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Epigenetics pathology

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https://www.readbyqxmd.com/read/29133140/the-histone-methyltransferase-g9a-a-new-therapeutic-target-in-biliary-tract-cancer
#1
Christian Mayr, Katharina Helm, Martin Jakab, Markus Ritter, Rajeev Shrestha, Ramesh Makaju, Andrej Wagner, Martin Pichler, Marlena Beyreis, Stefan Staettner, Tarkan Jaeger, Eckhard Klieser, Tobias Kiesslich, Daniel Neureiter
The histone methyltransferase G9a (EHMT2) is a key enzyme for dimethylation of lysine 9 at histone 3 (H3K9me2), a suppressive epigenetic mark. G9a is over-expressed in tumour cells and contributes to cancer aggressiveness. Biliary tract cancer (BTC) is a rare cancer with dismal prognosis due to a lack of effective therapies. Currently, there are no data on the role of G9a in BTC carcinogenesis. We analysed G9a expression in n=68 BTC patient specimens and correlated the data with clinico-pathological and survival data...
November 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/29133016/dynamic-transcriptional-control-of-macrophage-mirna-signature-via-inflammation-responsive-enhancers-revealed-using-a-combination-of-next-generation-sequencing-based-approaches
#2
Zsolt Czimmerer, Attila Horvath, Bence Daniel, Gergely Nagy, Ixchelt Cuaranta-Monroy, Mate Kiss, Zsuzsanna Kolostyak, Szilard Poliska, Laszlo Steiner, Nikolas Giannakis, Tamas Varga, Laszlo Nagy
MicroRNAs are important components of the post-transcriptional fine-tuning of macrophage gene expression in physiological and pathological conditions. However, the mechanistic underpinnings and the cis-acting genomic factors of how macrophage polarizing signals induce miRNA expression changes are not well characterized. Therefore, we systematically evaluated the transcriptional basis underlying the inflammation-mediated regulation of macrophage microRNome using the combination of different next generation sequencing datasets...
November 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29130966/itraq-based-proteomic-analysis-of-neonatal-kidney-from-offspring-of-protein-restricted-rats-reveals-abnormalities-in-intraflagellar-transport-proteins
#3
Xiaomei Liu, Jun Wang, Linlin Gao, Hao Liu, Caixia Liu
BACKGROUND: It is well recognized that adverse events in utero can impair fetal development and lead to the development of kidney injury and hypertension in adulthood. We previously reported a lower kidney index, glomeruli number, and decreased glomerular filtration rate in intrauterine growth restriction (IUGR) offspring induced by maternal protein malnutrition. To explore the molecular mechanisms linking impaired fetal growth to renal diseases, we investigated differentially expressed proteins (DEPs) in the IUGR neonatal kidneys by isobaric tags for relative and absolute quantitation (iTRAQ) analysis...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29124997/perinatal-exposure-to-environmental-tobacco-smoke-is-associated-with-changes-in-dna-methylation-that-precede-the-adult-onset-of-lung-disease-in-a-mouse-model
#4
Elizabeth Cole, Traci A Brown, Kent E Pinkerton, Britten Postma, Keegan Malany, Mihi Yang, Yang Jee Kim, Raymond F Hamilton, Andrij Holian, Yoon Hee Cho
Prenatal and early-life environmental tobacco smoke (ETS) exposure can induce epigenetic alterations associated with inflammation and respiratory disease. The objective of this study was to address the long-term epigenetic consequences of perinatal ETS exposure on latent respiratory disease risk, which are still largely unknown. C57BL/6 mice were exposed to prenatal and early-life ETS; offspring lung pathology, global DNA, and gene-specific methylation were measured at two adult ages. Significant alterations in global DNA methylation and promoter methylation of IFN-γ and Thy-1 were found in ETS-exposed offspring at 10-12 and 20 weeks of age...
