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H-S Zhang, X-Y Ke, L-L Hu, J Wang, L-S Gao, J Xie
OBJECTIVE: We aimed to study changes and possible roles of epigenetic modification of candidate genes in the pathogenesis of bipolar disorder, and provide the basis for clinical diagnosis and analysis. PATIENTS AND METHODS: A total of 150 patients with bipolar disorder were enrolled in this study from January 2014 to June 2015; also, 50 healthy subjects were enrolled as control group. The patients were followed up for 18 months and followed up once every 3 months to review the methylation status...
March 2018: European Review for Medical and Pharmacological Sciences
Jiawei Xu, Teng Wang, Zhiyang Su, Xinyao Zhou, Yuqian Xiang, Lin He, Candong Li, Zhaoyang Yang, Xinzhi Zhao
The μ-opioid receptor (OPRM1) plays an important role in opiate addiction. The OPRM1 gene promoter showed hypermethylation in lymphocytes of opiate addicts as well as opioid medications users, while the methylation status displayed ethnic diversity. The purpose of the study was to investigate the methylation pattern of OPRM1 promoter in the Han Chinese population. We analyzed 22 CpG sites located in OPRM1 promoter in 186 former opiate addicts (94 males and 92 females) and 184 healthy controls (102 males and 82 females)...
March 21, 2018: Biochemical Genetics
Giulia F Del Gobbo, E Magda Price, Courtney W Hanna, Wendy P Robinson
Background: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in one-carbon metabolism that ensures the availability of methyl groups for methylation reactions. Two single-nucleotide polymorphisms (SNPs) in the MTHFR gene, 677C>T and 1298A>C, result in a thermolabile enzyme with reduced function. These variants, in both the maternal and/or fetal genes, have been associated with pregnancy complications including miscarriage, neural tube defects (NTDs), and preeclampsia (PE), perhaps due to altered capacity for DNA methylation (DNAm)...
2018: Clinical Epigenetics
Jacob Rozmus, Sabine Ivison, Amina Kariminia, Vivian M Leung, Susanna Sung, Peter Subrt, Stephanie J Lee, Eric Boilard, Irwin Walker, Ronan Foley, Jeff Lipton, Geneviève Gallagher, Stephen Couban, Kirk R Schultz
Toll-like receptor-9 (TLR9) responsive B cells have previously been associated with the onset of extensive chronic graft-versus-host disease (cGvHD). We hypothesized that the onset of cGvHD associated with a higher level of plasma-free mitochondrial DNA (mtDNA), a putative TLR9 agonist. Plasma cell-free mtDNA levels were measured in 39 adult patients post-HSCT with and without cGvHD. mtDNA was isolated from plasma and quantified by Q-PCR amplification. We correlated B cell responsiveness to CpG-DNA, a prototypical TLR9 agonist, and previously identified cGVHD biomarkers with mtDNA levels...
March 21, 2018: Bone Marrow Transplantation
Kristine Hardy, Corey Smith, Wen Juan Tu, Robert McCuaig, Archana Panikkar, Vijayendra Dasari, Fan Wu, Siok-Keen Tey, Geoffrey R Hill, Rajiv Khanna, Sudha Rao
Immune reconstitution following hematopoietic stem cell transplantation (HSCT) is critical in preventing harmful sequelae in recipients with cytomegalovirus (CMV) infection. To understand the molecular mechanisms underlying immune reconstitution kinetics, we profiled the transcriptome-chromatin accessibility landscape of CMV-specific CD8+ T cells from HCST recipients with different immune reconstitution efficiencies. CMV-specific T cells from HSCT recipients with stable antiviral immunity expressed higher levels of interferon/defense response and cell cycle genes in an interconnected network involving PI3KCG , STAT5B , NFAT , RBPJ , and lower HDAC6 , increasing chromatin accessibility at the enhancer regions of immune and T-cell receptor signaling pathway genes...
March 27, 2018: Blood Advances
Moslem Ahmadi, Fateme Sadri-Ardalani, Mohammad M Amiri, Mahmood Jeddi-Tehrani, Mahdi Shabani, Fazel Shokri
AIM: We investigated cellular and protective immune responses in mice vaccinated with recombinant HER2 extracellular subdomains. MATERIALS & METHODS: Balb/C mice were immunized with recombinant full HER2 extracellular domain and subdomain proteins. Humoral and cellular immune response and antitumor effect was evaluated using a syngeneic mice tumor model. RESULTS: All recombinant proteins induced secretion of IL-4 and particularly IFN-γ and IL-17 cytokines...
