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Demethylation

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https://www.readbyqxmd.com/read/28733611/integrin-%C3%AE-6%C3%AE-4-upregulates-amphiregulin-and-epiregulin-through-base-excision-repair-mediated-dna-demethylation-and-promotes-genome-wide-dna-hypomethylation
#1
Brittany L Carpenter, Jinpeng Liu, Lei Qi, Chi Wang, Kathleen L O'Connor
Aberrant DNA methylation patterns are a common theme across all cancer types. Specific DNA demethylation of regulatory sequences can result in upregulation of genes that are critical for tumor development and progression. Integrin α6β4 is highly expressed in pancreatic carcinoma and contributes to cancer progression, in part, through the specific DNA demethylation and upregulation of epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG). Whole genome bisulfite sequencing (WGBS) revealed that integrin α6β4 signaling promotes an overall hypomethylated state and site specific DNA demethylation of enhancer elements within the proximal promoters of AREG and EREG...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733028/bifidobacterium-longum-affects-the-methylation-level-of-forkhead-box-p3-promoter-in-2-4-6-trinitrobenzenesulphonic-acid-induced-colitis-in-rats
#2
Ming Zhang, Lixing Zhou, Shu Zhang, Yang Yang, Lei Xu, Zichun Hua, Xiaoping Zou
Bifidobacterium longum (B. Longum) is a common probiotic colonized in the human gut and against the development of chronic inflammation including inflammatory bowel disease (IBD). But the underlying mechanism remains unknown. The aim of this study was to evaluate the affection of B. longum on the methylation levels of forkhead box P3 (Foxp3) promoter. 2, 4, 6-trinitrobenzenesulphonic acid (TNBS)-induced colitis rat models were treated with B. longum or medium, respectively. The genomic DNA of spleen peripheral blood mononuclear cells (PBMC) cells was extracted...
July 18, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28732347/histone-demethylase-jmjd2c-epigenetic-regulators-in-tumors
#3
REVIEW
Chengcheng Zhang, Zhongqi Wang, Qing Ji, Qi Li
Histone methylation is one of the major epigenetic modifications, and various histone methylases and demethylases participate in the epigenetic regulating. JMJD2C has been recently identified as one of the histone lysine demethylases. As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731456/upregulation-of-tet-activity-with-ascorbic-acid-induces-epigenetic-modulation-of-lymphoma-cells
#4
N Shenoy, T Bhagat, E Nieves, M Stenson, J Lawson, G S Choudhary, T Habermann, G Nowakowski, R Singh, X Wu, A Verma, T E Witzig
The Ten Eleven Translocation (TET) enzymes have been found to be mutated in both diffuse large B-cell (DLBCL) and peripheral T-cell (PTCL) lymphomas resulting in DNA hypermethylation. Recent studies in embryonal stem cells showed that ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity. We hypothesized that AA could potentially enhance TET activity in lymphoma cells to cause DNA demethylation, reactivate expression of tumor suppressor genes and enhance chemosensitivity...
July 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28724364/tamoxifen-reverses-epithelial-mesenchymal-transition-by-demethylating-mir-200c-in-triple-negative-breast-cancer-cells
#5
Qian Wang, Yu Cheng, Yan Wang, Yibo Fan, Ce Li, Ye Zhang, Yiding Wang, Qian Dong, Yanju Ma, Yue-E Teng, Xiujuan Qu, Yunpeng Liu
BACKGROUND: Although the efficacy of tamoxifen (TAM) for breast cancer has been attributed to inducing cell cycle arrest and apoptosis by inhibiting estrogen receptor (ER) signaling, recent evidence indicates that TAM also possesses ER-independent antitumor activity through an unclear mechanism. The present study investigated the anti-tumor mechanism of TAM on mesenchymal triple-negative breast cancer (TNBC). METHODS: The inhibitory effect of TAM on tumor migration and metastasis was analyzed by transwell chamber in vitro and by murine xenograft model in vivo...