August 2017: Inhalation Toxicology
https://www.readbyqxmd.com/read/29118325/the-mammalian-target-of-rapamycin-and-dna-methyltransferase-1-axis-mediates-vascular-endothelial-dysfunction-in-response-to-disturbed-flow
#5
Yun-Peng Zhang, Yi-Tao Huang, Tse-Shun Huang, Wei Pang, Juan-Juan Zhu, Yue-Feng Liu, Run-Ze Tang, Chuan-Rong Zhao, Wei-Juan Yao, Yi-Shuan Li, Shu Chien, Jing Zhou
The earliest atherosclerotic lesions preferentially develop in arterial regions experienced disturbed blood flow, which induces endothelial expression of pro-atherogenic genes and the subsequent endothelial dysfunction. Our previous study has demonstrated an up-regulation of DNA methyltransferase 1 (DNMT1) and a global hypermethylation in vascular endothelium subjected to disturbed flow. Here, we determined that DNMT1-specific inhibition in arterial wall ameliorates the disturbed flow-induced atherosclerosis through, at least in part, targeting cell cycle regulator cyclin A and connective tissue growth factor (CTGF)...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115895/droplet-based-digital-pcr-and-next-generation-sequencing-for-monitoring-circulating-tumor-dna-a-cancer-diagnostic-perspective
#6
Mathilde Postel, Alice Roosen, Pierre Laurent-Puig, Valerie Taly, Shu-Fang Wang-Renault
Early detection of cancers through the analysis of ctDNA could have a significant impact on morbidity and mortality of cancer patients. However, using ctDNA for early cancer diagnosis is challenging partly due to the low amount of tumor DNA released in the circulation and its dilution within DNA originating from non-tumor cells. Development of new technologies such as droplet-based digital PCR (ddPCR) or optimized next generation sequencing (NGS) has greatly improved the sensitivity, specificity and precision for the detection of rare sequences...
November 8, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29115507/cytochrome-p450-1a1-and-1b1-promoter-cpg-island-methylation-regulates-rat-liver-injury-induced-by-isoniazid
#7
Yanhui Li, Yuhong Li, Guoying Zheng, Lingyan Zhu, Jishun Wang, Shasha Mu, Qi Ren, Fumin Feng
DNA methylation is an important component of epigenetics that is involved in the occurrence and development of a variety of diseases. The present study aimed to clarify the relationship between cytochrome P450 (CYP)1A1 and CYP1B1 promoter CpG island methylation and isoniazid‑induced liver injury in rats, and to explore the possible mechanism, rats were given an intragastric dose of isoniazid (55 mg·kg‑1·d‑1). High performance liquid chromatography was used to analyze the DNA methylation level of the whole genome in liver tissue...
October 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29112861/long-fiber-carbon-nanotubes-replicate-asbestos-induced-mesothelioma-with-disruption-of-the-tumor-suppressor-gene-cdkn2a-ink4a-arf
#8
Tatyana Chernova, Fiona A Murphy, Sara Galavotti, Xiao-Ming Sun, Ian R Powley, Stefano Grosso, Anja Schinwald, Joaquin Zacarias-Cabeza, Kate M Dudek, David Dinsdale, John Le Quesne, Jonathan Bennett, Apostolos Nakas, Peter Greaves, Craig A Poland, Ken Donaldson, Martin Bushell, Anne E Willis, Marion MacFarlane
Mesothelioma is a fatal tumor of the pleura and is strongly associated with asbestos exposure. The molecular mechanisms underlying the long latency period of mesothelioma and driving carcinogenesis are unknown. Moreover, late diagnosis means that mesothelioma research is commonly focused on end-stage disease. Although disruption of the CDKN2A (INK4A/ARF) locus has been reported in end-stage disease, information is lacking on the status of this key tumor suppressor gene in pleural lesions preceding mesothelioma...
November 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29106571/retrieval-induced-upregulation-of-tet3-in-pyramidal-neurons-of-the-dorsal-hippocampus-mediates-cocaine-associated-memory-reconsolidation
#9
Cao Liu, Xue Sun, Zhilin Wang, Qiumin Le, Peipei Liu, Changyou Jiang, Feifei Wang, Lan Ma
Background: Memory retrieval refers to re-exposure to information previously encoded and stored in the brain. Following retrieval, a once-consolidated memory destabilizes and undergoes reconsolidation, during which gene expression changes to restabilize memory. Investigating epigenetic regulation during reconsolidation could provide insights into normal memory formation and pathological memory associated with psychiatric disorders. Methods: We used cocaine-induced conditioned place preference (CPP) to assess the cocaine-associated memory of mice and used chemogenetic methods to manipulate the activity of the pyramidal neurons in the dHC...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29105382/hypoxia-from-placental-development-to-fetal-programming
#10
REVIEW
Lais Fajersztajn, Mariana Matera Veras
Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O2 consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood...
