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https://www.readbyqxmd.com/read/28229968/cytotoxic-and-toxicogenomic-effects-of-silibinin-in-bladder-cancer-cells-with-different-tp53-status
#1
Daiane Teixeira DE Oliveira, Andre Luiz Ventura Savio, Joao Paulo DE Castro Marcondes, Tatiane Martins Barros, Ludmila Correia Barbosa, Daisy Maria Favero Salvadori, Glenda Nicioli DA Silva
Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229923/epigenetic-regulation-of-reln-and-gad1-in-the-frontal-cortex-fc-of-autism-spectrum-disorder-asd-subjects
#2
Adrian Zhubi, Ying Chen, Alessandro Guidotti, Dennis R Grayson
Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain...
February 13, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28222718/abnormal-epigenetic-changes-during-differentiation-of-human-skeletal-muscle-stem-cells-from-obese-subjects
#3
Cajsa Davegårdh, Christa Broholm, Alexander Perfilyev, Tora Henriksen, Sonia García-Calzón, Lone Peijs, Ninna Schiøler Hansen, Petr Volkov, Rasmus Kjøbsted, Jørgen F P Wojtaszewski, Maria Pedersen, Bente Klarlund Pedersen, Dov B Ballak, Charles A Dinarello, Bas Heinhuis, Leo A B Joosten, Emma Nilsson, Allan Vaag, Camilla Scheele, Charlotte Ling
BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals...
February 22, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28222434/a-feedback-loop-between-mir-30a-c-5p-and-dnmt1-mediates-cisplatin-resistance-in-ovarian-cancer-cells
#4
Xi Han, Shuai Zhen, Zhongxue Ye, Jiaojiao Lu, Lijie Wang, Pan Li, Jie Li, Xia Zheng, Huijin Li, Wei Chen, Le Zhao, Xu Li
BACKGROUND: Many microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression patterns have been suggested to correlate with chemo-resistance of cancer cells. We aim to study the role of miR-30 family members in cisplatin-resistance of ovarian cancer cells. METHODS: qRT-PCR was used to compare differential expression levels of miR-30 family members in ovarian cancer cell line A2780 and its cisplatin-resistant derivative CP70. Changes of cisplatin-sensitivity in miR-30a-5p- and miR-30c-5p-overexpressed-CP70 cells and miR-30a-5p- and miR-30c-5p-inhibited-A2780 cells were examined by CCK8 assay and apoptosis analysis using flow cytometry; targets of miR-30a/c-5p were analyzed by western blotting and luciferase reporter assay; methylation regulation of pre-miR-30a/c-5p was examined by methylation specific PCR...
February 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28215845/converting-adult-pancreatic-islet-%C3%AE-cells-into-%C3%AE-cells-by-targeting-both-dnmt1-and-arx
#5
Harini Chakravarthy, Xueying Gu, Martin Enge, Xiaoqing Dai, Yong Wang, Nicolas Damond, Carolina Downie, Kathy Liu, Jing Wang, Yuan Xing, Simona Chera, Fabrizio Thorel, Stephen Quake, Jose Oberholzer, Patrick E MacDonald, Pedro L Herrera, Seung K Kim
Insulin-producing pancreatic β cells in mice can slowly regenerate from glucagon-producing α cells in settings like β cell loss, but the basis of this conversion is unknown. Moreover, it remains unclear if this intra-islet cell conversion is relevant to diseases like type 1 diabetes (T1D). We show that the α cell regulators Aristaless-related homeobox (Arx) and DNA methyltransferase 1 (Dnmt1) maintain α cell identity in mice. Within 3 months of Dnmt1 and Arx loss, lineage tracing and single-cell RNA sequencing revealed extensive α cell conversion into progeny resembling native β cells...
February 12, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28203606/dna-methylation-in-oligodendroglial-cells-during-developmental-myelination-and-in-disease
#6
Sarah Moyon, Patrizia Casaccia
Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28196140/hypoxia-inducible-factors-regulate-the-transcription-of-the-sprouty2-gene-and-expression-of-the-sprouty2-protein
#7
Xianlong Gao, Kristin C Hicks, Paul Neumann, Tarun B Patel
Receptor Tyrosine Kinase (RTK) signaling plays a major role in tumorigenesis and normal development. Sprouty2 (Spry2) attenuates RTK signaling and inhibits processes such as angiogenesis, cell proliferation, migration and survival, which are all upregulated in tumors. Indeed in cancers of the liver, lung, prostate and breast, Spry2 protein levels are markedly decreased correlating with poor patient prognosis and shorter survival. Thus, it is important to understand how expression of Spry2 is regulated. While prior studies have focused on the post-translation regulation of Spry2, very few studies have focused on the transcriptional regulation of SPRY2 gene...
