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Demethylation

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https://www.readbyqxmd.com/read/29150948/methylation-associated-dok1-and-dok2-down-regulation-potential-biomarkers-for-predicting-adverse-prognosis-in-acute-myeloid-leukemia
#1
Pin-Fang He, Zi-Jun Xu, Jing-Dong Zhou, Xi-Xi Li, Wei Zhang, De-Hong Wu, Zhi-Hui Zhang, Xin-Yue Lian, Xin-Yu Yao, Zhao-Qun Deng, Jiang Lin, Jun Qian
DOK-1 and DOK-2 (DOK1/2) are closely related members of downstream of tyrosine kinase (DOK) family genes, which are found to be frequently rearranged in several hematopoietic cancers. However, the clinical implications of DOK1/2 in acute myeloid leukemia (AML) remain largely unknown. To investigate the clinical significance, real-time quantitative PCR (RQ-PCR) was carried out to detect DOK1/2 expressions in 125 de novo AML patients and 28 healthy controls. Real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP) were applied to detect DOK1/2 methylation level and density...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29149454/melatonin-alleviates-adipose-inflammation-through-elevating-%C3%AE-ketoglutarate-and-diverting-adipose-derived-exosomes-to-macrophages-in-mice
#2
Zhenjiang Liu, Lu Gan, Tiantian Zhang, Qian Ren, Chao Sun
Obesity is associated with macrophage infiltration and metabolic inflammation, both of which promote metabolic disease progression. Melatonin is reported to possess anti-inflammatory properties by inhibiting inflammatory response of adipocytes and macrophages activation. However, the effects of melatonin on the communication between adipocytes and macrophages during adipose inflammation remain elusive. Here, we demonstrated melatonin alleviated inflammation and elevated α-ketoglutarate (αKG) level in adipose tissue of obese mice...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29146253/isolation-and-characterisation-of-theobromine-degrading-filamentous-fungi
#3
Daniel Oduro-Mensah, Augustine Ocloo, Sammy T Lowor, Evelyn Y Bonney, Laud K N A Okine, Naa Ayikailey Adamafio
Strategies for achieving global food security include identification of alternative feedstock for use as animal feed, to contribute towards efforts at increasing livestock farming. The presence of theobromine in cocoa pod husks, a major agro-waste in cocoa-producing countries, hinders its utilisation for this purpose. Cheap treatment of cocoa pod husks to remove theobromine would allow largescale beneficial use of the millions of metric tonnes generated annually. The aim of this study was to isolate theobromine-degrading filamentous fungi that could serve as bioremediation agents for detheobromination of cocoa pod husks...
January 2018: Microbiological Research
https://www.readbyqxmd.com/read/29144498/corrigendum-the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#4
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
This corrects the article DOI: 10.1038/ni.3830.
November 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29143918/induction-of-cd4-cd25-foxp3-regulatory-t-cells-by-mesenchymal-stem-cells-is-associated-with-runx-complex-factors
#5
Maryam Khosravi, Ali Bidmeshkipour, Ali Moravej, Suzzan Hojjat-Assari, Sina Naserian, Mohammad Hossein Karimi
Among the particular immunomodulation properties of mesenchymal stem cells (MSCs), one relies on their capacity to regulatory T cell (Treg) induction from effector T cells. Stable expression of Foxp3 has a dominant role in suppressive phenotype and stability of induced regulatory T cells (iTregs). How MSCs induce stable Foxp3 expression in iTregs remains unknown. We previously showed MSCs could enhance demethylation of Treg-specific demethylated region (TSDR) in iTregs in cell-cell contact manner (unpublished data)...
