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https://www.readbyqxmd.com/read/28700951/diabetic-retinopathy-metabolic-memory-and-epigenetic-modifications
#1
Renu A Kowluru
Retinopathy, a sight-threatening disease, remains one of the most feared complications of diabetes. Although hyperglycemia is the main initiator progression of diabetic retinopathy continues even after re-institution of normal glycemic control in diabetic patients, and the deleterious effects of prior hyperglycemic insult depend on the duration and the severity of this insult, suggesting a 'metabolic memory' phenomenon. Metabolic memory phenomenon is successfully duplicated in the experimental models of diabetic retinopathy...
July 9, 2017: Vision Research
https://www.readbyqxmd.com/read/28698407/ccctc-binding-factor-inhibits-breast-cancer-cell-proliferation-and-metastasis-via-inactivation-of-the-nuclear-factor-kappab-pathway
#2
Jie Wu, Peng-Chang Li, Jun-Yi Pang, Guo-You Liu, Xue-Min Xie, Jia-Yao Li, Yi-Cong Yin, Jian-Hua Han, Xiu-Zhi Guo, Ling Qiu
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28693405/genetics-and-immunodysfunction-underlying-beh%C3%A3-et-s-disease-and-immunomodulant-treatment-approaches
#3
Arash Salmaninejad, Arezoo Gowhari, Seyedmojtaba Hosseini, Saeed Aslani, Meysam Yousefi, Tayyeb Bahrami, Masoume Ebrahimi, Abolfazl Nesaei, Masoud Zal
Behçet's disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28679862/mysm1-2a-dub-is-an-epigenetic-regulator-in-human-melanoma-and-contributes-to-tumor-cell-growth
#4
Christina Wilms, Carsten M Kroeger, Adelheid V Hainzl, Ishani Banik, Clara Bruno, Ioanna Krikki, Vida Farsam, Meinhard Wlaschek, Martina V Gatzka
Histone modifying enzymes, such as histone deacetylases (HDACs) and polycomb repressive complex (PRC) components, have been implicated in regulating tumor growth, epithelial-mesenchymal transition, tumor stem cell maintenance, or repression of tumor suppressor genes - and may be promising targets for combination therapies of melanoma and other cancers. According to recent findings, the histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53-axis in hematopoiesis and tissue differentiation in mice, in part by modulating DNA-damage responses in stem cell and progenitor compartments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28679371/cpg-promoter-methylation-of-the-alkbh3-alkylation-repair-gene-in-breast-cancer
#5
Olafur Andri Stefansson, Stefan Hermanowicz, Jasper van der Horst, Holmfridur Hilmarsdottir, Zuzanna Staszczak, Jon Gunnlaugur Jonasson, Laufey Tryggvadottir, Thorkell Gudjonsson, Stefan Sigurdsson
BACKGROUND: DNA repair of alkylation damage is defective in various cancers. This occurs through somatically acquired inactivation of the MGMT gene in various cancer types, including breast cancers. In addition to MGMT, the two E. coli AlkB homologs ALKBH2 and ALKBH3 have also been linked to direct reversal of alkylation damage. However, it is currently unknown whether ALKBH2 or ALKBH3 are found inactivated in cancer. METHODS: Methylome datasets (GSE52865, GSE20713, GSE69914), available through Omnibus, were used to determine whether ALKBH2 or ALKBH3 are found inactivated by CpG promoter methylation...
July 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28677663/inter-strain-differences-in-line-1-dna-methylation-in-the-mouse-hematopoietic-system-in-response-to-exposure-to-ionizing-radiation
#6
Isabelle R Miousse, Jianhui Chang, Lijian Shao, Rupak Pathak, Étienne Nzabarushimana, Kristy R Kutanzi, Reid D Landes, Alan J Tackett, Martin Hauer-Jensen, Daohong Zhou, Igor Koturbash
Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons are the major repetitive elements in mammalian genomes. LINE-1s are well-accepted as driving forces of evolution and critical regulators of the expression of genetic information. Alterations in LINE-1 DNA methylation may lead to its aberrant activity and are reported in virtually all human cancers and in experimental carcinogenesis. In this study, we investigated the endogenous DNA methylation status of the 5' untranslated region (UTR) of LINE-1 elements in the bone marrow hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs), and mononuclear cells (MNCs) in radioresistant C57BL/6J and radiosensitive CBA/J mice and in response to ionizing radiation (IR)...
July 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28675037/sensitive-detection-of-dna-lesions-by-bulge-enhanced-highly-specific-coamplification-at-lower-denaturation-temperature-polymerase-chain-reaction
#7
Yu Feng, Shuang Cai, Guoliang Xiong, Guanfei Zhang, Shihui Wang, Xin Su, Changyuan Yu
Mutagenic modifications of nucleotides or DNA lesions that result from environmental stress have proven to be associated with a variety of diseases, particularly cancer. The method for accurately detecting the lesions is therefore of great importance for biomedical research and toxicity study. We develop a sensitive and low-cost bulge-enhanced coamplification at lower denaturation temperature polymerase chain reaction (COLD-PCR) method for detecting DNA lesions (uracil and 8-oxoguanine) by combining an in vitro base excision repair (BER) pathway and COLD-PCR...
