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Demethylation

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https://www.readbyqxmd.com/read/28225433/the-role-of-5-hydroxymethylcytosine-in-melanoma
#1
Feng-Juan Li, Li-Ming Li, Rui-Hua Zhang, Cui Xu, Pan Zhou, Jia Long, Gang Hu, Ming-Jun Jiang
Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation...
February 20, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28224016/characterization-of-major-metabolites-of-polymethoxylated-flavonoids-in-pericarpium-citri-reticulatae-using-liver-microsomes-immobilized-on-magnetic-nanoparticles-coupled-with-uplc-ms-ms
#2
Jun Lei, Ying Xue, Yi-Ming Liu, Xun Liao
The peels of citrus fruits (Pericarpium Citri Reticulatae, PCR) have long been used in traditional Chinese medicines (TCMs). Polymethoxylated flavonoids (PMFs) were found to be the main components present in PCR extracts, but their metabolism remains unclear which restrain the utilization of this TCM. In the present work, rat liver microsomes were immobilized on magnetic nanoparticles (LMMNPs) for in vitro metabolic study on the whole PMFs of PCR. LMMNPs were characterized by transmission electron microscope and Fourier-transform infrared spectrum...
2017: Chemistry Central Journal
https://www.readbyqxmd.com/read/28219935/novel-insights-into-gastric-cancer-methylation-of-r-spondins-and-regulation-of-lgr5-by-sp1
#3
Franziska Wilhelm, Eva Simon, Christine Boger, Hans-Michael Behrens, Sandra Kruger, Christoph Rocken
: Recently it was shown that leucine-rich repeat-containing receptor 5 (LGR5) expressing stem cells are the cellular origin of intestinal-type gastric cancer. The aim of our study was to uncover regulatory mechanisms of LGR5 expression in gastric mucosa and their implications for cancer development. Reporter assays identified a LGR5 promoter fragment, which is highly relevant for active LGR5 expression. Chromatin immunoprecipitation (ChIP) verified that SP1 is bound within this region and reporter activity increased in SP1 transfected cells...
February 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28219743/significant-association-of-cyp19a-promoter-methylation-with-environmental-factors-and-gonadal-differentiation-in-olive-flounder-paralichthys-olivaceus
#4
Zhaofei Fan, Yuxia Zou, Shuang Jiao, Xungang Tan, Zhihao Wu, DongDong Liang, Peijun Zhang, Feng You
The sex ratio of olive flounder Paralichthys olivaceus is sensitive to temperature or exogenous hormone exposures in the period of gonadal differentiation. Among sex-related genes, cyp19a, encoding cytochrome P450 aromatase,exhibits significant sex-dimorphic expression pattern and plays an important role in fish gonadal differentiation and development. The present study investigated the expression levels and promoter methylation dynamics of cyp19a and its regulators (nr5a2 and nr0b1), and sex-steroid hormone levels during flounder gonadal differentiation under the treatments of high temperature and estradiol-17β (E2)...
February 17, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28219444/a-functional-snp-associated-with-atopic-dermatitis-controls-cell-type-specific-methylation-of-the-vstm1-gene-locus
#5
Dilip Kumar, Kia Joo Puan, Anand Kumar Andiappan, Bernett Lee, Geertje H A Westerlaken, Doreen Haase, Rossella Melchiotti, Zhuang Li, Nurhashikin Yusof, Josephine Lum, Geraldine Koh, Shihui Foo, Joe Yeong, Alexessander Couto Alves, Juha Pekkanen, Liang Dan Sun, Astrid Irwanto, Benjamin P Fairfax, Vivek Naranbhai, John E A Common, Mark Tang, Chin Keh Chuang, Marjo-Riitta Jarvelin, Julian C Knight, Xuejun Zhang, Fook Tim Chew, Shyam Prabhakar, Liu Jianjun, De Yun Wang, Francesca Zolezzi, Michael Poidinger, E Birgitte Lane, Linde Meyaard, Olaf Rötzschke
BACKGROUND: Expression quantitative trait loci (eQTL) databases represent a valuable resource to link disease-associated SNPs to specific candidate genes whose gene expression is significantly modulated by the SNP under investigation. We previously identified signal inhibitory receptor on leukocytes-1 (SIRL-1) as a powerful regulator of human innate immune cell function. While it is constitutively high expressed on neutrophils, on monocytes the SIRL-1 surface expression varies strongly between individuals...