July 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#6
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721828/mir-149-as-a-potential-molecular-target-for-cancer
#7
Suet Hui Ow, Pei Jou Chua, Boon Huat Bay
MicroRNAs (miRNAs) are small, non-coding nucleotides that regulate the expression of proteins. They play major roles in fundamental cellular processes. Aberrant expression of miRNAs has been frequently detected in cancers. miR-149 has been implicated in tumor progression by regulating cellular proliferation, migration, invasion, epithelial-mesenchymal-transition and chemoresistance. There have been reports that miR-149 can function both as an oncogene or tumor suppressor, depending on the type of cancer, thereby giving rise to the possibility of utilizing miR-149 mimics and inhibitors for cancer therapy...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28720493/crystal-structures-of-monkey-and-mouse-nicotinamide-n-methyltransferase-nnmt-bound-with-end-product-1-methyl-nicotinamide
#8
Srinivasan Swaminathan, Swarnakumari Birudukota, Manish Kumar Thakur, Reejuana Parveen, Saravanan Kandan, Suresh Juluri, Shama Shaik, Niranjan Naranapura Anand, Raghunadha Reddy Burri, Rajendra Kristam, Sridharan Rajagopal, Herman Schreuder, Thomas Langer, Christine Rudolph, Sven Ruf, Saravanakumar Dhakshinamoorthy, Ramachandraiah Gosu, Aimo Kannt
Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl-L-methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 Å and 1.88 Å respectively. The structural fold of these enzymes is identical to human NNMT...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28719139/identification-of-metabolites-in-human-and-rat-urine-after-oral-administration-of-xiao-qing-long-tang-granule-using-ultra-high-performance-liquid-chromatography-combined-with-quadrupole-time-of-flight-mass-spectrometry
#9
Lei Zhou, Qiang Zhang, Wen Qi, Shuai Yan, Jialin Qu, Toshiaki Makino, Dan Yuan
Xiao-Qing-Long-Tang is a traditional Chinese formula used for the treatment of cold syndrome, bronchitis, and nasal allergies for thousands of years. However, the in vivo integrated metabolism of its multiple components and the active chemical constituents of Xiao-Qing-Long-Tang remain unknown. In this study, a method using ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was established for the detection and identification of the metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang...
July 18, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28718992/melatonin-impedes-tet1-dependent-mglur5-promoter-demethylation-to-relieve-pain
#10
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Dylan Chou, Hsueh-Hsiao Wang, Gin-Den Chen, Tzer-Bin Lin, Hsien-Yu Peng
Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity...
July 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28718961/photodegradation-kinetics-transformation-and-toxicity-prediction-of-ketoprofen-carprofen-and-diclofenac-acid-in-aqueous-solutions
#11
Jian Li, Li-Yun Ma, Lu-Shuang Li, Li Xu
In this study, the photodegradation of three commonly used non-steroidal anti-inflammatory drugs, ketoprofen (KET), carprofen (CAR) and diclofenac acid (DIC), was conducted under UV irradiation. The kinetic results showed that the studied three pharmaceuticals obeyed to the first-order reaction with the decreasing rate constants of 1.54×10(-4) s(-1) , 5.91×10(-5) s(-1) and 7.78×10(-6) s(-1) for CAR, KET and DIC, respectively. Moreover, the main transformation products (TPs) were identified by ion-pair liquid-liquid extraction combined with injection port derivatization-gas chromatography-mass spectrometer and high performance liquidchromatography-quadrupole-time of flight mass spectrometer analysis...
July 18, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28718960/chemical-uplc-esi-ms-ms-profiling-of-aconitum-alkaloids-and-their-metabolites-in-rat-plasma-and-urine-after-oral-administration-of-aconitum-carmichaelii-debx-root-extract
#12
Mingjie Zhang, Manman Wang, Jiajia Liang, Yongqing Wen, Zhili Xiong
In this paper, an ultra high performance liquid chromatography tandem mass spectrometric (UPLC-ESI-MS/MS) method in positive ion mode was established to systematically identify and to compare the major aconitum alkaloids and their metabolites in rat plasma and urine after oral administration of Fuzi extract. A total twenty-nine components including twenty-five C19 -diterpenoid alkaloids and four C20 -diterpenoid alkaloids were identified in Fuzi extract. Thirteen of the parent components and five metabolites were detected in rat plasma and sixteen parent compounds and six metabolites in urine...
July 18, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28716728/cytochrome-p450-3a-selectively-affects-the-pharmacokinetic-interaction-between-erlotinib-and-docetaxel-in-rats
#13
Xuan Qin, Jian Lu, Peili Wang, Peipei Xu, Mingyao Liu, Xin Wang
Erlotinib as a first-line drug is used in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations, while resistance to this drug will occur after several years of treatment. Therefore, the microtubule disturber docetaxel is introduced as combined regimen in clinical trials. This report investigated the potentials and mechanisms of drug-drug interaction (DDI) between erlotinib and docetaxel using wild type (WT) and Cyp3a1/2 knockout (KO) rats. The erlotinib O-demethylation and docetaxel hydroxylation reactions in the absence or the presence of another drug were analyzed in vitro via the assay of rat liver microsomes...