July 12, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28670762/tribbles-2-mediates-cisplatin-sensitivity-and-dna-damage-response-in-epithelial-ovarian-cancer
#8
Daniel Kritsch, Franziska Hoffmann, Daniel Steinbach, Lars Jansen, Stella Mary Photini, Mieczyslaw Gajda, Alexander S Mosig, Jürgen Sonnemann, Sven Peters, Margarita Melnikova, Jürgen Thomale, Matthias Dürst, Ingo B Runnebaum, Norman Häfner
Aim was to identify methylated genes with functional involvement in cisplatin-resistance development of epithelial ovarian cancer (EOC). Genome-wide analyses of hypermethylated CpG-islands in resistant cell lines in combination with qRT-PCR analyses were used to identify epigenetically silenced genes. EOC-type-II tumors were analyzed for gene methylation and expression and TCGA data were interrogated in-silico. Experiments revealed 37 commonly hypermethylated genes in resistant cells of which Tribbles 2 (TRIB2) showed the most pronounced down-regulation on mRNA level and was characterized further...
July 3, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28666128/terra-rna-antagonizes-atrx-and-protects-telomeres
#9
Hsueh-Ping Chu, Catherine Cifuentes-Rojas, Barry Kesner, Eric Aeby, Hun-Goo Lee, Chunyao Wei, Hyun Jung Oh, Myriam Boukhali, Wilhelm Haas, Jeannie T Lee
Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28657421/chemo-brain-from-discerning-mechanisms-to-lifting-the-brain-fog-an-aging-connection
#10
Anna Kovalchuk, Bryan Kolb
Mounting evidence indicates that cancer treatments cause numerous deleterious effects, including central nervous system (CNS) toxicity. Chemotherapy-caused CNS side effects encompass changes in cognitive function, memory, and attention, to name a few. Although chemotherapy treatment-induced side effects occur in 16-75% of all patients, the mechanisms of these effects are not well understood. We have recently proposed a new epigenetic theory of chemo brain and, in a pioneer study, determined that cytotoxic chemotherapy agents induce oxidative DNA damage and affect molecular and epigenetic processes in the brain, and may be associated with brain aging processes...
June 28, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28649883/middle-down-proteomics-a-still-unexploited-resource-for-chromatin-biology
#11
Simone Sidoli, Benjamin A Garcia
Analysis of histone post-translational modifications (PTMs) by mass spectrometry (MS) has become a fundamental tool for the characterization of chromatin composition and dynamics. Histone PTMs benchmark several biological states of chromatin, including regions of active enhancers, active/repressed gene promoters and damaged DNA. These complex regulatory mechanisms are often defined by combinatorial histone PTMs; for instance, active enhancers are commonly occupied by both marks H3K4me1 and H3K27ac. The traditional bottom-up MS strategy identifies and quantifies short (aa 4-20) tryptic peptides, and it is thus not suitable for the characterization of combinatorial PTMs...
June 28, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28642588/epigenetic-targeting-drugs-potentiate-chemotherapeutic-effects-in-solid-tumor-therapy
#12
Jingjing Li, Dapeng Hao, Li Wang, Haitao Wang, Yuan Wang, Zhiqiang Zhao, Peipei Li, Chuxia Deng, Li-Jun Di
Epigenetic therapy is a novel tumor therapeutic method and refers to the targeting of the aberrant epigenetic modifications presumably at cancer-related genes by chemicals which are epigenetic targeting drugs (ETDs). Not like in treating hematopoietic cancer, the clinical trials investigating the potential use of ETDs in the solid tumor is not encouraging. Instead, the curative effects of ETD delivered together with DNA targeting chemo drugs (DTDs) are quite promising according to our meta-analysis. To investigate the synergistic mechanism of ETD and DTD drug combination, the therapeutic effect was studied using both cell lines and mouse engrafted tumors...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641532/trimethylamine-n-oxide-tmao-as-a-new-potential-therapeutic-target-for-insulin-resistance-and-cancer
#13
Jens Oellgaard, Signe Abitz Winther, Tobias Schmidt Hansen, Peter Rossing, Bernt Johan von Scholten
BACKGROUND: The intake of animal products in food has been associated with both the development of insulin resistance and gastrointestinal cancers (GIC). Through the digestion of animal protein and other constituents of animal products, the commensal bacteria in the gut (the gut microbiota) forms metabolites that can contribute to the development of both insulin resistance and cancer. Trimethylamine-N-Oxide (TMAO) is such a molecule and has recently drawn a lot of attention as it may be a risk factor for - and a link between - the gut microbiota and cardiovascular and renal disease...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28639476/effects-of-folic-acid-on-dnmt1-gap43-and-vegfr1-in-intrauterine-growth-restriction-filial-rats
#14
Ying-Xue Ding, Hong Cui
OBJECTIVE: To investigate the effect of a folic acid intervention on the outcome of intrauterine growth restriction (IUGR) filial rats and changes in DNA methyltransferase 1 (DNMT1), growth-associated protein 43 (GAP43), and vascular endothelial growth factor receptor 1 (VEGFR1). METHODS: The IUGR animal model was established using a starvation method in pregnant rats. The animals were randomly divided into 4 groups: normal controls, IUGR rats, IUGR rats given folic acid, and IUGR rats given normal saline...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28634176/impact-of-glycemic-variability-on-chromatin-remodeling-oxidative-stress-and-endothelial-dysfunction-in-type-2-diabetic-patients-with-target-hba1c-levels
#15
Sarah Costantino, Francesco Paneni, Rodolfo Battista, Lorenzo Castello, Giuliana Capretti, Sergio Chiandotto, Luigi Tanese, Giulio Russo, Dario Pitocco, Gaetano A Lanza, Massimo Volpe, Thomas F Lüscher, Francesco Cosentino
Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D), however the underlining mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigates whether epigenetic regulation of the adaptor protein p66(Shc), a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in T2D patients despite IGC...