February 20, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28219126/-clinical-significance-of-hypermethylation-of-dlc-1-gene-in-myelodysplastic-syndrome-patients-and-effects-of-decitabine-on-dlc-1-gene-expression
#6
H Y Fu, H R Zhou, J G Yan, C J Chen, J Z Shen
Objective: To detect the methylation status of DLC-1 gene in the patients with myelodysplastic syndrome(MDS), the effect of abnormal methylation of DLC-1 gene on the expression of DLC-1 gene, the clinical significance of methylation of DLC-1 gene in MDS patients, and the effect of decitabine on DLC-1 gene expression. Methods: A total of 43 MDS patients were treated in Fujian Medical University Union Hospital from 2013 to 2015. Methylation status of DLC-1 gene in MDS patients were detected by the methylation specific PCR(MSP)...
February 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28218430/stepwise-assembly-of-functional-c-terminal-rest-nrsf-transcriptional-repressor-complexes-as-a-drug-target
#7
Ken Inui, Zongpei Zhao, Juan Yuan, Sakthidasan Jayaprakash, Le T M Le, Srdja Drakulic, Bjoern Sander, Monika M Golas
In human cells, thousands of predominantly neuronal genes are regulated by the repressor element 1 (RE1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF). REST/NRSF represses transcription of these genes in stem cells and non-neuronal cells by tethering corepressor complexes. Aberrant REST/NRSF expression and intracellular localization are associated with cancer and neurodegeneration in humans. To date, detailed molecular analyses of REST/NRSF and its C-terminal repressor complex have been hampered largely by the lack of sufficient amounts of purified REST/NRSF and its complexes...
February 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28218039/demethylation-and-alterations-in-the-expression-level-of-the-cell-cycle-related-genes-as-possible-mechanisms-in-arsenic-trioxide-induced-cell-cycle-arrest-in-human-breast-cancer-cells
#8
Farima Moghaddaskho, Haniyeh Eyvani, Mohsen Ghadami, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Arsenic trioxide (As2O3) has been used clinically as an anti-tumor agent. Its mechanisms are mostly considered to be the induction of apoptosis and cell cycle arrest. However, the detailed molecular mechanisms of its anti-cancer action through cell cycle arrest are poorly known. Furthermore, As2O3 has been shown to be a potential DNA methylation inhibitor, inducing DNA hypomethylation. We hypothesize that As2O3 may affect the expression of cell cycle regulatory genes by interfering with DNA methylation patterns...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28215635/mechanical-stimulation-promote-the-osteogenic-differentiation-of-bone-marrow-stromal-cells-through-epigenetic-regulation-of-sonic-hedgehog
#9
Chuandong Wang, Shengzhou Shan, Chenglong Wang, Jing Wang, Jiao Li, Guoli Hu, Kerong Dai, Qingfeng Li, Xiaoling Zhang
Mechanical unloading leads to bone loss and disuse osteoporosis partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro. Besides, we found that Hedgehog (Hh) signaling pathway was activated in this process. Inhibition of which by either knockdown of Sonic hedgehog (Shh) or treating BMSCs with Hh inhibitors attenuated the osteogenic effect of CMS on BMSCs, suggesting that Hh signaling pathway acts as an endogenous mediator of mechanical stimuli on BMSCs...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28214648/toxicity-degradation-and-metabolic-fate-of-ibuprofen-on-freshwater-diatom-navicula-sp
#10
Tengda Ding, Mengting Yang, Junmin Zhang, Bo Yang, Kunde Lin, Juying Li, Jay Gan
Ibuprofen (IBU) is one of the most widely used and frequently detected human pharmaceuticals in aquatic environment. However, the toxicity of IBU on diatom and its fate remain still unkown. In the present study, the toxicity of IBU on the diatom was evaluated by the algal growth rate, the chlorophyll-a and carotenoids contents. The degradation of IBU including in particular the potential for the formation of incomplete degradation products was also explored. Biochemical characteristics of Navicula sp. were significantly inhibited at IBU concentrations up to 50mgL(-1) after 10days of exposure...
