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Epigenetics pathology

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https://www.readbyqxmd.com/read/28549270/the-effects-of-early-life-adversity-on-the-immune-system
#1
REVIEW
Martha M C Elwenspoek, Annette Kuehn, Claude P Muller, Jonathan D Turner
Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences...
May 17, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28548108/drugging-the-pain-epigenome
#2
REVIEW
Ellen Niederberger, Eduard Resch, Michael J Parnham, Gerd Geisslinger
More than 20% of adults worldwide experience different types of chronic pain, which are frequently associated with several comorbidities and a decrease in quality of life. Several approved painkillers are available, but current analgesics are often hampered by insufficient efficacy and/or severe adverse effects. Consequently, novel strategies for safe, highly efficacious treatments are highly desirable, particularly for chronic pain. Epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs (miRNAs) strongly affect the regulation of gene expression, potentially for long periods over years or even generations, and have been associated with pathophysiological pain...
May 26, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28545737/microrna-146a-governs-fibroblast-activation-and-joint-pathology-in-arthritis
#3
Victoria Saferding, Antonia Puchner, Eliana Goncalves-Alves, Melanie Hofmann, Michael Bonelli, Julia S Brunner, Emine Sahin, Birgit Niederreiter, Silvia Hayer, Hans P Kiener, Elisa Einwallner, Ramzi Nehmar, Raphael Carapito, Philippe Georgel, Marije I Koenders, Mark Boldin, Gernot Schabbauer, Mariola Kurowska-Stolarska, Günter Steiner, Josef S Smolen, Kurt Redlich, Stephan Blüml
Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo. Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation...
May 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28544151/the-emt-spectrum-and-therapeutic-opportunities
#4
REVIEW
Dominic Chih-Cheng Voon, Ruby Yun-Ju Huang, Rebecca A Jackson, Jean Paul Thiery
Carcinomas are phenotypically arrayed along an EMT spectrum, a developmental program currently exploited to understand the acquisition of drug resistance through a re-routing of growth factor signalling. This review collates the current approaches employed in developing therapeutics against cancer-associated EMT, and provides an assessment of their respective strengths and drawbacks. We reflect on the close relationship between EMT and chemoresistance against current targeted therapeutics, with a special focus on the epigenetic mechanisms that links these processes...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#5
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#6
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28532996/histone-methyltransferase-g9a-promotes-liver-cancer-development-by-epigenetic-silencing-of-tumor-suppressor-gene-rarres3
#7
Lai Wei, David Kung-Chun Chiu, Felice Ho-Ching Tsang, Dicky Cheuk-Ting Law, Carol Lai-Hung Cheng, Sandy Leung-Kuen Au, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. Epigenetic deregulation is a common trait of human HCC. G9s is an important epigenetics regulator. However, its roles in liver carcinogenesis remain to be investigated. METHODS: Gene expressions were determined by RNA-Seq and qRT-PCR. G9a knockdown and knockout cell lines were established by lentiviral-based shRNA and CRISPR/Cas9 gene editing system. Tumor promoting functions of G9a was studied by both in HCC cell lines and nude mice model...
May 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28526543/thyroid-hormone-biosynthesis-machinery-is-altered-in-the-ischemic-myocardium-an-epigenomic-study
#8
Carolina Gil-Cayuela, Esther Roselló-LLetí, Estefanía Tarazón, Ana Ortega, Juan Sandoval, Luis Martínez-Dolz, Juan Cinca, Esther Jorge, José Ramón González-Juanatey, Francisca Lago, Miguel Rivera, Manuel Portolés
BACKGROUND: Abnormal thyroid hormone (TH) metabolism is significantly associated with impaired left ventricular (LV) function and death. Although TH was traditionally thought to be produced exclusively by the thyroid gland, an increasing number of studies report TH production in other tissues. Based on these findings, we evaluated whether the genes required for TH biosynthesis are expressed in the human heart, and whether their expression is altered in patients with ischemic cardiomyopathy (ICM) and is related to epigenetic variations...
