r132h-promotes-malignant-transformation-of-benign-prostatic-epithelium-by-dysregulating-micrornas-involvement-of-igf1r-akt-stat3-signaling-pathway
#8
Lili Zhang, Mei Qi, Tingting Feng, Jing Hu, Lin Wang, Xinjun Li, Wei Gao, Hui Liu, Meng Jiao, Zhen Wu, Xinnuo Bai, Yifan Bie, Long Liu, Bo Han
Risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer (PCa). Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. Mutant IDH1 has been identified in various human malignancies, and IDH1R132H constituted the vast majority of mutational events of IDH1. Most recent studies suggested that IDH1 mutations define a methylator subtype in PCa...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29330620/impact-of-sirtuin-1-expression-on-h3k56-acetylation-and-oxidative-stress-a-double-blind-randomized-controlled-trial-with-resveratrol-supplementation
#9
Simona Bo, Gabriele Togliatto, Roberto Gambino, Valentina Ponzo, Giusy Lombardo, Rosalba Rosato, Maurizio Cassader, Maria Felice Brizzi
AIMS: Sirtuin-1 (SIRT-1) down-regulation in type 2 diabetes mellitus (T2DM) has been associated with epigenetic markers of oxidative stress. We herein aim to evaluate whether an increase in SIRT-1 expression affects histone 3 acetylation at the 56 lysine residue (H3K56ac) in T2DM patients randomly selected to receive either resveratrol (40 mg or 500 mg) or a placebo for 6 months. The primary outcome is changes in the H3K56ac level by variation in SIRT-1 expression and the secondary outcome is the evidence of association between SIRT-1 level, antioxidant markers (TAS), and metabolic variables...
January 12, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29330325/cutting-edge-plasmodium-falciparum-induces-trained-innate-immunity
#10
Jacob E Schrum, Juliet N Crabtree, Katherine R Dobbs, Michael C Kiritsy, George W Reed, Ricardo T Gazzinelli, Mihai G Netea, James W Kazura, Arlene E Dent, Katherine A Fitzgerald, Douglas T Golenbock
Malarial infection in naive individuals induces a robust innate immune response. In the recently described model of innate immune memory, an initial stimulus primes the innate immune system to either hyperrespond (termed training) or hyporespond (tolerance) to subsequent immune challenge. Previous work in both mice and humans demonstrated that infection with malaria can both serve as a priming stimulus and promote tolerance to subsequent infection. In this study, we demonstrate that initial stimulation with Plasmodium falciparum-infected RBCs or the malaria crystal hemozoin induced human adherent PBMCs to hyperrespond to subsequent ligation of TLR2...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29329322/methylene-tetrahydrofolate-reductase-contributes-to-allergic-airway-disease
#11
Kenneth R Eyring, Brent S Pedersen, Kenneth N Maclean, Sally P Stabler, Ivana V Yang, David A Schwartz
RATIONALE: Environmental exposures strongly influence the development and progression of asthma. We have previously demonstrated that mice exposed to a diet enriched with methyl donors during vulnerable periods of fetal development can enhance the heritable risk of allergic airway disease through epigenetic changes. There is conflicting evidence on the role of folate (one of the primary methyl donors) in modifying allergic airway disease. OBJECTIVES: We hypothesized that blocking folate metabolism through the loss of methylene-tetrahydrofolate reductase (Mthfr) activity would reduce the allergic airway disease phenotype through epigenetic mechanisms...
2018: PloS One
https://www.readbyqxmd.com/read/29328908/metabolic-induction-of-trained-immunity-through-the-mevalonate-pathway
#12
Siroon Bekkering, Rob J W Arts, Boris Novakovic, Ioannis Kourtzelis, Charlotte D C C van der Heijden, Yang Li, Calin D Popa, Rob Ter Horst, Julia van Tuijl, Romana T Netea-Maier, Frank L van de Veerdonk, Triantafyllos Chavakis, Leo A B Joosten, Jos W M van der Meer, Henk Stunnenberg, Niels P Riksen, Mihai G Netea
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328786/connections-between-metabolism-and-epigenetics-in-programming-cellular-differentiation
#13
Danielle A Chisolm, Amy S Weinmann
Researchers are intensifying efforts to understand the mechanisms by which changes in metabolic states influence differentiation programs. An emerging objective is to define how fluctuations in metabolites influence the epigenetic states that contribute to differentiation programs. This is because metabolites such as S-adenosylmethionine, acetyl-CoA, α-ketoglutarate, 2-hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists for the activities of epigenetic-modifying complexes and for epigenetic modifications...
January 12, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29325932/riboflavin-attenuates-myocardial-injury-via-lsd1-mediated-crosstalk-between-phospholipid-metabolism-and-histone-methylation-in-mice-with-experimental-myocardial-infarction
#14
Peng Wang, Fan Fan, Xiao Li, Xiaolei Sun, Leilei Ma, Jian Wu, Cheng Shen, Hong Zhu, Zhen Dong, Cong Wang, Shuqi Zhang, Xiaona Zhao, Xin Ma, Yunzeng Zou, Kai Hu, Aijun Sun, Junbo Ge
The underlying mechanisms responsible for the cardioprotective effects of riboflavin remain elusive. Current study tested the hypothesis that riboflavin protects injured myocardium via epigenetic modification of LSD1. Here we showed that myocardial injury was attenuated and cardiac function was improved in riboflavin-treated mice with experimental myocardial infarction (MI), while these protective effects of riboflavin could be partly blocked by cotreatment with LSD1 inhibitor. Riboflavin also reduced apoptosis in hypoxic (1% oxygen) H9C2 cell lines...