2017: PloS One
https://www.readbyqxmd.com/read/28192769/disorganization-at-the-stage-of-schizophrenia-clinical-outcome-clinical-biological-study
#8
A Nestsiarovich, V Obyedkov, H Kandratsenka, M Siniauskaya, I Goloenko, N Waszkiewicz
BACKGROUND: According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. METHODS: We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality...
December 30, 2016: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28191262/maternal-intake-of-methyl-group-donors-affects-dna-methylation-of-metabolic-genes-in-infants
#9
Sara Pauwels, Manosij Ghosh, Radu Corneliu Duca, Bram Bekaert, Kathleen Freson, Inge Huybrechts, Sabine A S Langie, Gudrun Koppen, Roland Devlieger, Lode Godderis
BACKGROUND: Maternal nutrition during pregnancy and infant nutrition in the early postnatal period (lactation) are critically involved in the development and health of the newborn infant. The Maternal Nutrition and Offspring's Epigenome (MANOE) study was set up to assess the effect of maternal methyl-group donor intake (choline, betaine, folate, methionine) on infant DNA methylation. Maternal intake of dietary methyl-group donors was assessed using a food-frequency questionnaire (FFQ)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28182000/knockdown-of-long-non-coding-rna-hotair-increases-mir-454-3p-by-targeting-stat3-and-atg12-to-inhibit-chondrosarcoma-growth
#10
Xing Bao, Tingting Ren, Yi Huang, Kunkun Sun, Shidong Wang, Kuisheng Liu, Bingxin Zheng, Wei Guo
Current practices for the therapy of chondrosarcoma, including wide-margin surgical resection and chemotherapy, are less than satisfactory. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) have an essential role in the initiation and progression of tumors. As a typical lncRNA, HOTAIR is significantly overexpressed in various tumors. However, the function and potential biological mechanisms of HOTAIR in human chondrosarcoma remain unknown. Quantitative RT-PCR demonstrated that HOTAIR expression was upregulated in chondrosarcoma tissues and cell lines...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28177910/fqi1-a-transcription-methylation-switch-for-cancer
#11
EDITORIAL
Olga A Guryanova, Jonathan D Licht
News on: Transcription factor LSF-DNMT1 complex dissociation by FQI1 leads to aberrant DNA methylation and gene expression byHang Gyeong Chin, et al. Oncotarget. 2016; 7(50):83627-83640. doi: 10.18632/oncotarget.13271.
February 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177119/downregulation-of-methyltransferase-dnmt2-results-in-condition-dependent-telomere-shortening-and-senescence-or-apoptosis-in-mouse-fibroblasts
#12
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Maciej Wnuk
Dnmt2 is a highly conserved methyltransferase of uncertain biological function(s). As Dnmt2 was considered as a driver of fruit fly longevity and a modulator of stress response, we decided to evaluate the role of Dnmt2 during stress-induced premature senescence in NIH3T3 mouse fibroblasts. Stable knockdown of Dnmt2 resulted in hydrogen peroxide-mediated sensitivity and apoptosis, whereas in the control conditions, senescence was induced. Cellular senescence was accompanied by elevated levels of p53 and p21, decreased telomere length and telomerase activity, increased production of reactive oxygen species and protein carbonylation, and DNA damage...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28167789/dnmt3a-restrains-mast-cell-inflammatory-responses
#13
Cristina Leoni, Sara Montagner, Andrea Rinaldi, Francesco Bertoni, Sara Polletti, Chiara Balestrieri, Silvia Monticelli
DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in DNMT3A correlate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to acute and chronic stimuli, both in vitro and in vivo...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28161254/pharmacological-inhibition-of-dna-methyltransferase-1-promotes-neuronal-differentiation-from-rodent-and-human-nasal-olfactory-stem-progenitor-cell-cultures
#14
I Franco, L Ortiz-López, B Roque-Ramírez, G B Ramírez-Rodríguez, M Lamas
Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that include DNA-methylation and other chromatin modifications that could be experimentally manipulated in order to increase neuronal differentiation. The aim of the present study was the characterization of primary cultures and consecutive passages (P2-P10) of NOS/PCs isolated from male Swiss-Webster (mNOS/PCs) or healthy humans (hNOS/PCs)...
