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DNA methylation immune response

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https://www.readbyqxmd.com/read/28771594/patients-experiencing-statin-induced-myalgia-exhibit-a-unique-program-of-skeletal-muscle-gene-expression-following-statin-re-challenge
#1
Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago R Vera, Hannah Fish-Trotter, Robert W Williams, Richard D Childress, Rajendra Raghow
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls...
2017: PloS One
https://www.readbyqxmd.com/read/28756583/phytopathogen-induced-changes-to-plant-methylomes
#2
REVIEW
Tarek Hewezi, Vince Pantalone, Morgan Bennett, C Neal Stewart, Tessa M Burch-Smith
DNA methylation is a dynamic and reversible type of epigenetic mark that contributes to cellular physiology by affecting transcription activity, transposon mobility and genome stability. When plants are infected with pathogens, plant DNA methylation patterns can change, indicating an epigenetic interplay between plant host and pathogen. In most cases methylation can change susceptibility. While DNA hypomethylation appears to be a common phenomenon during the susceptible interaction, the levels and patterns of hypomethylation in transposable elements and genic regions may mediate distinct responses against various plant pathogens...
July 29, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28754822/epigenetic-research-in-multiple-sclerosis-progress-challenges-and-opportunities
#3
Galina Zheleznyakova, Eliane Piket, Francesco Marabita, Majid Pahlevan Kakhki, Ewoud Ewing, Sabrina Ruhrmann, Maria Needhamsen, Maja Jagodic, Lara Kular
Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease...
July 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28753533/role-of-traf3-in-neurological-and-cardiovascular-diseases-an-overview-of-recent-studies
#4
Natalia Cullell, Elena Muiño, Caty Carrera, Nuria Torres, Jerzy Krupinski, Israel Fernandez-Cadenas
Tumour necrosis factor receptor-associated factor 3 (TRAF3) is a member of the TRAF adaptor protein family, which exerts different effects on the cell depending on the receptor to which it binds and the cell type in which it is expressed. TRAF3 is a major regulator of the innate immune response. To perform its functions properly, TRAF3 is transcriptionally and epigenetically regulated. At the transcriptional level, TRAF3 expression has been associated with neurological and cardiovascular diseases including stroke, among other pathologies...
July 28, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/28744851/post-translational-regulation-of-antiviral-innate-signaling
#5
REVIEW
Yilong Zhou, Chenxi He, Wang Lin, Baoxue Ge
The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required...
July 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28742980/disease-relevant-modifications-of-the-methylome-and-transcriptome-by-particulate-matter-pm2-5-from-biomass-combustion
#6
Katharina Heßelbach, Gwang-Jin Kim, Stephan Flemming, Thomas Häupl, Marc Bonin, Regina Dornhof, Stefan Günther, Irmgard Merfort, Matjaz Humar
Exposure to particulate matter (PM) is recognized as a major health hazard, but molecular responses are still insufficiently described. We analyzed the epigenetic impact of ambient PM2.5 from biomass combustion on the methylome of primary human bronchial epithelial BEAS-2B cells using the Illumina HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix HG-U133 Plus 2.0 Array. PM2.5 induced genome wide alterations of the DNA methylation pattern, including differentially methylated CpGs in the promoter region associated with CpG islands...
July 25, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28739824/epigenetic-mechanisms-regulate-innate-immunity-against-uropathogenic-and-commensal-like-escherichia-coli-in-the-surrogate-insect-model-galleria-mellonella
#7
Miriam Heitmueller, André Billion, Ulrich Dobrindt, Andreas Vilcinskas, Krishnendu Mukherjee
Innate immunity-related genes in humans are activated during urinary tract infections (UTIs) caused by pathogenic strains of Escherichia coli but are suppressed by commensals. Epigenetic mechanisms play a pivotal role in the regulation of gene expression in response to environmental stimuli. To determine whether epigenetic mechanisms can explain the different behaviors of pathogenic and commensal bacteria, we infected larvae of the greater wax moth Galleria mellonella, a widely-used model insect host, with a uropathogenic E...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28738836/metabolism-associated-danger-signal-induced-immune-response-and-reverse-immune-checkpoint-activated-cd40-monocyte-differentiation
#8
REVIEW
Jin Dai, Pu Fang, Jason Saredy, Hang Xi, Cueto Ramon, William Yang, Eric T Choi, Yong Ji, Wei Mao, Xiaofeng Yang, Hong Wang
Adaptive immunity is critical for disease progression and modulates T cell (TC) and antigen-presenting cell (APC) functions. Three signals were initially proposed for adaptive immune activation: signal 1 antigen recognition, signal 2 co-stimulation or co-inhibition, and signal 3 cytokine stimulation. In this article, we propose to term signal 2 as an immune checkpoint, which describes interactions of paired molecules leading to stimulation (stimulatory immune checkpoint) or inhibition (inhibitory immune checkpoint) of an immune response...
