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https://www.readbyqxmd.com/read/28063323/genetic-and-epigenetic-regulation-on-the-transcription-of-gabrb2-genotype-dependent-hydroxymethylation-and-methylation-alterations-in-schizophrenia
#1
Lu Zong, Lin Zhou, Yu Hou, Lulu Zhang, Wei Jiang, Wenwei Zhang, Lijuan Wang, Xia Luo, Shiqing Wang, Cong Deng, Zhizhen Peng, Shufen Li, Jiming Hu, Hu Zhao, Cunyou Zhao
To improve our understanding of the abnormalities and non-Mendelian inheritance characteristics of schizophrenia, this study examined DNA methylation (5mC) and hydroxymethylation (5hmC) in the schizophrenia-associated GABRB2 gene encoding the type A γ-aminobutyric acid receptor β2 subunit. DNAs from the peripheral white blood cells of 279 schizophrenic patients and 256 controls from the Chinese Han population were examined to reveal that the GABRB2 promoter P1-5mC level which was correlated with olanzapine administration, P2-5mC/5hmC level, and Alu-5mC level which was correlated with administration of ziprasidone or oxcarbazepine, were increased in schizophrenic patients...
December 28, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28062506/wnt-signaling-pathway-inhibitor-sclerostin-inhibits-angiotensin-ii-induced-aortic-aneurysm-and-atherosclerosis
#2
Smriti Murali Krishna, Sai-Wang Seto, Roby J Jose, Jiaze Li, Susan K Morton, Erik Biros, Yutang Wang, Vianne Nsengiyumva, Jan H N Lindeman, Gabriela G Loots, Catherine M Rush, Jeffrey M Craig, Jonathan Golledge
OBJECTIVE: Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. APPROACH AND RESULTS: SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOST(Tg)...
December 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28061437/keap1-nrf2-pathway-in-kidney-cancer-frequent-methylation-of-keap1-gene-promoter-in-clear-renal-cell-carcinoma
#3
Federico Pio Fabrizio, Manuela Costantini, Massimiliano Copetti, Annamaria la Torre, Angelo Sparaneo, Andrea Fontana, Luana Poeta, Michele Gallucci, Steno Sentinelli, Paolo Graziano, Paola Parente, Vincenzo Pompeo, Laura De Salvo, Giuseppe Simone, Rocco Papalia, Francesco Picardo, Teresa Balsamo, Gerardo Paolo Flammia, Domenico Trombetta, Angela Pantalone, Klaas Kok, Ferronika Paranita, Lucia Anna Muscarella, Vito Michele Fazio
The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma)...
4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28039455/a-phase-i-trial-of-azacitidine-and-nanoparticle-albumin-bound-paclitaxel-in-patients-with-advanced-or-metastatic-solid-tumors
#4
Adam L Cohen, Abhijit Ray, Matthew Van Brocklin, David M Burnett, R Chris Bowen, Donna L Dyess, Thomas W Butler, Theresa Dumlao, Hung T Khong
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035374/activation-of-oncogenic-pathways-in-classical-hodgkin-lymphoma-by-decitabine-a-rationale-for-combination-with-small-molecular-weight-inhibitors
#5
Tatjana Maria Swerev, Thomas Wirth, Alexey Ushmorov
DNA methylation is an epigenetic control mechanism that contributes to the specific phenotype and to the oncogenic program of virtually all tumor entities. Although efficacy of demethylating agents in classical Hodgkin lymphoma (cHL) was not specifically tested, a case of regression of relapsed metastatic cHL was described as a fortunate side‑effect of the demethylating agent 5‑azacytidine in a patient with myelodysplastic syndrome. We investigated molecular mechanisms of decitabine (5‑Aza‑dC) antitumor activity in cHL using gene expression profiling followed by gene set enrichment analysis...
