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Demethylation

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https://www.readbyqxmd.com/read/28634398/mutations-in-human-aid-differentially-affect-its-ability-to-deaminate-cytidine-and-5-methylcytidine-in-ssdna-substrates-in-vitro
#1
Lucyna Budzko, Paulina Jackowiak, Karol Kamel, Joanna Sarzynska, Janusz M Bujnicki, Marek Figlerowicz
Activation-induced cytidine deaminase (AID) is known for its established role in antibody production. AID induces the diversification of antibodies by deaminating deoxycytidine (C) within immunoglobulin genes. The capacity of AID to deaminate 5-methyldeoxycytidine (5 mC) and/or 5-hydroxymethyldeoxycytidine (5 hmC), and consequently AID involvement in active DNA demethylation, is not fully resolved. For instance, structural determinants of AID activity on different substrates remain to be identified. To better understand the latter issue, we tested how mutations in human AID (hAID) influence its ability to deaminate C, 5 mC, and 5 hmC in vitro...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633113/transformation-and-toxicity-assessment-of-two-uv-filters-using-uv-h2o2-process
#2
Mingguo Peng, Erdeng Du, Zhihong Li, Dongdong Li, Huajie Li
The treatment of two typical UV filters benzophenone-4 (BP4) and benzophenone-9 (BP9) was evaluated in aqueous solutions by UV/H2O2 process. High-resolution accurate mass spectrometry (HRMS) was used to identify the degradation intermediates. A total of 12 BP4 degradation products and 17 BP9 degradation products were identified. A series of OH-initiated reactions, including hydroxylation, dihydroxylation, decarboxylation, demethylation, and ring breaking, lead to the final mineralization of BP4 and BP9. The degradation mechanisms of BP4 and BP9 are also proposed, separately...
June 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28627644/5%C3%A2-aza%C3%A2-2-%C3%A2-deoxycytidine-promotes-migration-of-acute-monocytic-leukemia-cells-via-activation-of-ccl2%C3%A2-ccr2%C3%A2-erk-signaling-pathway
#3
Xia Xiao, Qian Xu, Yan Sun, Ziwei Lu, Rui Li, Xinxin Wang, Xin Jiang, Guirong Zhang, Yechen Xiao
5-aza‑2'-deoxycytidine (5-Aza) has been approved for clinical use in the treatment of myelodysplastic syndrome and acute myeloid leukemia (AML). It inhibits cell proliferation and induces cell differentiation by demethylating various genes, including tumor suppressor genes, transcription factors, and genes encoding cell cycle inhibitors. Although it has demonstrated efficacy in the clinic, drug resistance following 5‑Aza treatment occurs. Cell migration and invasion following 5‑Aza treatment are considered to be the key factors underlying drug resistance; however, there is currently limited information regarding the detailed mechanisms involved...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627269/profiling-and-identification-of-chlorogenic-acid-metabolites-in-rats-by-ultra-high-performance-liquid-chromatography-coupled-with-linear-ion-trap-orbitrap-mass-spectrometer
#4
Fei Wang, Zhanpeng Shang, Lulu Xu, Zhibin Wang, Wenjing Zhao, XiaoDan Mei, Jianqiu Lu, Jiangyu Zhang
1. Chlorogenic acids (CGAs), one kind of major bioactive constituents isolated from Flos Lonicerae Japonicae, possess many biological activities, such as antibacterial, antioxidant, and antiviral activities. In this study, we established an efficient strategy using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of CGAs in rat urine and plasma. 2. The extract from Flos Lonicerae Japonicae was orally administrated to Sprague-Dawley (SD) rats at a dose of 1000 mg/kg body weight...
June 19, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28624458/dna-hypomethylation-circuit-of-mouse-rdna-repeats-in-the-germ-cell-lineage
#5
Asuka Furuta, Toshinobu Nakamura
DNA methylation is dynamically reprogrammed at two developmental periods, in primordial germ cells and pre-implantation embryos, via distinct phases of DNA demethylation and de novo methylation. Here we show that ribosomal DNA (rDNA) promoters are hypomethylated in sperm and oocytes; this hypomethyaltion was maintained during pre-implantation development. A DNA methylation analysis of embryonic and extra-embryonic cells on embryonic day 7.5 (E7.5) revealed that the rDNA promoter was slightly methylated in embryonic and extra-embryonic regions...