November 16, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29141958/dna-methylation-defines-regional-identity-of-human-intestinal-epithelial-organoids-and-undergoes-dynamic-changes-during-development
#6
Judith Kraiczy, Komal M Nayak, Kate J Howell, Alexander Ross, Jessica Forbester, Camilla Salvestrini, Roxana Mustata, Sally Perkins, Amanda Andersson-Rolf, Esther Leenen, Anke Liebert, Ludovic Vallier, Philip C Rosenstiel, Oliver Stegle, Gordon Dougan, Robert Heuschkel, Bon-Kyoung Koo, Matthias Zilbauer
OBJECTIVE: Human intestinal epithelial organoids (IEOs) are increasingly being recognised as a highly promising translational research tool. However, our understanding of their epigenetic molecular characteristics and behaviour in culture remains limited. DESIGN: We performed genome-wide DNA methylation and transcriptomic profiling of human IEOs derived from paediatric/adult and fetal small and large bowel as well as matching purified human gut epithelium. Furthermore, organoids were subjected to in vitro differentiation and genome editing using CRISPR/Cas9 technology...
November 15, 2017: Gut
https://www.readbyqxmd.com/read/29139326/dna-polymerase-%C3%AE-mutational-signatures-are-found-in-a-variety-of-different-types-of-cancer
#7
Igor B Rogozin, Alexander Goncearenco, Artem G Lada, Subhajyoti De, German Nudelman, Anna R Panchenko, David N Cooper, Youri I Pavlov
DNA polymerase (pol) η is a specialized error-prone polymerase with at least two quite different and contrasting cellular roles: to mitigate the genetic consequences of solar UV irradiation, and promote somatic hypermutation in the variable regions of immunoglobulin genes. Misregulation and mistargeting of pol η can compromise genome integrity. We explored whether the mutational signature of pol η could be found in datasets of human somatic mutations derived from normal and cancer cells. A substantial excess of single and tandem somatic mutations within known pol η mutable motifs was noted in skin cancer as well as in many other types of human cancer, suggesting that somatic mutations in A:T bases generated by DNA polymerase η are a common feature of tumorigenesis...
November 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29137406/the-forkhead-box-c1-foxc1-transcription-factor-is-downregulated-in-acute-promyelocytic-leukemia
#8
Emiliano Fabiani, Giulia Falconi, Nélida Inés Noguera, Ernestina Saulle, Laura Cicconi, Mariadomenica Divona, Cristina Banella, Alessandra Picardi, Anna Maria Cerio, Letizia Boe, Massimo Sanchez, Elvira Pelosi, Ugo Testa, Francesco Lo-Coco, Maria Teresa Voso
Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136555/non-targeted-metabolomics-guided-sildenafil-metabolism-study-in-human-liver-microsomes
#9
Ju-Hyun Kim, Jun Hyun Jo, Kyung-Ah Seo, Hayoung Hwang, Hye Suk Lee, Sangkyu Lee
Metabolomics combined with high-resolution mass spectrometry (HR-MS) and multivariate data analysis has broad applications in the study of xenobiotic metabolism. Although information about xenobiotic metabolism is essential to understand toxic mechanisms, pharmacokinetic parameters and excretion pathways, it is limited to predict all generated metabolites in biological fluids. Here, we revisited sildenafil metabolism in human liver microsomes using a metabolomics approach to achieve a global picture of sildenafil phase 1 metabolism...
November 7, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29135282/genome-wide-dna-methylation-drives-human-embryonic-stem-cell-erythropoiesis-by-remodeling-gene-expression-dynamics
#10
Zhijing Liu, Qiang Feng, Pengpeng Sun, Yan Lu, Minlan Yang, Xiaowei Zhang, Xiangshu Jin, Yulin Li, Shi-Jiang Lu, Chengshi Quan
AIM: To investigate the role of DNA methylation during erythrocyte production by human embryonic stem cells (hESCs). METHODS: We employed an erythroid differentiation model from hESCs, and then tracked the genome-wide DNA methylation maps and gene expression patterns through an Infinium HumanMethylation450K BeadChip and an Ilumina Human HT-12 v4 Expression Beadchip, respectively. RESULTS: A negative correlation between DNA methylation and gene expression was substantially enriched during the later differentiation stage and was present in both the promoter and the gene body...
