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Mei Mei, Haojun Song, Lina Chen, Bin Hu, Ru Bai, Diandou Xu, Ying Liu, Yuliang Zhao, Chunying Chen
BACKGROUND: Epidemiological studies have suggested that elevated levels of air pollution contribute to an increased incidence or severity of asthma. Although late-onset adult asthma seems to be more attributable to environmental risk factors, limited data is available on the impact of early-life exposure to size-fractionated ambient particulate matter (PM) on asthma in adults. We aimed to determine the effect on the development and exacerbation of asthma in the adult after the mice were exposed as juveniles to three size-fractionated ambient particulates collected from Beijing...
March 14, 2018: Particle and Fibre Toxicology
Mostafa Moradi Sarabi, Fakhraddin Naghibalhossaini
Growing evidence suggests a role of polyunsaturated fatty acids (PUFA) in the prevention of various types of malignancy, including colorectal cancer (CRC). No published studies have yet examined the direct effect of PUFA treatment on DNA methylation in CRC cells. In this study, 5 human CRC cells were treated with 100 μM DHA, EPA, and LA for 6 days and changes in their global- and gene-specific DNA methylation status as well as expression of DNA methyl transferases (DNMT) were investigated. Cell-type specific differences in DNA methylation and expression of DNMTs were observed in PUFA-treated cells...
February 22, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yi Fang, Shoulong Deng, Jinlong Zhang, Haijun Liu, Yihai Li, Xiaosheng Zhang, Yixun Liu
Cumulus cells of pre-pubertal domestic animals are dysfunctional, perhaps due to age-specific epigenetic events. This study was designed to determine effects of melatonin treatment of donors on methylation modification of pre-pubertal cumulus cells. Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) were collected from eighteen lambs which were randomly divided into control group (C) and melatonin group given an 18 mg melatonin implant subcutaneous (M). Compared to the C group, the M group had higher concentrations of melatonin in plasma and follicular fluid ( p < 0...
February 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yuning Sun, Rongfeng Xu, Jia Huang, Yuyu Yao, Xiaodong Pan, Zhongpu Chen, Genshan Ma
BACKGROUND: C-kit-positive cardiac stem cells (CSCs) have been shown to be a promising candidate treatment for myocardial infarction and heart failure. Insulin-like growth factor (IGF)-1 is an anabolic growth hormone that regulates cellular proliferation, differentiation, senescence, and death in various tissues. Although IGF-1 promotes the migration and proliferation of c-kit-positive mouse CSCs, the underlying mechanism remains unclear. METHODS: Cells were isolated from adult mouse hearts, and c-kit-positive CSCs were separated using magnetic beads...
February 21, 2018: Stem Cell Research & Therapy
Feng Li, Chen-Yang Qiao, Shuai Gao, Yu-Chen Fan, Long-Yan Chen, Kai Wang
BACKGROUND AND AIM: The initiation and progression of hepatocellular carcinoma (HCC) is a multistage process involving a variety of changes at the gene level. Insulin-like growth factor binding protein 7 (IGFBP7) methylation plays a crucial role in HCC development. The main purpose of this study was to investigate the relationship between oxidative stress, DNA methyltransferases (DNMTs) expression and IGFBP7 methylation, and to evaluate the prognostic value of serum IGFBP7 methylation status in patients with HCC after hepatectomy...
February 20, 2018: Free Radical Research
Silvana Rošić, Rachel Amouroux, Cristina E Requena, Ana Gomes, Max Emperle, Toni Beltran, Jayant K Rane, Sarah Linnett, Murray E Selkirk, Philipp H Schiffer, Allison J Bancroft, Richard K Grencis, Albert Jeltsch, Petra Hajkova, Peter Sarkies
Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark in eukaryotes. Once introduced, 5meC can be maintained through DNA replication by the activity of 'maintenance' DNA methyltransferases (DNMTs). Despite their ancient origin, DNA methylation pathways differ widely across animals, such that 5meC is either confined to transcribed genes or lost altogether in several lineages. We used comparative epigenomics to investigate the evolution of DNA methylation. Although the model nematode Caenorhabditis elegans lacks DNA methylation, more basal nematodes retain cytosine DNA methylation, which is targeted to repeat loci...
