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https://www.readbyqxmd.com/read/29329106/genetic-mutations-associated-with-neonatal-diabetes-mellitus-in-omani-patients
#1
Aisha Al Senani, Nishath Hamza, Hanan Al Azkawi, Manal Al Kharusi, Nashat Al Sukaiti, Maryam Al Badi, Moza Al Yahyai, Matthew Johnson, Elisa De Franco, Sarah Flanagan, Andrew Hattersley, Sian Ellard, Waad-Allah Mula-Abed
BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare disorder worldwide where diabetes is diagnosed in the first 6 months of life. However, Oman has a relatively high incidence of NDM. METHODS: In this study, we investigated the genetic etiologies underlying NDM and their prevalence in Oman. We collected a cohort of 24 NDM patients, with and without genetic diagnosis, referred to our center from 2007 to 2015. All patients without a genetic diagnosis were tested for mutations in 23 NDM-associated genes using a custom-targeted next-generation sequencing (NGS) panel and methylation analysis of the 6q24 locus...
January 12, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29326313/dna-methylation-and-age-independent-cardiovascular-risk-an-epigenome-wide-approach-the-regicor-registre-giron%C3%A3-del-cor-study
#2
Alba Fernández-Sanlés, Sergi Sayols-Baixeras, Santiago Curcio, Isaac Subirana, Jaume Marrugat, Roberto Elosua
OBJECTIVE: The objectives of this study were to decipher whether age-independent cardiovascular risk is associated with DNA methylation at 5'-cytosine-phosphate-guanine-3' (CpG) level and to determine whether these differential methylation signatures are associated with the incidence of cardiovascular events. APPROACH AND RESULTS: We designed a 2-stage, cross-sectional, epigenome-wide association study. Age-independent cardiovascular risk calculation was based on vascular age and on the residuals of the relationship between age and cardiovascular risk...
January 11, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29325019/deep-molecular-phenotypes-link-complex-disorders-and-physiological-insult-to-cpg-methylation
#3
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/29321829/dna-methylation-in-stroke-update-of-latest-advances
#4
REVIEW
Jerzy Krupinski, Caty Carrera, Elena Muiño, Nuria Torres, Raid Al-Baradie, Natalia Cullell, Israel Fernandez-Cadenas
Epigenetic modifications are hereditable and modifiable factors that do not alter the DNA sequence. These epigenetic factors include DNA methylation, acetylation of histones and non-coding RNAs. Epigenetic factors have mainly been associated with cancer but also with other diseases and conditions such as diabetes or obesity. In addition, epigenetic modifications could play an important role in cardiovascular diseases, including stroke. We review the latest advances in stroke epigenetics, focusing on DNA methylation studies and the future perspectives in this field...
2018: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/29320705/an-adipose-tissue-atlas-an-image-guided-identification-of-human-like-bat-and-beige-depots-in-rodents
#5
Fang Zhang, Guiyang Hao, Mengle Shao, Kien Nham, Yu An, Qiong Wang, Yi Zhu, Christine M Kusminski, Gedaa Hassan, Rana K Gupta, Qiwei Zhai, Xiankai Sun, Philipp E Scherer, Orhan K Oz
[18F]Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) imaging has been invaluable for visualizing metabolically active adipose tissues in humans with potential anti-diabetic and anti-obesity effects. To explore whether mice display human-like fat depots in anatomically comparable regions, we mapped fat depots using glucose or fatty acid imaging tracers, such as 18F-FDG through PET/CT or [123/125I]-β-methyl-p-iodophenyl-pentadecanoic acid with SPECT/CT imaging, to analogous depots in mice. Using this type of image analysis with both probes, we define a large number of additional areas of high metabolic activity corresponding to novel fat pads...
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29314572/high-fat-diet-induced-tcf7l2-promoter-methylation-impairs-%C3%AE-cell-function-in-mouse-pancreatic-islets
#6
Yun Hu, Ping Shi, Ke He, Yun-Qing Zhu, Fan Yang, Min Yang, Bang-Shun He, Xiao-Ming Mao
BACKGROUND: The TCF7L2 (transcription factor 7 like 2) gene is strongly associated with type 2 diabetes (T2D) risk. However, many people without the TCF7L2 at-risk allele develop T2D. The aim of this study was to investigate altered Tcf7l2 DNA methylation and gene expression caused by high-fat diets (HFDs). METHODS: C57BL/6 mice were fed either a HFD or normal diet for 8 weeks and intraperitoneal glucose tolerance tests were performed. Pancreatic islets were sorted for bisulfite sequencing PCR to determine DNA methylation status...