July 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28715893/5-formyl-and-5-carboxydeoxycytidines-do-not-cause-accumulation-of-harmful-repair-intermediates-in-stem-cells
#14
René Rahimoff, Olesea Kosmatchev, Angie Kirchner, Toni Pfaffeneder, Fabio Spada, Victor Brantl, Markus Müller, Thomas Carell
5-Formyl-dC (fdC) and 5-carboxy-dC (cadC) are newly discovered bases in the mammalian genome that are supposed to be substrates for base excision repair (BER) in the framework of active demethylation. The bases are recognized by the monofunctional thymine DNA glycosylase (Tdg), which cleaves the glycosidic bond of the bases to give potentially harmful abasic sites (AP-sites). Because of the turnover of fdC and cadC during cell state transitions, it is an open question to what extent such harmful AP-sites may accumulate during these processes...
July 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28714938/taxifolin-activates-the-nrf2-anti-oxidative-stress-pathway-in-mouse-skin-epidermal-jb6-p-cells-through-epigenetic-modifications
#15
Haixue Kuang, Zhenqiu Tang, Chengyue Zhang, Zhibin Wang, Wenji Li, Chunjuan Yang, Qiuhong Wang, Bingyou Yang, Ah-Ng Kong
Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28714348/two-new-14-15-secopregnane-type-steroidal-glycosides-from-the-roots-of-cynanchum-limprichtii
#16
Jia-Chuan Liu, Li-Li Yu, Shao-Fei Chen, Xiao-Jie Lu, Dan Zhao, Hai-Feng Wang, Gang Chen, Yue-Hu Pei
Two new steroidal glycosides 1 and 2, along with three known ones (3-5), were isolated from the 95% ethanol extract of the roots of Cynanchum limprichtii Schltr. The structure of the new compounds was elucidated as 3-O-α-L-diginopyranosyl-(1→4)-β-D-digitoxopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-thevetopyranosyl-14, 16:15, 20:18, 20-triepoxy-14, 15-secopregn-4, 6, 8 (14)-triene (1) and 3-O-α-L-cymaropyranosyl-(1→4)-β-D-digitoxopyranosyl- (1→4)-β-D-3-demethyl-2-deoxythevetopyranosyl-14, 16: 15, 20: 8, 20-triepoxy-14, 15-secopregn-5, 8 (14)-diene (2) on the basis of spectroscopic analysis together with acidic hydrolysis...
July 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28709726/induction-and-maintenance-of-regulatory-t-cells-by-transcription-factors-and-epigenetic-modifications
#17
REVIEW
Mana Iizuka-Koga, Hiroko Nakatsukasa, Minako Ito, Takashi Akanuma, Qianjin Lu, Akihiko Yoshimura
Regulatory T cells (Tregs) are an essential cell subset for the maintenance of immune homeostasis. Foxp3 (Forkhead box P3) is the Treg master gene which is essential for immune suppressing activity. In addition, Tregs are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory genes. The molecular mechanisms of Treg development and maintenance have been intensively investigated. Tregs are characterized by expression of the transcription factor Foxp3...
July 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28707409/chilling-responsive-demeter-like-dna-demethylase-mediates-in-poplar-bud-break
#18
Daniel Conde, Anne-Laure Le Gac, Mariano Perales, Christopher Dervinis, Matias Kirst, Stéphane Maury, Pablo González-Melendi, Isabel Allona
Annual dormancy-growth cycle is a developmental and physiological process essential for the survival of deciduous trees in temperate and boreal forests. Seasonal control of shoot growth in woody perennials requires specific genetic programs responding to environmental signals. The environmental-controlled mechanisms that regulate the shift between winter dormancy and the growth promoting genetic programs are still unknown. Here, we show that dynamics in genomic DNA (gDNA) methylation levels are involved in the regulation of dormancy-growth cycle in poplar...
July 13, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28706564/vitamin-c-induces-specific-demethylation-of-h3k9me2-in-mouse-embryonic-stem-cells-via-kdm3a-b
#19
Kevin T Ebata, Kathryn Mesh, Shichong Liu, Misha Bilenky, Alexander Fekete, Michael G Acker, Martin Hirst, Benjamin A Garcia, Miguel Ramalho-Santos
BACKGROUND: Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. RESULTS: We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in naïve ES cells...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28706011/increased-ifn-%C3%AE-t-cells-are-responsible-for-the-clinical-responses-of-low-dose-dna-demethylating-agent-decitabine-anti-tumor-therapy
#20
Xiang Li, Yan Zhang, Meixia Chen, Qian Mei, Yang Liu, Kai-Chao Feng, Hejin Jia, Liang Dong, Lu Shi, Lin Liu, Jing Nie, Weidong Han
Low-dose DNA demethylating agent decitabine therapy is effective in a subgroup of cancer patients. It remains largely elusive for the biomarker to predict therapeutic response and the underlying anti-tumor mechanisms, especially the impact on host anti-tumor immunity.<br />Experimental Design: The influence of low-dose decitabine on T cells was detected both in vitro and in vivo Moreover, a test cohort and a validation cohort of advanced solid tumor patients with low-dose decitabine-based treatment were involved...
July 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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