May 11, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28524065/microrna-in-skin-diseases
#9
Tatiana G Ruksha, Anna V Komina, Nadezhda V Palkina
MicroRNAs are essential regulators of various cellular processes such as cell growth, differentiation, apoptosis, and the immune response, acting as factors for translational repression and/or degradation of target messenger RNA. Currently, microRNAs are considered as promising biomarkers and therapeutic targets for different pathological conditions. Skin may serve as a convenient model for microRNA modulation studies due to the comparatively easy access to targets cells. Cutaneous diseases are characterized by multiple intercellular communication pathways, triggered by diverse stimuli and mediated by heterogenous regulators, including microRNAs...
May 19, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28523562/bioinformatics-tools-for-genome-wide-epigenetic-research
#10
Vladimir Espinosa Angarica, Antonio Del Sol
Epigenetics play a central role in the regulation of many important cellular processes, and dysregulations at the epigenetic level could be the source of serious pathologies, such as neurological disorders affecting brain development, neurodegeneration, and intellectual disability. Despite significant technological advances for epigenetic profiling, there is still a need for a systematic understanding of how epigenetics shapes cellular circuitry, and disease pathogenesis. The development of accurate computational approaches for analyzing complex epigenetic profiles is essential for disentangling the mechanisms underlying cellular development, and the intricate interaction networks determining and sensing chromatin modifications and DNA methylation to control gene expression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#11
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28516431/a-comparison-of-neuroimaging-abnormalities-in-multiple-sclerosis-major-depression-and-chronic-fatigue-syndrome-myalgic-encephalomyelitis-is-there-a-common-cause
#12
REVIEW
Gerwyn Morris, Michael Berk, Basant K Puri
There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28515464/systems-immunology-of-diabetes-tuberculosis-comorbidity-reveals-signatures-of-disease-complications
#13
Cesar A Prada-Medina, Kiyoshi F Fukutani, Nathella Pavan Kumar, Leonardo Gil-Santana, Subash Babu, Flávio Lichtenstein, Kim West, Shanmugam Sivakumar, Pradeep A Menon, Vijay Viswanathan, Bruno B Andrade, Helder I Nakaya, Hardy Kornfeld
Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515341/bet-bromodomain-inhibition-suppresses-innate-inflammatory-and-profibrotic-transcriptional-networks-in-heart-failure
#14
Qiming Duan, Sarah McMahon, Priti Anand, Hirsh Shah, Sean Thomas, Hazel T Salunga, Yu Huang, Rongli Zhang, Aarathi Sahadevan, Madeleine E Lemieux, Jonathan D Brown, Deepak Srivastava, James E Bradner, Timothy A McKinsey, Saptarsi M Haldar
Despite current standard of care, the average 5-year mortality after an initial diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new therapeutic approaches. Previous studies demonstrated that the epigenetic reader protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target in cancer, functions as a critical coactivator of pathologic gene transactivation during cardiomyocyte hypertrophy. However, the therapeutic relevance of these findings to human disease remained unknown...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28513547/epigenetic-regulation-of-telomere-maintenance-for-therapeutic-interventions-in-gliomas
#15
REVIEW
Elisabeth Naderlinger, Klaus Holzmann
High-grade astrocytoma of WHO grade 4 termed glioblastoma multiforme (GBM) is a common human brain tumor with poor patient outcome. Astrocytoma demonstrates two known telomere maintenance mechanisms (TMMs) based on telomerase activity (TA) and on alternative lengthening of telomeres (ALT). ALT is associated with lower tumor grades and better outcome. In contrast to ALT, regulation of TA in tumors by direct mutation and epigenetic activation of the hTERT promoter is well established. Here, we summarize the genetic background of TMMs in non-malignant cells and in cancer, in addition to clinical and pathological features of gliomas...