January 4, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29312822/effect-of-dark-sweet-cherry-powder-consumption-on-the-gut-microbiota-short-chain-fatty-acids-and-biomarkers-of-gut-health-in-obese-db-db-mice
#7
Jose F Garcia-Mazcorro, Nara N Lage, Susanne Mertens-Talcott, Stephen Talcott, Boon Chew, Scot E Dowd, Jorge R Kawas, Giuliana D Noratto
Cherries are fruits containing fiber and bioactive compounds (e.g., polyphenolics) with the potential of helping patients with diabetes and weight disorders, a phenomenon likely related to changes in the complex host-microbiota milieu. The objective of this study was to investigate the effect of cherry supplementation on the gut bacterial composition, concentrations of caecal short-chain fatty acids (SCFAs) and biomarkers of gut health using an in vivo model of obesity. Obese diabetic (db/db) mice received a supplemented diet with 10% cherry powder (supplemented mice, n = 12) for 12 weeks; obese (n = 10) and lean (n = 10) mice served as controls and received a standard diet without cherry...
2018: PeerJ
https://www.readbyqxmd.com/read/29304076/serine-racemase-deletion-attenuates-neurodegeneration-and-microvascular-damage-in-diabetic-retinopathy
#8
Hironori Ozaki, Ran Inoue, Takako Matsushima, Masakiyo Sasahara, Atsushi Hayashi, Hisashi Mori
Diabetic retinopathy (DR) is a leading cause of blindness. DR is recognized as a microvascular disease and inner retinal neurodegeneration. In the course of retinal neurodegeneration, N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity is involved. Full activation of NMDAR requires binding of agonist glutamate and coagonist glycine or D-serine. D-Serine is produced from L-serine by serine racemase (SRR) and contributes to retinal neurodegeneration in rodent models of DR. However, the involvement of SRR in both neurodegeneration and microvascular damage in DR remains unclear...
2018: PloS One
https://www.readbyqxmd.com/read/29301528/asymmetric-dimethylarginine-adma-symmetric-dimethylarginine-sdma-and-homoarginine-harg-the-adma-sdma-and-harg-paradoxes
#9
EDITORIAL
Dimitrios Tsikas, Alexander Bollenbach, Erik Hanff, Arslan Arinc Kayacelebi
NG-Methylation of L-arginine (Arg) residues in certain proteins by protein arginine methyltransferases and subsequent proteolysis yields NG-monomethyl-L-arginine (MMA), NG,NG-dimethyl-L-arginine (asymmetric dimethylarginine, ADMA) and NG,N'G-dimethyl-L-arginine (symmetric dimethylarginine, SDMA). Biological MMA, ADMA and SDMA occur as free acids in the nM-range and as residues of proteins of largely unknown quantity. Arginine:glycine amidinotransferase (AGAT) catalyzes the synthesis of L-homoarginine (hArg) from free Arg and L-lysine...
January 4, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29295516/impact-of-consuming-extra-virgin-olive-oil-or-nuts-within-a-mediterranean-diet-on-dna-methylation-in-peripheral-white-blood-cells-within-the-predimed-navarra-randomized-controlled-trial-a-role-for-dietary-lipids
#10
Ana Arpón, Fermín I Milagro, Cristina Razquin, Dolores Corella, Ramón Estruch, Montserrat Fitó, Amelia Marti, Miguel A Martínez-González, Emilio Ros, Jordi Salas-Salvadó, José-Ignacio Riezu-Boj, J Alfredo Martínez
DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group...
December 23, 2017: Nutrients
https://www.readbyqxmd.com/read/29289892/discovery-of-novel-high-potent-and-cellular-active-adc-type-ptp1b-inhibitors-with-selectivity-over-tc-ptp-via-modification-interacting-with-c-site
#11
Yongli Du, Yanhui Zhang, Hao Ling, Qunyi Li, Jingkang Shen
PTP1B serving as a key negative regulator of insulin signaling is a novel target for type 2 diabetes and obesity. Modification at ring B of N-{4-[(3-Phenyl-ureido)-methyl]-phenyl}-methane-sulfonamide template to interact with residues Arg47 and Lys41 in the C site of PTP1B by molecular docking aided design resulted in the discovery of a series of novel high potent and selective inhibitors of PTP1B. The structure activity relationship interacting with the C site of PTP1B was well illustrated. Compounds 8 and 18 were shown to be the high potent and most promising PTP1B inhibitors with cellular activity and great selectivity over the highly homologous TCPTP and other PTPs...