February 6, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28214647/fate-of-antimicrobials-in-duckweed-lemna-minor-wastewater-treatment-systems
#11
Evangelia I Iatrou, Georgia Gatidou, Dimitrios Damalas, Nikolaos S Thomaidis, Athanasios S Stasinakis
The fate of four antimicrobials (cefadroxil, CFD; metronidazole, METRO; trimethoprim, TRI; sulfamethoxazole, SMX) was studied in Lemna minor systems and the role of different mechanisms on their removal was evaluated. All micropollutants were significantly removed in batch experiments with active Lemna minor; the highest removal was observed for CFD (100% in 14 d), followed by METRO (96%), SMX (73%) and TRI (59%) during 24 d of the experiment. Calculation of kinetic constants for hydrolysis, photodegradation, sorption to biomass and plant uptake revealed significant differences depending on the compound and the studied mechanism...
February 13, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28214075/asymmetric-total-synthesis-of-tetrahydroprotoberberine-derivatives-and-evaluation-of-their-binding-affinities-at-dopamine-receptors
#12
David Y W Lee, Jing Liu, Shuzhen Zhang, Peng Huang, Lee-Yuan Liu-Chen
Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. l-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites l-ICP, l-CD, and l-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors...
January 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28213207/epimetabolites-discovering-metabolism-beyond-building-and-burning
#13
REVIEW
Megan R Showalter, Tomas Cajka, Oliver Fiehn
Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include regulation of histone demethylation in epigenetics, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, stem cell pluripotency status, inhibition of nitric oxide signaling and others. Such modified compounds, defined as epimetabolites, have functions distinct from classic hormones as well as removed from generic anabolism and catabolism...
February 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28212330/synthesis-of-8-aryl-o-methylcyanidins-and-their-usage-for-dye-sensitized-solar-cell-devices
#14
Yuki Kimura, Kin-Ichi Oyama, Yasujiro Murata, Atsushi Wakamiya, Kumi Yoshida
Anthocyanins as natural pigments are colorful and environmentally compatible dyes for dye-sensitized solar cells (DSSCs). To increase the efficiency, we designed and synthesized unnatural O-methylflavonols and O-methylcyanidins that possess an aryl group at the 8-position. We synthesized per-O-methylquercetin from quercetin, then using selective demethylation prepared various O-methylquercetins. Using the Suzuki-Miyaura coupling reaction, 8-arylation of per-O-methylquercetin was achieved. Using a LiAlH₄ reduction or Clemmensen reduction, these flavonols were transformed to the corresponding cyanidin derivatives in satisfactory yields...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28211698/demethylation-of-polymethoxyflavones-by-human-gut-bacterium-blautia-sp-mrg-pmf1
#15
Supawadee Burapan, Mihyang Kim, Jaehong Han
Polymethoxyflavones (PMFs) were biotransformed to various demethylated metabolites in the human intestine by the PMF-metabolizing bacterium, Blautia sp. MRG-PMF1. Because the newly formed metabolites can have different biological activities, the pathways and regioselectivity of PMF bioconversion were investigated. Using an anaerobic in vitro study, 12 PMFs, 5,7-dimethoxyflavone (5,7-DMF), 5-hydroxy-7-methoxyflavone (5-OH-7-MF), 3,5,7-trimethoxyflavone (3,5,7-TMF), 5-hydroxy-3,7-dimethoxyflavone (5-OH-3,7-DMF), 5,7,4'-trimethoxyflavone (5,7,4'-TMF), 5-hydroxy-7,4'-dimethoxyflavone (5-OH-7,4'-DMF), 3,5,7,4'-tetramethoxyflavone (3,5,7,4'-TMF), 5-hydroxy-3,7,4'-trimethoxyflavone (5-OH-3,7,4'-TMF), 5,7,3',4'-tetramethoxyflavone (5,7,3',4'-TMF), 3,5,7,3',4'-pentamethoxyflavone (3,5,7,3',4'-PMF), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (5-OH-3,7,3',4'-TMF), and 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (5,3'-diOH-3,7,4'-TMF), were converted to chrysin, apigenin, galangin, kaempferol, luteolin, and quercetin after complete demethylation...