June 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28631441/genetic-landscape-and-deregulated-pathways-in-b-cell-lymphoid-malignancies
#16
R Rosenquist, S Beà, M-Q Du, B Nadel, Q Pan-Hammarström
With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma...
June 20, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28629775/8-oxo-7-8-dihydroguanine-friend-and-foe-epigenetic-like-regulator-versus-initiator-of-mutagenesis
#17
REVIEW
Aaron M Fleming, Cynthia J Burrows
A high flux of reactive oxygen species during oxidative stress results in oxidative modification of cellular components including DNA. Oxidative DNA "damage" to the heterocyclic bases is considered deleterious because polymerases may incorrectly read the modifications causing mutations. A prominent member in this class is the oxidized guanine base 8-oxo-7,8-dihydroguanine (OG) that is moderately mutagenic effecting G→T transversion mutations. Recent reports have identified that formation of OG in G-rich regulatory elements in the promoters of the VEGF, TNFα, and SIRT1 genes can increase transcription via activation of the base excision repair (BER) pathway...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28613268/vitamin-e-modifies-high-fat-diet-induced-increase-of-dna-strand-breaks-and-changes-in-expression-and-dna-methylation-of-dnmt1-and-mlh1-in-c57bl-6j-male-mice
#18
Marlene Remely, Franziska Ferk, Sonja Sterneder, Tahereh Setayesh, Tatjana Kepcija, Sylvia Roth, Rahil Noorizadeh, Martina Greunz, Irene Rebhan, Karl-Heinz Wagner, Siegfried Knasmüller, Alexander Haslberger
Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD) or a control diet (CD) with and without vitamin E supplementation (4.5 mg/kg body weight (b.w.)) for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene (MLH1) were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1...
June 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28600325/hira-deficiency-in-muscle-fibers-causes-hypertrophy-and-susceptibility-to-oxidative-stress
#19
Nicolas Valenzuela, Benjamin Soibam, Lerong Li, Jing Wang, Lauren A Byers, Yu Liu, Robert J Schwartz, M David Stewart
Nucleosome assembly proceeds through DNA replication-coupled or replication-independent mechanisms. For skeletal myocytes, whose nuclei have permanently exited the cell cycle, replication-independent assembly is the only mode available for chromatin remodeling. For this reason, any nucleosome composition alterations accompanying transcriptional responses to physiological signals must occur through a DNA replication-independent pathway. HIRA is the histone chaperone primarily responsible for replication-independent incorporation of histone variant H3...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28582660/the-phytochemical-3-3-diindolylmethane-decreases-expression-of-ar-controlled-dna-damage-repair-genes-through-repressive-chromatin-modifications-and-is-associated-with-dna-damage-in-prostate-cancer-cells
#20
Zoraya Palomera-Sanchez, Gregory W Watson, Carmen P Wong, Laura M Beaver, David E Williams, Roderick H Dashwood, Emily Ho
Androgen receptor (AR) is a transcription factor involved in normal prostate physiology and prostate cancer (PCa) development. 3,3'-Diindolylmethane (DIM) is a promising phytochemical agent against PCa that affects AR activity and epigenetic regulators in PCa cells. However, whether DIM suppresses PCa via epigenetic regulation of AR target genes is unknown. We assessed epigenetic regulation of AR target genes in LNCaP PCa cells and showed that DIM treatment led to epigenetic suppression of AR target genes involved in DNA repair (PARP1, MRE11, DNA-PK)...
May 25, 2017: Journal of Nutritional Biochemistry
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