December 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29278276/pathological-lesions-and-global-dna-methylation-in-rat-prostate-under-streptozotocin-induced-diabetes-and-melatonin-supplementation
#12
Marina Guimarães Gobbo, Guilherme Henrique Tamarindo, Daniele Lisboa Ribeiro, Silvana Gisele Pegorin de Campos, Sebastião Roberto Taboga, Rejane Maira Góes
Chronic hyperglycemia increases production of reactive oxygen species, which favors carcinogenesis. The association between diabetes and prostate cancer is controversial. Melatonin has antioxidant, anti-inflammatory and antiproliferative properties. We investigated whether low doses of melatonin prevent the tissue alterations caused by diabetes and alter prostate histology of healthy rats. We also investigated whether experimental diabetes promoted the development of pathological lesions in the ventral prostate of rats...
December 26, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29274332/abnormal-cannabidiol-confers-cardioprotection-in-diabetic-rats-independent-of-glycemic-control
#13
Asmaa I Matouk, Ashraf Taye, Mohamed A El-Moselhy, Gehan H Heeba, Abdel A Abdel-Rahman
Chronic GPR18 activation by its agonist abnormal cannabidiol (trans-4-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol; abn-cbd) improves myocardial redox status and function in healthy rats. Here, we investigated the ability of abn-cbd to alleviate diabetes-evoked cardiovascular pathology and the contribution of GPR18 to this effect. Four weeks after diabetes induction by streptozotocin (STZ, 55mg/kg; i.p), male Wistar rats received abn-cbd, the GPR18 antagonist (1,3-dimethoxy-5-methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-,cyclohexen-1-yl]benzene;O-1918), their combination (100µg/kg/day, i...
December 20, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29273724/worsened-outcome-in-patients-with-pancreatic-ductal-carcinoma-on-long-term-diabetes-association-with-e-cadherin1-cdh1-promoter-methylation
#14
Takeshi Saito, Hiroki Mizukami, Satoko Umetsu, Chiaki Uchida, Wataru Inaba, Makoto Abe, Kazuhisa Takahashi, Kazuhiro Kudo, Chieko Itabashi, Soroku Yagihashi, Kenichi Hakamada
Prevalence of pancreatic ductal carcinoma (PDC) is nearly twice in patients with diabetes mellitus, but the reason for this close association remains obscure. Recently promoter methylation of E-cadherin1 (CDH1) and CDKN2A genes, encoding E-cadherin and P16 respectively, are invoked in development of PDC. It is still unclear whether diabetes affects such epigenetic changes and malignant behavior in PDC. In this study, we studied whether diabetes influences the clinico-pathological profile and methylation status of CDH1 and CDKN2A genes in patients with PDC...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29261844/crosstalk-between-histone-and-dna-methylation-in-regulation-of-retinal-matrix-metalloproteinase-9-in-diabetes
#15
Arul J Duraisamy, Manish Mishra, Renu A Kowluru
Purpose: Diabetes activates matrix metalloproteinase-9 (MMP-9), and MMP-9 via damaging retinal mitochondria, activates capillary cell apoptosis. MMP-9 promoter has binding sites for many transcription factors, and in diabetes its promoter undergoes epigenetic modifications, including histone modifications and DNA methylation. Enhancer of Zeste homolog 2 (Ezh2), which catalyzes dimethylation/trimethylation of histone 3 lysine 27 (H3K27me2 and me3), is also associated with DNA methylation...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29244109/gadd45a-promotes-active-dna-demethylation-of-the-mmp-9-promoter-via-base-excision-repair-pathway-in-ages-treated-keratinocytes-and-in-diabetic-male-rat-skin
#16
Liyan Zhou, Wei Wang, Chuan Yang, Tingting Zeng, Mengdie Hu, Xiaoyi Wang, Na Li, Kan Sun, Chuan Wang, Jing Zhou, Meng Ren, Li Yan
Diabetes elevates matrix metalloproteinase-9 (MMP-9) levels in the skin and its keratinocytes, and activated MMP-9 impairs skin wound healing. Epigenetic regulation of the DNA methylation status within the MMP-9 promoter plays an important role in the alteration of MMP-9 expression. Our aim was to investigate the role and mechanism of growth arrest and DNA damage-inducible 45a (GADD45a), a well-known DNA demethylation regulatory protein that mediates DNA methylation, in the regulation of MMP-9 expression. In this study, we showed that GADD45a was markedly upregulated in skin tissues from patients with diabetic foot ulcers, in diabetic rats and in human keratinocyte (HaCaT) cells exposed to advanced glycation end products (AGEs)...