May 17, 2017: Genes
https://www.readbyqxmd.com/read/28509412/-three-hits-hypothesis-for-developmental-origins-of-health-and-diseases-in-view-of-cardiovascular-abnormalities
#16
REVIEW
Xiang Li, Mengshu Zhang, Xinghua Pan, Zhice Xu, Miao Sun
"Fetal Origins of Adult Diseases" (FOAD) or "Barker hypothesis," also known as the developmental origins of health and diseases (DoHaD), was initially proposed by David Barker in the 1980s. Progress in past 2 to 3 decades demonstrated that many adult disorders, including hypertension, diabetes, obesity, cancer, and others, could be linked to poor development resulting from in utero insults. Utero-environments play a critical role in fetal development. Because the placenta and umbilical cord are the only important connections between the fetus and mother in the uterus, this review pays special attention to recent research and progress in the study of the relationship between those tissues and FOAD...
May 16, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28507795/digital-analysis-and-epigenetic-regulation-of-the-signature-of-rejection-in-colorectal-cancer
#17
Viktor H Koelzer, Lena Sokol, Stefan Zahnd, Lucine Christe, Heather Dawson, Martin D Berger, Daniel Inderbitzin, Inti Zlobec, Alessandro Lugli
The immune system plays a pivotal role in the development and progression of colorectal cancer (CRC). Tumor immune rejection has been previously linked to the activation of the interferon-stimulated genes (ISG) STAT1, IRF-5 and IRF-1. Specific immunoregulatory microRNAs (miRNAs) may impact the expression of these ISG in the tumor microenvironment. In this translational study, we develop a digital image analysis protocol to identify the ISG-gene expression signature and investigate miRNA expression in the immediate environment of invading cancer cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28504961/wnt-%C3%AE-catenin-pathway-in-arrhythmogenic-cardiomyopathy
#18
REVIEW
Alessandra Lorenzon, Martina Calore, Giulia Poloni, Leon J De Windt, Paola Braghetta, Alessandra Rampazzo
Wnt/β-catenin signaling pathway plays essential roles in heart development as well as cardiac tissue homoeostasis in adults. Abnormal regulation of this signaling pathway is linked to a variety of cardiac disease conditions, including hypertrophy, fibrosis, arrhythmias, and infarction. Recent studies on genetically modified cellular and animal models document a crucial role of Wnt/β-catenin signaling in the molecular pathogenesis of arrhythmogenic cardiomyopathy (AC), an inherited disease of intercalated discs, typically characterized by ventricular arrhythmias and progressive substitution of the myocardium with fibrofatty tissue...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28501774/tuning-of-major-signaling-networks-tgf-%C3%AE-wnt-notch-and-hedgehog-by-mirnas-in-human-stem-cells-commitment-to-different-lineages-possible-clinical-application
#19
REVIEW
Sedigheh Fekri Aval, Hajie Lotfi, Roghayeh Sheervalilou, Nosratollah Zarghami
Two distinguishing characteristics of stem cells, their continuous division in the undifferentiated state and growth into any cell types, are orchestrated by a number of cell signaling pathways. These pathways act as a niche factor in controlling variety of stem cells. The core stem cell signaling pathways include Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically regulate the self-renewal and survival of cancer stem cells. Conversely, stem cells' main properties, lineage commitment and stemness, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulatory events...
May 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28501566/dna-methylation-regulated-gene-expression-in-organ-fibrosis
#20
REVIEW
Xiangyu Zhang, Min Hu, Xing Lyu, Chun Li, Victor J Thannickal, Yan Y Sanders
DNA methylation is a major epigenetic mechanism to regulate gene expression. Epigenetic regulation, including DNA methylation, histone modifications and RNA interference, results in heritable changes in gene expression independent of alterations in DNA sequence. Epigenetic regulation often occurs in response to aging and environment stimuli, including exposures and diet. Studies have shown that DNA methylation is critical in the pathogenesis of fibrosis involving multiple organs sytems, contributing to significant morbidity and mortality...
May 10, 2017: Biochimica et Biophysica Acta
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