November 14, 2017: Epigenomics
https://www.readbyqxmd.com/read/29135280/factors-affecting-mouse-somatic-cell-nuclear-reprogramming-by-rabbit-ooplasms
#11
Xia Huang, Lili Song, Zhiyan Zhan, Haihui Gu, Haizhong Feng, Yanxin Li
Successful development of interspecies somatic cell nuclear transfer (iSCNT) embryos depends on compatibilities between ooplasmic and nuclear components. However, the mechanisms by which the compatibilities are regulated are still unknown. In this study, using mouse Oct4-green fluorescent protein (GFP) cells as donors and rabbit oocytes as recipients, we show that Oct4 and other pluripotency related genes were reactivated in some of mouse-rabbit iSCNT embryos, which could also activate Oct4 promoter-driven GFP reporter gene expression...
November 14, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/29133832/jmjd8-is-a-novel-endoplasmic-reticulum-protein-with-a-jmjc-domain
#12
Kok Siong Yeo, Ming Cheang Tan, Yat-Yuen Lim, Chee-Kwee Ea
Jumonji C (JmjC) domain-containing proteins have been shown to regulate cellular processes by hydroxylating or demethylating histone and non-histone targets. JMJD8 belongs to the JmjC domain-only family that was recently shown to be involved in angiogenesis and TNF-induced NF-κB signaling. Here, we employed bioinformatic analysis and immunofluorescence microscopy to examine the physiological properties of JMJD8. We demonstrated that JMJD8 localizes to the lumen of endoplasmic reticulum and that JMJD8 forms dimers or oligomers in vivo...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29131441/genetic-and-epigenetic-regulation-of-major-histocompatibility-complex-class-i-gene-expression-in-bovine-trophoblast-cells
#13
Bi Shi, Aaron J Thomas, Abby D Benninghoff, Benjamin R Sessions, Qinggang Meng, Parveen Parasar, Heloisa M Rutigliano, Kenneth L White, Christopher J Davies
PROBLEM: The regulatory mechanisms governing differential expression of classical major histocompatibility complex (MHC) class I (MHC-Ia) and non-classical MHC class I (MHC-Ib) genes are poorly understood. METHOD OF STUDY: Quantitative reverse transcription- polymerase chain reaction (PCR) was used to compare the abundance of MHC-I transcripts and related transcription factors in peripheral blood mononuclear cells (PBMC) and placental trophoblast cells (PTC). Methylation of MHC-I CpG islands was detected by bisulfite treatment and next-generation sequencing...
November 12, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29128601/isolation-modification-and-cytotoxic-evaluation-of-stilbenoids-from-acanthopanax-leucorrhizus
#14
Hao-Bin Hu, Hai-Peng Liang, Hai-Ming Li, Ru-Nan Yuan, Jiao Sun, La-La Zhang, Ming-Hu Han, Yun Wu
Twenty natural stilbenoids (1-20), including seven new stilbenoids (2, 4-7, 19, 20) and thirteen known stilbenoids (1, 3, 8-18), were isolated from the stem barks of Acanthopanax leucorrhizus, and six modified stilbenoid derivatives (1a, 2a, 4a, 4b, 7a and 17a) were obtained via methylation, demethylation and isopentenylation of the corresponding isolates (1, 2, 4, 7 and 17). These stilbenoids were structurally characterized by comprehensive analysis of their spectroscopic data and comparison with literature information, and evaluated for their cytotoxic activities against three human tumor cell lines (leukemia HL-60, hepatoma SMMC-7721 and breast carcinoma MCF-7) in vitro by MTT assay...