June 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28623785/in-vitro-studies-on-nobiletin-isolated-from-citrus-plants-and-the-bioactive-metabolites-inhibitory-action-against-gelatinase-enzymatic-activity-and-the-molecular-mechanisms-in-human-retinal-m%C3%A3-ller-cell-line
#6
Yoshiki Miyata, Terumasa Nagase, Yoshiya Katsura, Hideyo Takahashi, Hideaki Natsugari, Tetsuta Oshitari, Hiroshi Kosano
Diabetic retinopathy (DR) is the most common cause of vision loss in patients with diabetes mellitus. Despite the presence of effective therapy, DR is still a significant health burden. A recent research suggests that matrix metalloproteinases (MMPs) could be promising targets, which exert multiple actions on early- and late-stage pathogenesis of DR. Among the MMP family, gelatinases (MMP-2 and MMP-9) act as potent proinflammatory, proangiogenic, and pro-apoptotic factors. Therefore, the pharmacological inhibitory effect of gelatinases on retinal MMP-producing cells may be useful in the treatment or prevention of DR...
June 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28623356/high-risk-human-papillomavirus-e7-alters-host-dna-methylome-and-represses-hla-e-expression-in-human-keratinocytes
#7
Louis Cicchini, Rachel Z Blumhagen, Joseph A Westrich, Mallory E Myers, Cody J Warren, Charlotte Siska, David Raben, Katerina J Kechris, Dohun Pyeon
Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokine CXCL14 and suppression of antitumor immune responses. To investigate the extent of gene expression dysregulated by HPV E7-induced DNA methylation, we analyzed parallel global gene expression and DNA methylation using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, and NIKS-16∆E7...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621778/synthesis-of-functionalized-alkyl-substituted-benzoquinones-by-rh-catalyzed-additions-of-boronic-acids
#8
Marcos Veguillas, Jaime Rojas-Martín, María Ribagorda, M Carmen Carreño
A general synthetic route to γ-oxo alkyl or α-hydroxy benzyl 2-substituted benzoquinones has been developed through a one-pot Rh-catalyzed C-C bond formation/oxidative demethylation sequence from 2,5-dimethoxy aryl boronic acids and several electron deficient alkenes or aldehydes. The process allows rapid access to functionalized benzoquinones under very mild conditions and good yields. We disclose the first example of a Rh-catalyzed 1,4-addition reaction of benzoquinonyl boronic acid to methyl vinyl ketone and other conjugate acceptors, which allows the direct synthesis of 2-(γ-functionalized alkyl) substituted benzoquinones...
June 16, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28621487/simultaneous-quantification-of-imatinib-and-its-main-metabolite-n-demethyl-imatinib-in-human-plasma-by-liquid-chromatography-tandem-mass-spectrometry-and-its-application-to-therapeutic-drug-monitoring-in-patients-with-gastrointestinal-stromal-tumor
#9
Wei Zhuang, Hai-Bo Qiu, Xin-Meng Chen, Xiu-Hong Yuan, Li-Fang Yang, Xiao-Wei Sun, Xiao-Jun Zhou, Min Huang, Xue-Ding Wang, Zhi-Wei Zhou
AIM: To improve and validate a more stable and less time-consuming method based on liquid chromatography and tandem mass spectrometry (LC- MS/MS) for the quantitative measurement of Imatinib and its metabolite N-demethyl-Imatinib (NDI) in human plasma. METHODS: Separation of analytes was performed on a Waters XTerra RP18 column (50mm×2.1 mm i.d., 3.5 μm) with a mobile phase consisting of methanol/acetonitrile/ water (65:20:15, v/v/v) with 0.05% formic acid at a flow-rate of 0...