December 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29233026/evaluation-of-4-methyl-2-2-methylbenzyl-amino-1-3-thiazole-5-carboxylic-acid-against-hyperglycemia-insulin-sensitivity-and-oxidative-stress-induced-inflammatory-responses-and-%C3%AE-cell-damage-in-the-pancreas-of-streptozotocin-induced-diabetic-rats
#17
Y N Paudel, M R Ali, S Bawa, S Shah, M Adil, A Siddiqui, A S Basheer, M Q Hassan, M Sharma
4-Methyl-2-[(2-methylbenzyl) amino]-1,3-thiazole-5-carboxylic acid (bioactive compound (BAC)), a novel thiazole derivative, is a xanthine oxidase inhibitor and free radical scavenging agent. Effects of BAC on hyperglycemia, insulin sensitivity, oxidative stress, and inflammatory mediators were evaluated in streptozotocin (STZ)-induced neonatal models of non-insulin-dependent diabetes mellitus (NIDDM) rats where NIDDM was induced in neonatal pups with single intraperitoneal injection of STZ (100 mg/kg). The effect of BAC (10 and 20 mg/kg, p...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29231988/methylation-based-estimated-biological-age-and-cardiovascular-disease
#18
Lars Lind, Erik Ingelsson, Johan Sundström, Agneta Siegbahn, Erik Lampa
BACKGROUND: DNA methylation changes over life at specific sites in the genome, which can be used to estimate "biological age". The aim of this population-based longitudinal cohort study was to investigate the association between estimated biological age and incident cardiovascular disease (CVD). MATERIALS AND METHODS: Based on formulas published by Hannum et al and Horvath et al, "biological age" was calculated using data from the Illumina 450k Bead Methylation chip in 832 participants free from cardiovascular disease in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination)...
December 12, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29228058/altered-intragenic-dna-methylation-of-hook2-gene-in-adipose-tissue-from-individuals-with-obesity-and-type-2-diabetes
#19
Sandra Rodríguez-Rodero, Edelmiro Menéndez-Torre, Gustavo Fernández-Bayón, Paula Morales-Sánchez, Lourdes Sanz, Estrella Turienzo, Juan José González, Ceferino Martinez-Faedo, Lorena Suarez-Gutiérrez, Jessica Ares, Lucia Díaz-Naya, Alicia Martin-Nieto, Juan L Fernández-Morera, Mario F Fraga, Elías Delgado-Álvarez
AIMS/HYPOTHESIS: Failure in glucose response to insulin is a common pathology associated with obesity. In this study, we analyzed the genome wide DNA methylation profile of visceral adipose tissue (VAT) samples in a population of individuals with obesity and assessed whether differential methylation profiles are associated with the presence of type 2 diabetes (T2D). METHODS: More than 485,000 CpG genome sites from VAT samples from women with obesity undergoing gastric bypass (n = 18), and classified as suffering from type 2 diabetes (T2D) or not (no type 2 diabetes, NT2D), were analyzed using DNA methylation arrays...
2017: PloS One
https://www.readbyqxmd.com/read/29227285/shifts-in-podocyte-histone-h3k27me3-regulate-mouse-and-human-glomerular-disease
#20
Syamantak Majumder, Karina Thieme, Sri N Batchu, Tamadher A Alghamdi, Bridgit B Bowskill, M Golam Kabir, Youan Liu, Suzanne L Advani, Kathryn E White, Laurette Geldenhuys, Karthik K Tennankore, Penelope Poyah, Ferhan S Siddiqi, Andrew Advani
Histone protein modifications control fate determination during normal development and dedifferentiation during disease. Here, we set out to determine the extent to which dynamic changes to histones affect the differentiated phenotype of ordinarily quiescent adult glomerular podocytes. To do this, we examined the consequences of shifting the balance of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark in podocytes. Adriamycin nephrotoxicity and subtotal nephrectomy (SNx) studies indicated that deletion of the histone methylating enzyme EZH2 from podocytes decreased H3K27me3 levels and sensitized mice to glomerular disease...
December 11, 2017: Journal of Clinical Investigation
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