February 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28209718/demethylation-of-h3k27-is-essential-for-the-induction-of-direct-cardiac-reprogramming-by-mir-combo
#16
Sophie Dal-Pra, Conrad P Hodgkinson, Maria Mirotsou, Imke Kirste, Victor J Dzau
Rationale: Direct reprogramming of cardiac fibroblasts to cardac omyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of four microRNAs (miR-1, miR-133, miR-208 and miR-499) that we named miR combo. However, the mechanism of miR combo mediated direct cardiac reprogramming is currently unknown. Objective: Here we investigated the possibility that miR combo initiated direct cardiac reprogramming through an epigenetic mechanism...
February 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28209170/lincrnafezf1-as1-represses-p21-expression-to-promote-gastric-cancer-proliferation-through-lsd1-mediated-h3k4me2-demethylation
#17
Yan-Wen Liu, Rui Xia, Kai Lu, Min Xie, Fen Yang, Ming Sun, Wei De, Cailian Wang, Guozhong Ji
BACKGROUND: Although the prognosis of gastric cancer patients have a favorable progression, there are some patients with unusual patterns of locoregional and systemic recurrence. Therefore, a better understanding of early molecular events of the disease is needed. Current evidences demonstrate that long noncoding RNAs (lncRNAs) may be an important class of functional regulators involved in human gastric cancers development. Our previous studies suggest that HOTAIR contributes to gastric cancer development, and the overexpression of HOTAIR predicts a poor prognosis...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28208656/primetime-for-learning-genes
#18
REVIEW
Joyce Keifer
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28205560/alkb-homolog-3-mediated-trna-demethylation-promotes-protein-synthesis-in-cancer-cells
#19
Yuko Ueda, Ikumi Ooshio, Yasuyuki Fusamae, Kaori Kitae, Megumi Kawaguchi, Kentaro Jingushi, Hiroaki Hase, Kazuo Harada, Kazumasa Hirata, Kazutake Tsujikawa
The mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205258/simultaneous-quantification-of-antofloxacin-and-its-major-metabolite-in-human-urine-by-hplc-ms-ms-and-its-application-to-a-pharmacokinetic-study
#20
Yunsu Ma, Qianru Wang, Hongwen Zhang, Lijun Xie, Juan Chen, Mao Huang, Yun Liu, Yuanyuan Wang, Libin Wang, Luning Sun, Ning Ou
This study presents a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of antofloxacinin and its main metabolite-N-demethylated metabolite (N-DM) in human urine, ornidazole was used as the internal standard (IS). This was a clinical urine recovery study, in which 10 healthy Chinese volunteers were intravenously administered a single 200 mg antofloxacin hydrochloride. Compounds were extracted by albumen precipitation, after which, samples were isocratic eluted by a Poroshell 120 SB-C18 column, and were analysed using HPLC-MS/MS under electronic spray ionization (ESI) positive ion mode...
February 16, 2017: Biomedical Chromatography: BMC
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