June 16, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28621329/single-cell-multi-omics-sequencing-of-mouse-early-embryos-and-embryonic-stem-cells
#10
Fan Guo, Lin Li, Jingyun Li, Xinglong Wu, Boqiang Hu, Ping Zhu, Lu Wen, Fuchou Tang
Single-cell epigenome sequencing techniques have recently been developed. However, the combination of different layers of epigenome sequencing in an individual cell has not yet been achieved. Here, we developed a single-cell multi-omics sequencing technology (single-cell COOL-seq) that can analyze the chromatin state/nucleosome positioning, DNA methylation, copy number variation and ploidy simultaneously from the same individual mammalian cell. We used this method to analyze the reprogramming of the chromatin state and DNA methylation in mouse preimplantation embryos...
June 16, 2017: Cell Research
https://www.readbyqxmd.com/read/28621264/dna-methylation-hydroxymethylation-in-melanoma
#11
REVIEW
Siqi Fu, Haijing Wu, Huiming Zhang, Christine G Lian, Qianjin Lu
Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620234/ezh2-mediated-epigenetic-silencing-of-timp2-promotes-ovarian-cancer-migration-and-invasion
#12
Xiaoqing Yi, Jianfeng Guo, Jing Guo, Si Sun, Ping Yang, Junjie Wang, Yuan Li, Lisha Xie, Jing Cai, Zehua Wang
Enhancer of zeste homolog 2 (EZH2) is often increased in malignant tumors and is involved in metastasis. EZH2 silences gene expression by tri-methylating the lysine 27 residue of histone H3 (H3K27me3). However, the mechanism underlying EZH2 promotion of ovarian cancer metastasis remains elusive. Here, we showed that EZH2 is up-regulated in ovarian cancer and is associated with tumor metastasis and poor survival by mRNA sequencing and microarray results from databases. Tissue microarray and immunohistochemistry results revealed that EZH2 was negatively correlated with the expression of tissue inhibitor of metalloproteinases 2 (TIMP2)...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618166/abundance-genetic-diversity-and-sensitivity-to-demethylation-inhibitor-fungicides-of-aspergillus-fumigatus-isolates-from-organic-substrates-with-special-emphasis-on-compost
#13
Karin Santoro, Slavica Matić, Ulrich Gisi, Davide Spadaro, Massimo Pugliese, Maria L Gullino
BACKGROUND: Aspergillus fumigatus is a widespread fungus that colonizes dead organic substrates but it can also cause fatal human diseases. Aspergilloses are treated with demethylation inhibitor (DMI) fungicides; however, resistant isolates appeared recently in the medical but also environmental area. The present study aims at molecular characterizing and quantifying A. fumigatus in major environmental habitats and determining its sensitivity to medical and agricultural DMI fungicides...
June 15, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28607593/chemoresistance-of-colorectal-cancer-to-5-fluorouracil-is-associated-with-silencing-of-the-bnip3-gene-through-aberrant-methylation
#14
Jianming He, Li Pei, Heng Jiang, Weiwen Yang, Jianfang Chen, Houjie Liang
Purpose To investigate the correlation between chemoresistance of colorectal cancer to 5-fluorouracil and BNIP3 and the underlying mechanism. Methods BNIP3 protein in specimens was evaluated using immunohistochemistry. Semi-quantitative reverse transcription PCR and Western blot was employed to assay gene expression. The promoter methylation status of BNIP3 was examined by methylation-specific PCR. Drug sensitivity was assayed using MTT assay. Results Specimens from 81 patients with colorectal cancer receiving 5-fluorouracil-based chemotherapy were analyzed...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28607180/p53-is-essential-for-dna-methylation-homeostasis-in-na%C3%A3-ve-embryonic-stem-cells-and-its-loss-promotes-clonal-heterogeneity
#15
Ayala Tovy, Adam Spiro, Ryan McCarthy, Zohar Shipony, Yael Aylon, Kendra Alton, Elena Ainbinder, Noa Furth, Amos Tanay, Michelle Barton, Moshe Oren
DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in naïve mouse ESCs (mESCs), p53 restricts the expression of the de novo DNA methyltransferases Dnmt3a and Dnmt3b while up-regulating Tet1 and Tet2, which promote DNA demethylation. The DNA methylation imbalance in p53-deficient (p53(-/-)) mESCs is the result of augmented overall DNA methylation as well as increased methylation landscape heterogeneity...