July 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28714863/dna-methylation-based-immune-response-signature-improves-patient-diagnosis-in-multiple-cancers
#9
Jana Jeschke, Martin Bizet, Christine Desmedt, Emilie Calonne, Sarah Dedeurwaerder, Soizic Garaud, Alexander Koch, Denis Larsimont, Roberto Salgado, Gert Van den Eynden, Karen Willard Gallo, Gianluca Bontempi, Matthieu Defrance, Christos Sotiriou, François Fuks
BACKGROUND: The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS: MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28714605/epigenetic-alterations-and-prenatal-maternal-depression
#10
REVIEW
Zsofia Nemoda, Moshe Szyf
Major depressive disorder of the mother affects 6 to 17% of pregnancies worldwide and can lead to negative outcomes, such as preterm delivery and later mental health problems of the child. It has been proposed that developmental programming has long-lasting effects in the offspring that might be mediated by epigenetic mechanisms, such as DNA methylation. Altered stress regulation or impaired immunological function of the mother can potentially affect DNA methylation processes of the fetus, changing gene expression levels in utero...
July 17, 2017: Birth defects research
https://www.readbyqxmd.com/read/28704659/preheating-mitigates-cadmium-toxicity-in-zebrafish-livers-evidence-from-promoter-demethylation-gene-transcription-to-biochemical-levels
#11
Jia-Lang Zheng, Sai-Nan Guo, Shuang-Shuang Yuan, Hu Xia, Qing-Ling Zhu, Zhen-Ming Lv
The working hypothesis for this study was that moderate heat stress would alleviate the deleterious effects of subsequent cadmium (Cd) exposure on fish. Thus, zebrafish (Danio rerio) were subjected to water maintained at 26°C and 34°C for 4days, and then exposed to 0 or 200μg/L Cd for 1 week at 26°C. Multiple indicators were measured from livers of zebrafish at different levels, including DNA, RNA, protein and enzymatic activity associated with oxidative stress, inflammation and metal transport. The ameliorative effect of preheatinging on Cd toxicity was demonstrated...
September 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28704530/a-complex-association-between-dna-methylation-and-gene-expression-in-human-placenta-at-first-and-third-trimesters
#12
Yen Ching Lim, Jie Li, Yiyun Ni, Qi Liang, Junjiao Zhang, George S H Yeo, Jianxin Lyu, Shengnan Jin, Chunming Ding
The human placenta is a maternal-fetal organ essential for normal fetal development and maternal health. During pregnancy, the placenta undergoes many structural and functional changes in response to fetal needs and environmental exposures. Previous studies have demonstrated widespread epigenetic and gene expression changes from early to late pregnancy. However, on the global level, how DNA methylation changes impact on gene expression in human placenta is not yet well understood. We performed DNA methylome analysis by reduced representation bisulfite sequencing (RRBS) and gene expression analysis by RNA-Seq for both first and third trimester human placenta tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28698603/identification-of-differentially-methylated-brca1-and-crisp2-dna-regions-as-blood-surrogate-markers-for-cardiovascular-disease
#13
Geoffrey Istas, Ken Declerck, Maria Pudenz, Katarzyna Szarc Vel Szic, Veronica Lendinez-Tortajada, Montserrat Leon-Latre, Karen Heyninck, Guy Haegeman, Jose A Casasnovas, Maria Tellez-Plaza, Clarissa Gerhauser, Christian Heiss, Ana Rodriguez-Mateos, Wim Vanden Berghe
Genome-wide Illumina InfiniumMethylation 450 K DNA methylation analysis was performed on blood samples from clinical atherosclerosis patients (n = 8) and healthy donors (n = 8) in the LVAD study (NCT02174133, NCT01799005). Multiple differentially methylated regions (DMR) could be identified in atherosclerosis patients, related to epigenetic control of cell adhesion, chemotaxis, cytoskeletal reorganisations, cell proliferation, cell death, estrogen receptor pathways and phagocytic immune responses...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698226/loss-of-dna-methylation-in-zebrafish-embryos-activates-retrotransposons-to-trigger-antiviral-signaling
#14
Yelena Chernyavskaya, Raksha Mudbhary, Chi Zhang, Debra Tokarz, Vinitha Jacob, Smita Gopinath, Xiaochen Sun, Shuang Wang, Elena Magnani, Bhavani P Madakashira, Jeffrey A Yoder, Yujin Hoshida, Kirsten C Sadler
Complex cytoplasmic nucleotide-sensing mechanisms can recognize foreign DNA based on a lack of methylation and initiate an immune response to clear the infection. Zebrafish embryos with global DNA hypomethylation caused by mutations in the ubiquitin-like with PHD and ring finger domains 1 (uhrf1) or DNA methyltransferase 1 (dnmt1) genes exhibit a robust interferon induction characteristic of the first line of defense against viral infection. We found that this interferon induction occurred in non-immune cells and examined whether intracellular viral sensing pathways in these cells were the trigger...