March 1, 2018: Immunotherapy
Yanting Luo, Jianlin He, Xiguang Xu, Ming-An Sun, Xiaowei Wu, Xuemei Lu, Hehuang Xie
Embryonic stem cells (ESCs) consist of a population of self-renewing cells displaying extensive phenotypic and functional heterogeneity. Research towards the understanding of the epigenetic mechanisms underlying the heterogeneity among ESCs is still in its initial stage. Key issues, such as how to identify cell-subset specifically methylated loci and how to interpret the biological meanings of methylation variations remain largely unexplored. To fill in the research gap, we implemented a computational pipeline to analyze single-cell methylome and to perform an integrative analysis with single-cell transcriptome data...
March 2018: PLoS Computational Biology
Yuet-Kin Leung, Bin Ouyang, Liang Niu, Changchun Xie, Jun Ying, Mario Medvedovic, Aimin Chen, Pal Weihe, Damaskini Valvi, Philippe Grandjean, Shuk-Mei Ho
Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from chemical exposures. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood...
March 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Jarunya Samsuwan, Tachapol Muangsub, Pattamawadee Yanatatsaneejit, Apiwat Mutirangura, Nakarin Kitkumthorn
According to the tissue-specific methylation database (doi: 10.1016/j.gene.2014.09.060), methylation at CpG locus cg03096975 in EML2 has been preliminarily proven to be specific to brain tissue. In this study, we enlarged sample size and developed a technique for identifying brain tissue in aged samples. Combined Bisulfite Restriction Analysis-for EML2 (COBRA-EML2) technique was established and validated in various organ samples obtained from 108 autopsies. In addition, this technique was also tested for its reliability, minimal DNA concentration detected, and use in aged samples and in samples obtained from specific brain compartments and spinal cord...
March 9, 2018: Forensic Science International
Jing Jie, Yixin Zhang, Hongyue Zhou, Xiaoyu Zhai, Nannan Zhang, Hongyan Yuan, Weihua Ni, Guixiang Tai
Mucin 1 ( MUC1 ), being an oncogene, is an attractive target in tumor immunotherapy. Maltose binding protein (MBP) is a potent built-in adjuvant to enhance protein immunogenicity. Thus, a recombinant MUC1 and MBP antitumor vaccine (M-M) was constructed in our laboratory. To enhance the antitumor immune activity of M-M, CpG oligodeoxynucleotides 1826 (CpG 1826), a toll-like receptor-9 agonist, was examined in this study as an adjuvant. The combination of M-M and CpG 1826 significantly inhibited MUC1 -expressing B16 cell growth and prolonged the survival of tumor-bearing mice...
March 20, 2018: International Journal of Molecular Sciences
Chunhui Lai, Siliang Duan, Fang Ye, Xiaoqiong Hou, Xi Li, Jin Zhao, Xia Yu, Zixi Hu, Zhuoran Tang, Fengzhen Mo, Xiaomei Yang, Xiaoling Lu
PURPOSE: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. METHODS: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine...
2018: Theranostics
Andrew D Kelly, Jozef Madzo, Priyanka Madireddi, Patricia Kropf, Charly R Good, Jaroslav Jelinek, Jean-Pierre J Issa
Acute myeloid leukemia (AML) often harbors mutations in epigenetic regulators, and also has frequent DNA hypermethylation, including the presence of CpG island methylator phenotypes (CIMPs). Although global hypomethylation is well known in cancer, the question of whether distinct demethylator phenotypes (DMPs) exist remains unanswered. Using Illumina 450k arrays for 194 patients from The Cancer Genome Atlas, we identified two distinct DMPs by hierarchical clustering: DMP.1 and DMP.2. DMP.1 cases harbored mutations in NPM1 (94%), FLT3 (71%) and DNMT3A (61%)...
March 7, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Sandra Vreman, Gael Auray, Huub F J Savelkoul, Annemarie Rebel, Artur Summerfield, Norbert Stockhofe-Zurwieden
The present study investigated the innate immune response in vitro to determine porcine neonate responses with Toll-like receptor (TLR)2 ligand (Pam3Cys) or TLR9 ligand (CpG) and compare these with adults. We identified the same phenotypically defined dendritic cells (DC) subsets and DC proportions in porcine neonate and adult blood by flow cytometry, which were plasmacytoid DCs (pDCs): CD14- CD4+ CD172a+ CADM1- ) and conventional DCs (cDCs), the latter being further divided into a cDC1 (CD14- CD4- CD172alow CADM1+ ) and a cDC2 (CD14- CD4- CD172a+ CADM1+ ) subset...
March 16, 2018: Developmental and Comparative Immunology
Maria Giulia Bacalini, Claudio Franceschi, Davide Gentilini, Francesco Ravaioli, Xiaoyuan Zhou, Daniel Remondini, Chiara Pirazzini, Cristina Giuliani, Elena Marasco, Noémie Gensous, Anna Maria Di Blasio, Ewa Ellis, Roberto Gramignoli, Gastone Castellani, Miriam Capri, Stephen Strom, Christine Nardini, Matteo Cescon, Gian Luca Grazi, Paolo Garagnani
The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes...