December 30, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27998022/the-effects-of-the-dna-methyltranfserases-inhibitor-5-azacitidine-on-ageing-oxidative-stress-and-dna-methylation-of-adipose-derived-stem-cells
#6
Katarzyna Kornicka, Krzysztof Marycz, Monika Marędziak, Krzysztof A Tomaszewski, Jakub Nicpoń
Human adipose tissue is a great source of adult mesenchymal stem cells (MSCs) which are recognized from their ability to self-renew and differentiation into multiple lineages. MSCs have promised a vast therapeutic potential in treatment many diseases including tissue injury and immune disorders. However, their regenerative potential profoundly depends on patients' age. Age-related deterioration of MSC is associated with cellular senescence mainly caused by increased DNA methylation status, accumulation of oxidative stress factors and mitochondria dysfunction...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27965682/stable-epigenetic-variants-selected-from-an-induced-hypomethylated-fragaria-vesca-population
#7
Jihua Xu, Karen K Tanino, Stephen J Robinson
Epigenetic inheritance was transmitted through selection over five generations of extreme early, but not late flowering time phenotypic lines in Fragaria vesca. Epigenetic variation was initially artificially induced using the DNA demethylation reagent 5-azacytidine (5-azaC). It is the first report to explore epigenetic variant selection and phenotypic trait inheritance in strawberry. Transmission frequency of these traits was determined across generations. The early flowering (EF4) and late stolon (LS) phenotypic traits were successfully transmitted across five and three generations through meiosis, respectively...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27942223/silencing-of-mir-1247-by-dna-methylation-promoted-non-small-cell-lung-cancer-cell-invasion-and-migration-by-effects-of-stmn1
#8
Juan Zhang, Jun Fu, Yuliang Pan, Xi Zhang, Liangfang Shen
MicroRNAs (miRNAs) play an important role in cancer development and progression, altering several biological functions by affecting targets through either degradation of mRNAs or suppression of protein translation. One such miRNA, miR-1247, is downregulated in various cancers, but its biological role in non-small-cell lung cancer (NSCLC) is unknown. This study found that the expression of miR-1247 was significantly reduced in NSCLC cell lines and tumor tissues compared with matched normal lung tissues and cell lines as a result of DNA hypermethylation...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27935870/changes-in-the-methylation-status-of-the-oct3-4-nanog-and-sox2-promoters-in-stem-cells-during-regeneration-of-rat-tracheal-epithelium-after-injury
#9
Ying Zhou, Nan Song, Xin Li, Ying Han, Zihan Ren, Jing-Xian Xu, Yu-Chen Han, Fang Li, Xinshan Jia
We investigated the relationship between promoter methylation and tracheal stem cell activation. We developed a model of rat tracheal epithelium regeneration after 5-fluorouracil (5-FU)-induced injury. Using immunohistochemistry and Western blotting, the expression levels of the stem cell pluripotency regulator Oct3/4 and differentiation marker CK14 were measured after 5-FU treatment. The methylation status of the Oct3/4, Nanog, and Sox2 promoters was investigated using methylation-specific PCR. Additionally, the effects of 5-azacytidine (5-azaC), a demethylating agent, on Oct3/4, Nanog, and Sox2 mRNA and protein expression were evaluated...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935410/establishment-of-a-high-throughput-detection-system-for-dna-demethylating-agents
#10
Eriko Okochi-Takada, Naoko Hattori, Akihiro Ito, Tohru Niwa, Mika Wakabayashi, Kana Kimura, Minoru Yoshida, Toshikazu Ushijima
Epigenetic alterations underlie various human disorders, including cancer, and this has resulted in the development of drugs targeting epigenetic alterations. Although DNA demethylating agents are one of the major epigenetic drugs, only two compounds-5-azacytidine (5-aza-CR, azacitidine) and 5-aza-2'-deoxycytidine (5-aza-dC, decitabine)-have obtained clinical approval. Here, we aimed to establish a detection system for DNA demethylating agents suitable for a high-throughput screening (HTS) in mammalian cells...
December 9, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27924400/an-insight-into-the-secondary-metabolism-of-muscodor-yucatanensis-small-molecule-epigenetic-modifiers-induce-expression-of-secondary-metabolism-related-genes-and-production-of-new-metabolites-in-the-endophyte
#11
Masroor Qadri, Yedukondalu Nalli, Shreyans K Jain, Asha Chaubey, Asif Ali, Gary A Strobel, Ram A Vishwakarma, Syed Riyaz-Ul-Hassan
Muscodor spp. are proficient producers of bioactive volatile organic compounds (VOCs) with many potential applications. However, all members of this genus produce varying amounts and types of VOCs which suggests the involvement of epigenetics as a possible explanation. The members of this genus are poorly explored for the production of soluble compounds (extrolites). In this study, the polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes from an endophyte, Muscodor yucatanensis Ni30, were cloned and sequenced...
December 6, 2016: Microbial Ecology
https://www.readbyqxmd.com/read/27913518/treatment-options-for-patients-with-myelodysplastic-syndromes-after-hypomethylating-agent-failure
#12
Hetty E Carraway
The treatment of patients with myelodysplastic syndromes (MDSs) has hinged primarily on supportive care (ie, blood transfusions, colony stimulating agents, iron chelation, etc.) and the US Food and Drug Administration-approved agents, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For patients no longer benefitting from these agents, there is a paucity of effective therapies. The challenges at this time include our limited understanding of the mechanisms of resistance to these therapies and the variables employed to select next best therapies for patients based on: (1) their performance status and medical comorbidities; (2) the molecular feature(s) of their MDS; (3) the prior treatments they have received; and (4) the long-term goal(s)/possibilities for their future treatment (ie, transplant vs no transplant)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#13
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27889521/azacytidine-and-mir156-promote-rooting-in-adult-but-not-in-juvenile-arabidopsis-tissues
#14
Mehdi Massoumi, Frans A Krens, Richard G F Visser, Geert-Jan M De Klerk
Poor adventitious root (AR) formation is a major obstacle in micropropagation and conventional vegetative propagation of many crops. It is affected by many endogenous and exogenous factors. With respect to endogenous factors, the phase change from juvenile to adult has a major influence on AR formation and rooting is usually much reduced or even fully inhibited in adult tissues. It has been reported that the phase change is characterized by an increase in DNA-methylation and a decrease in the expression of microRNA156 (miR156)...