October 16, 2017: Birth defects research
https://www.readbyqxmd.com/read/29104591/melatonin-as-an-anti-inflammatory-agent-modulating-inflammasome-activation
#11
REVIEW
Gaia Favero, Lorenzo Franceschetti, Francesca Bonomini, Luigi Fabrizio Rodella, Rita Rezzani
Inflammation may be defined as the innate response to harmful stimuli such as pathogens, injury, and metabolic stress; its ultimate function is to restore the physiological homeostatic state. The exact aetiology leading to the development of inflammation is not known, but a combination of genetic, epigenetic, and environmental factors seems to play an important role in the pathogenesis of many inflammation-related clinical conditions. Recent studies suggest that the pathogenesis of different inflammatory diseases also involves the inflammasomes, intracellular multiprotein complexes that mediate activation of inflammatory caspases thereby inducing the secretion of proinflammatory cytokines...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29104026/current-insights-into-functions-of-phospholipase-a2-receptor-in-normal-and-cancer-cells-more-questions-than-answers
#12
REVIEW
Olga Sukocheva, Mario Menschikowski, Albert Hagelgans, Nagendra Sastry Yarla, Gabriele Siegert, Pallu Reddanna, Anupam Bishayee
Lipid signaling network was proposed as a potential target for cancer prevention and treatment. Several recent studies revealed that phospholipid metabolising enzyme, phospholipase A2 (PLA2), is a critical regulator of cancer accelerating pathologies and apoptosis in several types of cancers. In addition to functioning as an enzyme, PLA2 can activate a phospholipase A2 receptor (PLA2R1) in plasma membrane. While the list of PLA2 targets extends to glucose homeostasis, intracellular energy balance, adipocyte development, and hepatic lipogenesis, the PLA2R1 downstream effectors are few and scarcely investigated...
November 2, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29100314/genes-encoding-neuropeptide-receptors-are-epigenetic-markers-in-patients-with-head-and-neck-cancer-a-site-specific-analysis
#13
Kiyoshi Misawa, Atsushi Imai, Daiki Mochizuki, Yuki Misawa, Shiori Endo, Seiji Hosokawa, Ryuji Ishikawa, Masato Mima, Kazuya Shinmura, Takeharu Kanazawa, Hiroyuki Mineta
Staging and pathological grading systems are useful but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). To identify potential prognostic markers, we examined the methylation status of eight neuropeptide receptor gene promoters in 231 head and neck squamous cell carcinomas. The NPFFR1, NPFFR2, HCRTR1, HCRTR2, NPY1R, NPY2R, NPY4R, and NPY5R promoters were methylated in 80.5%, 79.2%, 67.1%, 73.2%, 35.1%, 36.4%, 38.5%, and 35.9% of the samples, respectively. In a multivariate Cox proportional hazards analysis, the odds ratio for recurrence was 2...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099948/heritable-sperm-chromatin-epigenetics-a-break-to-remember
#14
Ralph G Meyer, Chelsea Ketchum, Mirella L Meyer-Ficca
Sperm chromatin not only has a unique structure to condense and protect the paternal DNA in transit, but also provides epigenetic information that supports embryonic development. Most of the unique sperm nuclear architecture is formed during the sweeping postmeiotic chromatin remodeling events in spermiogenesis, where the majority of nucleosomes are removed and replaced by protamines. The remaining histones and other chromatin proteins are located in structurally and transcriptionally relevant positions in the genome and carry diverse posttranslational modifications relevant to the control of embryonic gene expression...