March 15, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Nathalie Fournier, Emilie Jacque, Alexandre Fontayne, Delphine Derache, Gilles Dupont, Lucie Verhaeghe, Linda Baptista, Aurélie Dehenne, Anne-Sophie Dezetter, Aurélie Terrier, Alain Longue, Virginie Pochet-Beghin, Cecile Beghin, Sami Chtourou, Christophe de Romeuf
Plasmacytoid dendritic cells (pDCs) play a central role for both innate and adaptive antiviral responses, as they direct immune responses through their unique ability to produce substantial concentrations of type I interferon (IFNs) upon viral encounter while also activating multiple immune cells, including macrophages, DCs, B, natural killer and T cells. Recent evidence clearly indicates that pDCs also play a crucial role in some cancers and several auto-immune diseases. Although treatments are currently available to patients with such pathologies, many are not fully efficient...
March 19, 2018: MAbs
Vid Leko, Smitha Sripathy, Robin L Adrianse, Taylor Loe, Angela Park, Uyen Lao, Eric J Foss, Marisa S Bartolomei, Antonio Bedalov
Forward genetic screens using reporter genes inserted into the heterochromatin have been extensively used to investigate mechanisms of epigenetic control in model organisms. Technologies including short hairpin RNAs (shRNAs) and clustered regularly interspaced short palindromic repeats (CRISPR) have enabled such screens in diploid mammalian cells. Here we describe a large-scale shRNA screen for regulators of X-chromosome inactivation (XCI), using a murine cell line with firefly luciferase and hygromycin resistance genes knocked in at the C-terminus of the methyl CpG binding protein 2 (MeCP2) gene on the inactive X-chromosome (Xi)...
March 2, 2018: Journal of Visualized Experiments: JoVE
Puneet, Hasan Raza Kazmi, Soni Kumari, Satendra Tiwari, A Khanna, Gopeshwar Narayan
Gastric cancer is one of the most common malignancy worldwide. The various genetic and epigenetic events have been found to be associated with its carcinogenesis. The epigenetic is a heritable and transient/reversible change in the gene expression that is not accompanied by modification in the DNA sequence. This event is characterized by the alteration in the promoter CpG island of the gene or histone modification. These events are associated with silencing of critical tumor suppressor gene and activation of oncogenes leading to carcinogenesis...
March 19, 2018: Pathology Oncology Research: POR
Xiaoshan Yu, Bin Zhao, Yanhua Su, Yan Zhang, Jianghui Chen, Wenhui Wu, Qijun Cheng, Xiaorong Guo, Zeyu Zhao, Xiayi Ke, Wangmu Danzeng, Benhua Zhao, Qilin Ma
AIMS: To investigate whether intrauterine organochlorine pesticide (OCP)-dichlorodiphenyltrichloroethane (DDT) exposure could lead to epigenetic alterations by DNA methylation with possible important lifetime health consequences for offspring. MAIN METHODS: We used Illumina Infinium HumanMethylation 450 K BeadChip to explore the pattern of genome-wide DNA methylation containing >485,000 gene sites in cord blood of 24 subjects in a 12 mother-newborn pairs birth cohort...
March 15, 2018: Life Sciences
Rebecca G Smith, Eilis Hannon, Philip L De Jager, Lori Chibnik, Simon J Lott, Daniel Condliffe, Adam R Smith, Vahram Haroutunian, Claire Troakes, Safa Al-Sarraj, David A Bennett, John Powell, Simon Lovestone, Leonard Schalkwyk, Jonathan Mill, Katie Lunnon
INTRODUCTION: Alzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain. METHODS: We performed an epigenome-wide association study to identify differential DNA methylation associated with neuropathology in prefrontal cortex and superior temporal gyrus samples from 147 individuals, replicating our findings in two independent data sets (N = 117 and 740). RESULTS: We identify elevated DNA methylation associated with neuropathology across a 48-kb region spanning 208 CpG sites within the HOXA gene cluster...
March 14, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Ali Movahedi, Jiaxin Zhang, Weibo Sun, Kourosh Mohammadi, Amir Almasi Zadeh Yaghuti, Hui Wei, Xiaolong Wu, Tongming Yin, Qiang Zhuge
Epigenetic modification by DNA methylation is necessary for all cellular processes, including genetic expression events, DNA repair, genomic imprinting and regulation of tissue development. It occurs almost exclusively at the C5 position of symmetric CpG and asymmetric CpHpG and CpHpH sites in genomic DNA. The RNA-directed DNA methylation (RDM1) gene is crucial for heterochromatin and DNA methylation. We overexpressed PtRDM1 gene from Populus trichocarpa to amplify transcripts of orthologous RDM1 in 'Nanlin895' (P...
March 10, 2018: Plant Physiology and Biochemistry: PPB
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