November 8, 2017: Fitoterapia
https://www.readbyqxmd.com/read/29128527/endogenously-generated-dna-nucleobase-modifications-source-and-significance-as-possible-biomarkers-of-malignant-transformation-risk-and-role-in-anticancer-therapy
#15
REVIEW
Ryszard Olinski, Daniel Gackowski, Marcus S Cooke
The DNA of all living cells undergoes continuous structural and chemical alteration, which may be derived from exogenous sources, or endogenous, metabolic pathways, such as cellular respiration, replication and DNA demethylation. It has been estimated that approximately 70,000 DNA lesions may be generated per day in a single cell, and this has been linked to a wide variety of diseases, including cancer. However, it is puzzling why potentially mutagenic DNA modifications, occurring at a similar level in different organs/tissue, may lead to organ/tissue specific cancers, or indeed non-malignant disease - what is the basis for this differential response? We suggest that it is perhaps the precise location of damage, within the genome, that is a key factor...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29127936/synthesis-of-n-3-4-11-c-methylpiperazin-1-yl-1-5-methylpyridin-2-yl-1h-pyrazol-5-yl-pyrazolo-1-5-a-pyrimidine-3-carboxamide-as-a-new-potential-pet-agent-for-imaging-of-irak4-enzyme-in-neuroinflammation
#16
Xiaohong Wang, Wenzhi Xu, Caihong Miao, Fugui Dong, Wei Li, Min Wang, Mingzhang Gao, Qi-Huang Zheng, Zhidong Xu
The reference standard N-(3-(4-methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)-3-(piperazin-1-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[(11)C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([(11)C]9) was prepared from its precursor with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with SPE in 50-60% radiochemical yield, based on [(11)C]CO2 and decay corrected to EOB...
November 6, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/29126272/generation-of-alloantigen-specific-induced-treg-stabilized-by-vitamin-c-treatment-and-its-application-for-prevention-of-acute-graft-versus-host-disease-model
#17
Hidenori Kasahara, Taisuke Kondo, Hiroko Nakatsukasa, Shunsuke Chikuma, Minako Ito, Makoto Ando, Yutaka Kurebayashi, Takashi Sekiya, Taketo Yamada, Shinichiro Okamoto, Akihiko Yoshimura
Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation, and graft-versus-host disease (GVHD) in hematopoietic stem-cell transplantation. Although in vitro-expanded antigen-specific induced Tregs (iTregs) have been considered to be a promising therapeutic agent against such excessive immune reactions, the instability of iTregs after transfer is a fundamental problem in their clinical application...
November 4, 2017: International Immunology
https://www.readbyqxmd.com/read/29124976/rethinking-mercury-the-role-of-selenium-in-the-pathophysiology-of-mercury-toxicity
#18
Henry A Spiller
INTRODUCTION: There is increasing evidence that the pathophysiological target of mercury is in fact selenium, rather than the covalent binding of mercury to sulfur in the body's ubiquitous sulfhydryl groups. The role of selenium in mercury poisoning is multifaceted, bidirectional, and central to understanding the target organ toxicity of mercury. METHODS: An initial search was performed using Medline/PubMed, Toxline, Google Scholar, and Google for published work on mercury and selenium...
November 10, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/29124283/semi-rational-engineering-of-cyp153a35-to-enhance-%C3%AF-hydroxylation-activity-toward-palmitic-acid
#19
Eunok Jung, Beom Gi Park, Hee-Wang Yoo, Joonwon Kim, Kwon-Young Choi, Byung-Gee Kim
CYP153A35 from Gordonia alkanivorans was recently characterized as fatty acid ω-hydroxylase. To enhance the catalytic activity of CYP153A35 toward palmitic acid, site-directed saturation mutagenesis was attempted using a semi-rational approach that combined structure-based computational analysis and subsequent saturation mutagenesis. Using colorimetric high-throughput screening (HTS) method based on O-demethylation activity of P450, CYP153A35 D131S and D131F mutants were selected. The best mutant, D131S, having a single mutation on BC-loop, showed 13- and 17-fold improvement in total turnover number (TTN) and catalytic efficiency (k cat/K M) toward palmitic acid compared to wild-type, respectively...
November 9, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29120380/in-vitro-phase-i-metabolism-of-crv431-a-novel-oral-drug-candidate-for-chronic-hepatitis-b
#20
Daniel J Trepanier, Daren R Ure, Robert T Foster
The cytochrome P450-mediated Phase I in vitro metabolism of CRV431 was studied using selective chemical inhibition and recombinant human enzymes. Additionally, the metabolic profile of CRV431 in human, rat, and monkey liver microsomes was investigated. Liver microsomes were incubated for 0-80 min with CRV431, and the metabolite profile was assessed by electrospray ionization liquid chromatography mass spectrometry (ESI-LCMS). CRV431 was extensively metabolized through oxidation to produce various hydroxylated and demethylated species...
November 9, 2017: Pharmaceutics
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