February 1, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28161170/maternal-supplementation-with-rumen-protected-methionine-increases-prepartal-plasma-methionine-concentration-and-alters-hepatic-mrna-abundance-of-1-carbon-methionine-and-transsulfuration-pathways-in-neonatal-holstein-calves
#15
C B Jacometo, Z Zhou, D Luchini, M N Corrêa, J J Loor
An important mechanism of nutritional "programming" induced by supplementation with methyl donors during pregnancy is the alteration of mRNA abundance in the offspring. We investigated the effects of rumen-protected Met (RPM) on abundance of 17 genes in the 1-carbon, Met, and transsulfuration pathways in calf liver from cows fed the same basal diet without (control, CON) or with RPM at 0.08% of diet dry matter/d (MET) from -21 through +30 d around calving. Biopsies (n = 8 calves per diet) were harvested on d 4, 14, 28, and 50 of age...
February 1, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28160561/an-association-between-overexpression-of-dna-methyltransferase-3b4-and-clear-cell-renal-cell-carcinoma
#16
You Liu, Liantao Sun, Peter Fong, Jie Yang, Zhuxia Zhang, Shuihui Yin, Shuyuan Jiang, Xiaolei Liu, Hongge Ju, Lihua Huang, Jing Bai, Kerui Gong, Shaochun Yan, Chunyang Zhang, Guo Shao
It is well known that abnormal DNA methylations occur frequently in kidney cancer. However, it remains unclear exactly which types of DNA methyltransferases (DNMT) contribute to the pathologies of kidney cancers. In order to determine the functions of DNA methyltransferase in kidney tumorigenesis on the molecular level, we examined the mRNA expression levels of DNMT1, DNMT3A, DNMT3B, and DNMT3B variants in renal cell carcinoma tissue. Both mRNA and protein levels of DNMT3B4, a splice variant of DNMT3B, were increased in renal cell carcinoma tissue compared with adjacent control tissues...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159994/missing-in-metastasis-b-regulated-by-dnmt1-functions-as-a-putative-cancer-suppressor-in-human-lung-giant-cell-carcinoma
#17
Hong Wang, Xiaomin Yu, Xiaofang Wang, Xiaokun Li, Shulin Yang
No abstract text is available yet for this article.
February 4, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28150521/drug-repurposing-and-therapeutic-anti-microrna-predictions-for-inhibition-of-oxidized-low-density-lipoprotein-induced-vascular-smooth-muscle-cell-associated-diseases
#18
Shun-Tsung Chen, Chien-Hung Huang, Victor C Kok, Chi-Ying F Huang, Jin-Shuei Ciou, Jeffrey J P Tsai, Nilubon Kurubanjerdjit, Ka-Lok Ng
Drug repurposing is a new method for disease treatments, which accelerates the identification of new uses for existing drugs with minimal side effects for patients. MicroRNA-based therapeutics are a class of drugs that have been used in gene therapy following the FDA's approval of the first anti-sense therapy. This study examines the effects of oxLDL on vascular smooth muscle cells (VSMCs) and identifies potential drugs and antimiRs for treating VSMC-associated diseases. The Connectivity Map (cMap) database is utilized to identify potential new uses of existing drugs...
December 22, 2016: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#19
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28143949/allelic-drop-out-during-polymerase-chain-reaction-due-to-g-quadruplex-structures-and-dna-methylation-is-widespread-at-imprinted-human-loci
#20
Aaron J Stevens, Millie G Taylor, F Grant Pearce, Martin A Kennedy
Loss of one allele during polymerase chain reaction (PCR) amplification of DNA, known as allelic drop-out, can be caused by a variety of mechanisms. Allelic drop-out during PCR may have profound implications for molecular diagnostic and research procedures that depend on PCR and assume biallelic amplification has occurred. Complete allelic drop-out due to the combined effects of cytosine methylation and G-quadruplex formation was previously described for a differentially methylated region of the human imprinted gene, MEST We now demonstrate that this parent-of-origin specific allelic drop-out can potentially occur at several other genomic regions that display genomic imprinting and have propensity for G-quadruplex formation, including AIM1, BLCAP, DNMT1, PLAGL1, KCNQ1 and GRB10 These findings demonstrate that systematic allelic drop-out during PCR is a general phenomenon for regions of the genome where differential allelic methylation and G-quadruplex motifs coincide, and suggest that great care must be taken to ensure biallelic amplification is occurring in such situations...
January 30, 2017: G3: Genes—Genomes—Genetics
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