January 8, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29325019/deep-molecular-phenotypes-link-complex-disorders-and-physiological-insult-to-cpg-methylation
#15
Shaza B Zaghlool, Dennis O Mook-Kanamori, Sara Kader, Nisha Stephan, Anna Halama, Rudolf Engelke, Hina Sarwath, Eman K Al-Dous, Yasmin A Mohamoud, Werner Roemisch-Margl, Jerzy Adamski, Gabi Kastenmüller, Nele Friedrich, Alessia Visconti, Pei-Chien Tsai, Tim Spector, Jordana Bell, Mario Falchi, Annika Wahl, Melanie Waldenberger, Annette Peters, Christian Gieger, Maija Pezer, Gordan Lauc, Johannes Graumann, Joel A Malek, Karsten Suhre
Epigenetic regulation of cellular function provides a mechanism for rapid organismal adaptation to changes in health, lifestyle, and environment. Associations of cytosine-guanine di-nucleotide (CpG) methylation with clinical endpoints that overlap with metabolic phenotypes suggest a regulatory role for these CpG sites in the body's response to disease or environmental stress. We previously identified 20 CpG sites in an epigenome-wide association study (EWAS) with metabolomics that were also associated in recent EWASs with diabetes-, obesity-, and smoking-related endpoints...
January 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29322286/hyperglycemia-and-aberrant-o-glcnacylation-contributions-to-tumor-progression
#16
REVIEW
Andréia Vasconcelos-Dos-Santos, Rafaela Muniz de Queiroz, Bruno da Costa Rodrigues, Adriane R Todeschini, Wagner B Dias
A number of cancer types have shown an increased prevalence and a higher mortality rate in patients with hyperglycemic associated pathologies. Although the correlation between diabetes and cancer incidence has been increasingly reported, the underlying molecular mechanisms beyond this association are not yet fully understood. Recent studies have suggested that high glucose levels support tumor progression through multiple mechanisms that are hallmarks of cancer, including cell proliferation, resistance to apoptosis, increased cell migration and invasiveness, epigenetic regulation (hyperglycemic memory), resistance to chemotherapy and altered metabolism...
January 11, 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29321036/maternal-engineered-nanomaterial-inhalation-during-gestation-alters-the-fetal-transcriptome
#17
P A Stapleton, Q A Hathaway, C E Nichols, A B Abukabda, M V Pinti, D L Shepherd, C R McBride, J Yi, V C Castranova, J M Hollander, T R Nurkiewicz
BACKGROUND: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation...
January 10, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29316660/regulation-of-hepatic-ugt2b15-by-methylation-in-adults-of-asian-descent
#18
Steffen G Oeser, Jon-Paul Bingham, Abby C Collier
The hepatic uridine 5'-diphosphate-glucuronosyl transferases (UGTs) are critical for detoxifying endo- and xenobiotics. Since UGTs are also dynamically responsive to endogenous and exogenous stimuli, we examined whether epigenetic DNA methylation can regulate hepatic UGT expression and differential effects of ethnicity, obesity, and sex. The methylation status of UGT isoforms was determined with Illumina Methylation 450 BeadChip arrays, with genotyping confirmed by sequencing and gene expression confirmed with quantitative reverse transcriptase polymerase chain reaction (q-RT-PCR)...
January 7, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29311218/sirt1-a-guardian-of-the-development-of-diabetic-retinopathy
#19
Manish Mishra, Arul J Duraisamy, Renu A Kowluru
Diabetic retinopathy is a multifactorial disease, and the exact mechanism of its pathogenesis remains obscure. A multifunctional deacetylase Sirtuin 1 (Sirt1), is implicated in regulation of many cellular functions and transcription of genes, and retinal Sirt1 is inhibited in diabetes. Our aim is to determine the role of Sirt1 in the development of diabetic retinopathy, and elucidate the molecular mechanism of its downregulation. Using mice overexpressing Sirt1, diabetic for 8 month, structural, functional and metabolic abnormalities were investigated in vascular and neuronal retina...
January 8, 2018: Diabetes
https://www.readbyqxmd.com/read/29310712/genome-wide-screening-of-dna-methylation-in-bovine-blastocysts-with-different-kinetics-of-development
#20
Jessica Ispada, Camila Bruna de Lima, Marc-André Sirard, Patrícia Kubo Fontes, Marcelo Fábio Gouveia Nogueira, Kelly Annes, Marcella Pecora Milazzotto
BACKGROUND: The timing of the first cell divisions may predict the developmental potential of an embryo, including its ability to establish pregnancy. Besides differences related to metabolism, stress, and survival, embryos with different speeds of development present distinct patterns of gene expression, mainly related to energy and lipid metabolism. As gene expression is regulated by epigenetic factors, and that includes DNA methylation patterns, in this study we compared the global DNA methylation profile of embryos with different kinetics of development in order to identify general pathways and regions that are most influenced by this phenotype...
January 8, 2018: Epigenetics & Chromatin
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