August 15, 2017: Development
https://www.readbyqxmd.com/read/28696237/persistent-loss-of-hbv-markers-in-serum-without-cellular-immunity-by-combination-of-peg-ifn-plus-etv-therapy-in-humanized-mice
#15
Takuro Uchida, Michio Imamura, C Nelson Hayes, Nobuhiko Hiraga, Hiromi Kan, Masataka Tsuge, Hiromi Abe-Chayama, Yizhou Zhang, Grace Naswa Makokha, Hiroshi Aikata, Daiki Miki, Hidenori Ochi, Yuji Ishida, Chise Tateno, Kazuaki Chayama
Nucleot(s)ide analogues and peg-interferon (PEG-IFN) treatment are the only approved therapies for chronic hepatitis B virus (HBV) infection. However, complete eradication of the virus, as indicated by persistent loss of hepatitis B surface antigen (HBsAg), is rare among treated patients. This is due to long-term persistence of the HBV genome in infected hepatocytes in the form of covalently closed circular DNA (cccDNA). In this study, we investigated whether administration of a large dose of a nucleoside analogue in combination with PEG-IFN can achieve long term loss of HBsAg in human hepatocyte chimeric mice...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28693799/the-current-value-of-determining-the-mismatch-repair-status-of-colorectal-cancer-a-rationale-for-routine-testing
#16
REVIEW
E Ryan, K Sheahan, B Creavin, H M Mohan, D C Winter
Colorectal Cancer (CRC) is the third most prevalent cancer in men and women. Up to 15% of CRCs display microsatellite instability (MSI). MSI is reflective of a deficient mismatch repair (MMR) system and is most commonly caused by hypermethylation of the MLH1 promoter. However, it may also be due to autosomal dominant constitutional mutations in DNA MMR, termed Lynch Syndrome. MSI may be diagnosed via polymerase chain reaction (PCR) or alternatively, immunohistochemistry (IHC) can identify MMR deficiency (dMMR)...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28678605/the-early-pregnancy-placenta-foreshadows-dna-methylation-alterations-of-solid-tumors
#17
Akpéli V Nordor, Djamel Nehar-Belaid, Sophie Richon, David Klatzmann, Dominique Bellet, Virginie Dangles-Marie, Thierry Fournier, Martin J Aryee
The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis-while surviving hypoxia-, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors. We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28648661/de-novo-epigenetic-programs-inhibit-pd-1-blockade-mediated-t-cell-rejuvenation
#18
Hazem E Ghoneim, Yiping Fan, Ardiana Moustaki, Hossam A Abdelsamed, Pradyot Dash, Pranay Dogra, Robert Carter, Walid Awad, Geoff Neale, Paul G Thomas, Ben Youngblood
Immune-checkpoint-blockade (ICB)-mediated rejuvenation of exhausted T cells has emerged as a promising approach for treating various cancers and chronic infections. However, T cells that become fully exhausted during prolonged antigen exposure remain refractory to ICB-mediated rejuvenation. We report that blocking de novo DNA methylation in activated CD8 T cells allows them to retain their effector functions despite chronic stimulation during a persistent viral infection. Whole-genome bisulfite sequencing of antigen-specific murine CD8 T cells at the effector and exhaustion stages of an immune response identified progressively acquired heritable de novo methylation programs that restrict T cell expansion and clonal diversity during PD-1 blockade treatment...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28642826/elucidation-of-the-role-of-lectin-like-oxldl-receptor-1-in-the-metabolic-responses-of-macrophages-to-human-oxldl
#19
Danielle W Kimmel, William P Dole, David E Cliffel
Atherogenesis is the narrowing of arteries due to plaque build-up that results in cardiovascular disease that can lead to death. The macrophage lectin-like oxidized LDL receptor-1 (LOX-1), also called the oxidized low-density lipoprotein receptor 1 (OLR1), is currently thought to aid in atherosclerotic disease progression; therefore metabolic studies have potential to both provide mechanistic validation for the role of LOX-1 in disease progression and provide valuable information regarding biomarker strategies and clinical imaging...
2017: Journal of Lipids
https://www.readbyqxmd.com/read/28634372/dna-methylation-changes-in-endometrium-and-correlation-with-gene-expression-during-the-transition-from-pre-receptive-to-receptive-phase
#20
Viktorija Kukushkina, Vijayachitra Modhukur, Marina Suhorutšenko, Maire Peters, Reedik Mägi, Nilufer Rahmioglu, Agne Velthut-Meikas, Signe Altmäe, Francisco J Esteban, Jaak Vilo, Krina Zondervan, Andres Salumets, Triin Laisk-Podar
The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle...
June 20, 2017: Scientific Reports
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