February 19, 2018: Nature Genetics
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
Eric Hervouet, Paul Peixoto, Régis Delage-Mourroux, Michaël Boyer-Guittaut, Pierre-François Cartron
Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes...
2018: Clinical Epigenetics
Shengjun Ji, Xin Ding, Jiang Ji, Haohao Wu, Rui Sun, Xiaoyang Li, Liyuan Zhang, Ye Tian
Impairment of neurogenesis in the hippocampus following whole-brain irradiation is the most important mechanism of radiation-induced cognitive dysfunction. However, the underlying mechanism remains obscure, meaning an ideal therapeutic target has not been identified. Evidence indicates that DNA methylation in neurons regulates synaptic plasticity and neuronal network activity. In the present study, the expression of DNA methyltransferases (DNMTs) in the hippocampus was analyzed to investigate their potential function in radiation-induced neurogenesis impairment...
March 2018: Oncology Letters
Yun Zhang, Sebastian Pötter, Chih-Wei Chen, Ruifang Liang, Kolja Gelse, Ingo Ludolph, Raymund E Horch, Oliver Distler, Georg Schett, Jörg H W Distler, Clara Dees
OBJECTIVES: The enzyme poly(ADP-ribose) polymerase-1 (PARP-1) transfers negatively charged ADP-ribose units to target proteins. This modification can have pronounced regulatory effects on target proteins. Recent studies showed that PARP-1 can poly(ADP-ribosyl)ate (PARylate) Smad proteins. However, the role of PARP-1 in the pathogenesis of systemic sclerosis (SSc) has not been investigated. METHODS: The expression of PARP-1 was determined by quantitative PCR and immunohistochemistry...
February 3, 2018: Annals of the Rheumatic Diseases
Francesco Guarasci, Patrizia D'Aquila, Maurizio Mandalà, Sabrina Garasto, F Lattanzio, Andrea Corsonello, Giuseppe Passarino, Dina Bellizzi
A number of epigenetic studies have demonstrated that DNA methylation patterns exhibit a tissue specificity, but not much has been done to highlight the extent of this phenomenon. Moreover, it is unknown how external factors modulate the plasticity of the tissue specific epigenetic profile. We examined global DNA methylation profiles in tissues from rats of different age, fed with standard or low-calorie diet, and evaluated their association with aging and nutrition. Tissue-specific variations occur during aging with hyper-methylation taking place in all tissues except for liver...
February 7, 2018: Mechanisms of Ageing and Development
Min Ma, Qiong-Jie Zhou, Yu Xiong, Bin Li, Xiao-Tian Li
Previous studies have demonstrated a dynamic epigenetic regulation of genes expression in placenta trophoblasts and a dynamic imbalance of DNA methylation and hydroxymethylation. Reduced IGF-1 has been observed in preeclampsia. This study was to investigate the interactive roles between IGF-1 and the global DNA methylation/hydroxymethylation, and the status of DNA methylation/hydroxymethylation and associated enzymes such as DNMTs and TETs in peeeclamptic placentas and hypoxic trophoblasts. It was found that IGF-1 was decreased in preeclamptic placentas and hypoxic trophoblasts when compared to the control group using immunohistochemisty, western blot, qRT-PCR and ELISA...
2018: American Journal of Translational Research
Yui-Ping Weng, Pin-Feng Hung, Wen-Yen Ku, Chang-Yuan Chang, Bo-Han Wu, Ming-Han Wu, Jau-Ying Yao, Ji-Rui Yang, Chia-Huei Lee
Epigenome aberrations have been observed in tobacco-associated human malignancies. (-)-epigallocatechin-3-gallate (EGCG) has been proven to modulate gene expression by targeting DNA methyltransferases (DNMTs) through a proposed mechanism involving the gallate moiety of EGCG. We show that gallic acid (GA) changes the methylome of lung cancer and pre-malignant oral cell lines and markedly reduces both nuclear and cytoplasmic DNMT1 and DNMT3B within 1 week. GA exhibits stronger cytotoxicity against the lung cancer cell line H1299 than EGCG...