January 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/27877174/dna-methyltransferase-inhibitor-promotes-human-cd4-cd25-h-foxp3-regulatory-t-lymphocyte-induction-under-suboptimal-tcr-stimulation
#15
Chun-Hao Lu, Cheng-Jang Wu, Cheng-Chi Chan, Duc T Nguyen, Kuo-Ray Lin, Syh-Jae Lin, Li-Chen Chen, Jeffrey Jong-Yong Yen, Ming-Ling Kuo
The "master transcription factor" FOXP3 regulates the differentiation, homeostasis, and suppressor function of CD4(+) regulatory T (Treg) cells, which are critical in maintaining immune tolerance. Epigenetic regulation of FOXP3 expression has been demonstrated to be important to Treg cell development, but the induction of human Treg cells through epigenetic modification has not been clearly described. We report that the combination of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and suboptimal T cell receptor (TCR) stimulation promoted CD4(+)CD25(h)FOXP3(+) T cell induction from human CD4(+)CD25(-) T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27872192/the-chromatin-assembly-factor-complex-1-caf1-and-5-azacytidine-5-azac-affect-cell-motility-in-src-transformed-human-epithelial-cells
#16
Akinori Endo, Tony Ly, Raffaella Pippa, Dalila Bensaddek, Armel Nicolas, Angus I Lamond
Tumor invasion into surrounding stromal tissue is a hallmark of high grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness, and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor 5-azacytidine (5-AzaC) potently blocks the increased cell motility and invasiveness induced by Src activation...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27870873/herbivore-induced-dna-demethylation-changes-floral-signalling-and-attractiveness-to-pollinators-in-brassica-rapa
#17
Roman T Kellenberger, Philipp M Schlüter, Florian P Schiestl
Plants have to fine-tune their signals to optimise the trade-off between herbivore deterrence and pollinator attraction. An important mechanism in mediating plant-insect interactions is the regulation of gene expression via DNA methylation. However, the effect of herbivore-induced DNA methylation changes on pollinator-relevant plant signalling has not been systematically investigated. Here, we assessed the impact of foliar herbivory on DNA methylation and floral traits in the model crop plant Brassica rapa...
2016: PloS One
https://www.readbyqxmd.com/read/27868302/reduced-dna-methylation-of-sphingosine-1-phosphate-receptor-5-in-alveolar-macrophages-in-copd-a-potential-link-to-failed-efferocytosis
#18
Jameel Barnawi, Hubertus Jersmann, Rainer Haberberger, Sandra Hodge, Robyn Meech
BACKGROUND AND OBJECTIVE: We previously showed that alveolar macrophages from COPD patients are defective in their ability to phagocytose apoptotic cells ('efferocytosis') and that this defect is potentially linked to the sphingosine-1 phosphate (S1P) system, in particular the sphingosine-1 phosphate receptor 5 (S1PR5). In alveolar macrophages from COPD patients, S1PR5 mRNA expression levels increased and were correlated with both lung function and efferocytosis. However, it us unknown whether these changes are under epigenetic control via DNA methylation or whether DNA methylation directly modulates macrophage function...
November 20, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27863907/evidence-of-epigenetic-tags-in-cardiac-fibrosis
#19
REVIEW
Vincenzo Grimaldi, Maria Rosaria De Pascale, Alberto Zullo, Andrea Soricelli, Teresa Infante, Francesco Paolo Mancini, Claudio Napoli
In cardiac fibrosis, following an injury or a stress, non-functional fibrotic tissue substitutes normal myocardium, thus leading to progressive heart failure. Activated fibroblasts are principal determinants of cardiac fibrosis by producing excessive fibrotic extracellular matrix and causing hypertrophy of cardiomyocytes. Epigenetic changes, such as DNA methylation, histone modifications, and miRNAs have been involved in these mechanisms. Therefore, there is a strong interest in reverting such epigenetic transformations in order to arrest myocardial fibrotic degeneration...
February 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/27853634/dynamic-alterations-of-bone-marrow-cytokine-landscape-of-myelodysplastic-syndromes-patients-treated-with-5-azacytidine
#20
Alena Moudra, Sona Hubackova, Veronika Machalova, Marketa Vancurova, Jiri Bartek, Milan Reinis, Zdenek Hodny, Anna Jonasova
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis frequently progressing into acute myeloid leukemia (AML), with emerging evidence implicating aberrant bone marrow (BM) microenvironment and inflammation-related changes. 5-azacytidine (5-AC) represents standard MDS treatment. Besides inhibiting DNA/RNA methylation, 5-AC has been shown to induce DNA damage and apoptosis in vitro. To provide insights into in vivo effects, we assessed the proinflammatory cytokines alterations during MDS progression, cytokine changes after 5-AC, and contribution of inflammatory comorbidities to the cytokine changes in MDS patients...
2016: Oncoimmunology
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