June 12, 2017: Genes & Development
https://www.readbyqxmd.com/read/28602505/proposal-of-5-methoxy-n-methyl-n-isopropyltryptamine-consumption-biomarkers-through-identification-of-in-vivo-metabolites-from-mice
#16
D Fabregat-Safont, M Barneo-Muñoz, F Martinez-Garcia, J V Sancho, F Hernández, M Ibáñez
New psychoactive substances (NPS) are a new breed of synthetically produced substances designed to mimic the effects of traditional illegal drugs. Synthetic cannabinoids and synthetic cathinones are the two most common groups, which try to mimic the effects of the natural compounds (9)Δ-tetrahydrocannabinol and cathinone, respectively. Similarly, synthetic tryptamines are designer compounds which are based on the compounds psilocin, N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine found in some mushrooms...
June 5, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28601635/silencing-hif-1%C3%AE-induces-tet2-expression-and-augments-ascorbic-acid-induced-5-hydroxymethylation-of-dna-in-human-metastatic-melanoma-cells
#17
Adam P Fischer, Sarah L Miles
Expression and function of Ten-eleven translocation (TET) enzymes, which initiate DNA demethylation by catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5 hmC) on methylated DNA, are frequently lost in malignant tissue. This ultimately results in lost expression of methylated tumor suppressor genes. Many malignancies, including melanoma, also aberrantly overexpress the oncogenic hypoxia inducible factor-1α (HIF-1α) transcription factor, however the association between HIF-1α and TET enzyme expression is largely uninvestigated...
June 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28601046/lsd1-knockdown-reveals-novel-histone-lysine-methylation-in-human-breast-cancer-mcf-7-cells
#18
Yue Jin, Bo Huo, Xueqi Fu, Zhongyi Cheng, Jun Zhu, Yu Zhang, Tian Hao, Xin Hu
Histone lysine methylation, which plays an important role in the regulation of gene expression, genome stability, chromosome conformation and cell differentiation, is a dynamic process that is collaboratively regulated by lysine methyltransferases (KMTs) and lysine demethylases (KDMs). LSD1, the first identified KDMs, catalyzes the demethylation of mono- and di-methylated H3K4 and H3K9. Here, we systematically investigated the effects of LSD1 knockdown on histone methylations. Surprisingly, in addition to H3K4 and H3K9, the methylation level on other histone lysines, such as H3K27, H3K36 and H3K79, are also increased...
June 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28600501/hatching-enzymes-disrupt-aberrant-gonadal-degeneration-by-the-autophagy-apoptosis-cell-fate-decision
#19
Tapas Chakraborty, Sipra Mohapatra, Megumi Tobayama, Kayoko Ohta, Yong-Woon Ryu, Yukinori Kazeto, Kohei Ohta, Linyan Zhou, Yoshitaka Nagahama, Takahiro Matsubara
Environmental stressors, gonadal degenerative diseases and tumour development can significantly alter the oocyte physiology, and species fertility and fitness. To expand the molecular understanding about oocyte degradation, we isolated several spliced variants of Japanese anchovy hatching enzymes (AcHEs; ovastacin homologue) 1 and 2, and analysed their potential in oocyte sustenance. Particularly, AcHE1b, an ovary-specific, steroid-regulated, methylation-dependent, stress-responsive isoform, was neofunctionalized to regulate autophagic oocyte degeneration...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600287/enrichment-of-human-ccr6-regulatory-t-cells-with-superior-suppressive-activity-in-oral-cancer
#20
Jang-Jaer Lee, Kung-Chi Kao, Yen-Ling Chiu, Chiau-Jing Jung, Chung-Ji Liu, Shih-Jung Cheng, Yen-Liang Chang, Jenq-Yuh Ko, Jean-San Chia
Human oral squamous cell carcinoma (OSCC) constitutes an inflammatory microenvironment enriched with chemokines such as CCL20, which promote cancer cell invasion and tumor progression. We found that in OSCC there is a correlation between the expression of CCL20 and FOXP3 mRNA. Therefore, we hypothesized that OSCC may favor the recruitment and retention of regulatory T (Treg) cells that express the CCL20 receptor, CCR6. Interestingly, most (∼60%) peripheral blood Treg cells express CCR6, and CCR6(+) Treg cells exhibit an activated effector/memory phenotype...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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