January 2, 2018: Oncotarget
Rafael Sebastián Fort, Cecilia Mathó, Murilo Vieira Geraldo, María Carolina Ottati, Alex Shimura Yamashita, Kelly Cristina Saito, Katia Ramos Moreira Leite, Manuel Méndez, Noemí Maedo, Laura Méndez, Beatriz Garat, Edna Teruko Kimura, José Roberto Sotelo-Silveira, María Ana Duhagon
BACKGROUND: Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer...
February 2, 2018: BMC Cancer
Wei Zhang, Shanshan Zhou, Yuwei Gao, Hongquan Song, Xiaohui Jiao, Xiaotong Wang, Yong Li
Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces cleft palate formation in mice. This TCDD treatment, which may be considered an environmental factor in cleft palate formation, is associated with alterations in DNA methylation. However, the underlying molecular mechanisms of DNA methylation produced by TCDD in mouse embryos are poorly understood. DNA methyltransferases (DNMTs) and methyl‑CpG binding domain proteins (MBDs) are thought to be closely associated with the actions of DNA methylation...
January 30, 2018: Molecular Medicine Reports
Kousuke Sato, Yuma Kunitomo, Yukiko Kasai, Shohei Utsumi, Isao Suetake, Shoji Tajima, Satoshi Ichikawa, Akira Matsuda
In chromatin, 5-methylcytosine (mC), which represents the 5th nucleobase in genomic DNA, plays a role as an inducer of epigenetic changes. Tumor cells exhibit aberrant DNA methylation patterns, and inhibition of human DNA cytosine-5 methyltransferase (DNMT), which is responsible for generating mC in CpG sequences, is an effective strategy to treat various cancers. Here, we describe the design, synthesis, and evaluation of the properties of 2-amino-4-halopyridine-C-nucleosides (dXP) and oligodeoxyribonucleotides (ODNs) containing dXP as a novel mechanism-based inhibitor of DNMTs...
February 2, 2018: Chembiochem: a European Journal of Chemical Biology
Yi-Dong Hong, Jian Zhang, Ming Zhuang, Wei Li, Puy-Uan Wu, Ru-Tian Li, Nan Hu, Bao-Xiang Bian, Zi-Yan Song, Feng-Lei Wu
Hypermethylation of the transcription factor AP-2 epsilon (TFAP2E) gene affects 5-fluorouridine (5-FU) resistance in gastric cancer (GC) patients. The epigenetic inhibitor 5-Aza-2'-deoxycytidine (DAC), which reverses DNA methylation by targeting DNA methyltransferases (DNMTs), has potential to sensitize GC to 5-FU. Nevertheless, DNA demethylation only DAC transiently occurs since DAC is unstable in aqueous solutions, which limits its potential. Here we developed intelligent nanoparticles (NPs) comprising gelatinase with polyethylene glycol (PEG) and poly-ε-caprolactone) (PCL) to specifically deliver DAC (DAC-TNPs) to tumors...
December 29, 2017: Oncotarget
Souichiro Nakamae, Yukiko Toba, Kazuo Takayama, Fuminori Sakurai, Hiroyuki Mizuguchi
Human induced pluripotent stem cell-derived hepatocyte-like cells (HLCs) are expected to be utilized in pharmaceutical research, including drug screening. However, the hepatocyte functions of the HLCs are still lower than those of human hepatocytes. Therefore, we attempted to improve the hepatocyte differentiation method by modulating the DNA epigenetic status. We first examined the expression profiles of the maintenance DNA methyltransferase (DNMT) 1 and the de novo DNMTs DNMT3A and DNMT3B, all of which are essential for mammalian development...
February 27, 2018: Stem Cells and Development
Zheng Peng, Wenjun Zhou, Chun Zhang, Huining Liu, Yi Zhang
BACKGROUND Cancer stem cells (CSCs), in choriocarcinoma and other carcinomas, possess the ability of self-renewal and multilineage differentiation potential. We previous isolated choriocarcinoma cancer stem-like cells (CSLCs), which hold the stemness characteristics of CSCs. Epigenetic modifications have emerged as drivers in tumorigenesis, but the mechanisms of CSCs are largely unknown, and new drug therapies are needed to break the persistence of CSCs. MATERIAL AND METHODS Quantitative real-time PCR (qRT-PCR) and Western blot analysis were performed to detect the expression of DNMTs, HDACs, and stemness-genes...
January 24, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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