November 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29099283/lowly-methylated-region-analysis-identifies-ebf1-as-a-potential-epigenetic-modifier-in-breast-cancer
#15
Nora Fernandez-Jimenez, Athena Sklias, Szilvia Ecsedi, Vincent Cahais, Davide Degli-Esposti, Antonin Jay, Pierre Benoit Ancey, Hae Dong Woo, Hector Hernandez-Vargas, Zdenko Herceg
Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29098769/analyzing-epigenetic-control-of-galectin-expression-indicates-silencing-of-galectin-12-by-promoter-methylation-in-colorectal-cancer
#16
Eva-Maria Katzenmaier, Matthias Kloor, Hans-Joachim Gabius, Johannes Gebert, Juergen Kopitz
Galectins, a class of lectins with specificity for ß-galactoside containing glycoconjugates, modulate several cellular processes that are involved in the control of normal cell growth, differentiation, cell-cell, and cell matrix interactions. Pathological alterations of the galectin expression pattern have been implicated in the development and progression of cancer. We therefore analyzed epigenetic mechanisms for control of galectin expression in 9 colorectal cancer (CRC) cell lines. Our data demonstrate that expression of galectins-1, -2, -7, -8, and -9 can be regulated by histone acetylation in CRC cell lines...
November 3, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29098673/biochemical-diagnosis-in-substance-and-non-substance-addiction
#17
Wenwen Shen, Huifeng Liu, Xiaohu Xie, Haixiong Liu, Wenhua Zhou
An optimal biochemical marker for addiction would be some easily traced molecules in body specimens, which indicates indulgent addictive behaviors, or susceptibility to certain addictive stimuli. In this chapter, we discussed existing literature about possible biomarkers, and classified them into three categories: origin forms and metabolites of substances, markers from biochemical responses to certain addiction, and genetic and epigenetic biomarkers suggesting susceptibility to addiction. In every category, we examined studies concerning certain type of addiction one by one, with focuses mainly on opiates, psychostimulants, and pathological gambling...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29091298/the-mechanism-and-potential-targets-of-class-ii-hdacs-in-angiogenesis
#18
Fei Hou, Dandan Li, Honglian Yu, Qingsheng Kong
Angiogenesis refers to the new blood vessels deriving from the existing blood vessels, and it's a complex regulatory process. Angiogenesis is associated with the normal development of the body and tumor growth and migration. The imbalance of histone deacetylase, as an epigenetic modification, could induce the production of diseases, such as cancer, metabolic diseases, etc., and it also plays an important role in angiogenesis. Many researches indicate that class II HDACs nuclear shuttle and its phosphorylation are necessary for the diseases and the protection of the collective itself...
November 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29088923/oxidative-modifications-in-tissue-pathology-and-autoimmune-disease
#19
Mei-Ling Yang, Hester Doyle, Steven G Clarke, Kevan Herold, Mark Mamula
SIGNIFICANCE: Various autoimmune syndromes are characterized by abnormalities found at the level of tissues and cells, as well as by microenvironmental influences, such as reactive oxygen species (ROS), that alter intracellular metabolism and protein expression. Moreover, the convergence of genetic, epigenetic, and even environmental influences can result in B and T lymphocyte autoimmunity and tissue pathology. Recent Advances: This review will describe how oxidative stress to cells and tissues may alter posttranslational protein modifications, both directly and indirectly, as well as potentially lead to aberrant gene expression...
October 31, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29081381/inflammageing-and-metaflammation-the-yin-and-yang-of-type-2-diabetes
#20
REVIEW
Francesco Prattichizzo, Valeria De Nigris, Rosangela Spiga, Elettra Mancuso, Lucia La Sala, Roberto Antonicelli, Roberto Testa, Antonio Domenico Procopio, Fabiola Olivieri, Antonio Ceriello
Type 2 diabetes mellitus (T2DM) is characterised by chronic low-grade inflammation, recently referred to as 'metaflammation', a relevant factor contributing to the development of both diabetes and its complications. Nonetheless, 'canonical' anti-inflammatory drugs do not yield satisfactory results in terms of prevention of diabetes progression and of cardiovascular events, suggesting that the causal mechanisms fostering metaflammation deserve further research to identify new druggable targets. Metaflammation resembles ageing-induced low-grade inflammation, previously referred to as inflammageing, in terms of clinical presentation and the molecular profile, pointing to a common aetiology for both conditions...
October 31, 2017: Ageing Research Reviews
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