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Histone deacetylase

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https://www.readbyqxmd.com/read/29161081/diet-obesity-and-asthma
#1
Lisa G Wood
Obesity has reached epidemic proportions in many developed countries as Western dietary patterns have been widely adopted. These diets are characterized by excess energy intake as well as regular consumption of processed or "fast" foods and limited consumption of fruit, vegetables, and whole grains. The result is a high intake of saturated fat, refined carbohydrates, and sodium; and a low intake of fiber, vitamins, and other phytochemicals. This type of poor-quality diet has been associated with increased risk of chronic inflammatory diseases, including asthma...
November 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29160373/the-role-of-histone-deacetylase-inhibitors-in-regulation-of-akt-gsk-3%C3%AE-signaling-pathway-in-mice-following-transient-focal-cerebral-ischemia
#2
Bo Zhao, Lian Liu, Yan Leng, Quan Yuan, Jiabao Hou, Yang Wu, Wenwei Gao
PURPOSE: To investigate whether the neuroprotective effect of TSA on cerebral ischemia reperfusion injury is mediated by the activation of Akt/GSK-3β signaling pathway. METHODS: Mice were randomly divided into four groups (n=15): sham group (S); ischemia reperfusion group (IR); ischemia reperfusion and pretreated with TSA group (IR+T); ischemia reperfusion and pretreated with TSA and LY294002 group (IR+T+L). The model of cerebral ischemia reperfusion was established by 1h of MCAO following 24h of reperfusion...
October 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29159826/pharmacological-and-molecular-approaches-for-the-treatment-of-%C3%AE-hemoglobin-disorders
#3
REVIEW
Neelam Lohani, Nupur Bhargava, Anjana Munshi, Sivaprakash Ramalingam
β-hemoglobin disorders, such as β-thalassemia and sickle cell anemia are among the most prevalent inherited genetic disorders worldwide. These disorders are caused by mutations in the gene encoding hemoglobin-β (HBB), a vital protein found in red blood cells (RBCs) that carries oxygen from lungs to all parts of the human body. As a consequence, there has been an enduring interest in this field in formulating therapeutic strategies for the treatment of these diseases. Currently, there is no cure available for hemoglobin disorders, although, some patients have been treated with bone marrow transplantation, whose scope is limited because of the difficulty in finding a histocompatible donor and also due to transplant-associated clinical complications that can arise during the treatment...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29158484/the-hsf1-parp13-parp1-complex-facilitates-dna-repair-and-promotes-mammary-tumorigenesis
#4
Mitsuaki Fujimoto, Ryosuke Takii, Eiichi Takaki, Arpit Katiyar, Ryuichiro Nakato, Katsuhiko Shirahige, Akira Nakai
Poly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair, chromatin structure, and transcription. However, the mechanisms that regulate PARP1 distribution on DNA are poorly understood. Here, we show that heat shock transcription factor 1 (HSF1) recruits PARP1 through the scaffold protein PARP13. In response to DNA damage, activated and auto-poly-ADP-ribosylated PARP1 dissociates from HSF1-PARP13, and redistributes to DNA lesions and DNA damage-inducible gene loci. Histone deacetylase 1 maintains PARP1 in the ternary complex by inactivating PARP1 through deacetylation...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158185/cdk5-mediated-phosphorylation-of-sirt2-contributes-to-depressive-like-behavior-induced-by-social-defeat-stress
#5
Zheng Zhang, Pei Zhang, Guang-Jian Qi, Feng-Juan Jiao, Qing-Zhi Wang, Jian-Guo Yan, Feng He, Qian Zhang, Ze-Xi Lv, Xiang Peng, Hong-Wei Cai, Xiaoqian Chen, Ning Sun, Bo Tian
Major depressive disorder (MDD) is a common, severe and recurrent psychiatric disorder worldwide; however, the underlying neuropathological mechanisms remain elusive. Histone deacetylases (HDACs) appear to play an essential role in depression. As the class III HDACs, Sirt1 and Sirt2 have attracted the most interest in the nervous system. Indeed, chronic stress decreased Sirt1 activity and down-regulated Sirt1 gene expression in MDD. Nevertheless, there is a paucity of literature on the role of Sirt2. To study the role of Sirt2 we established a MDD mouse model in wild type and Sirt2 knockout C57BL/6 mice using social defeat stress (SDS)...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29158005/1-25-oh-2d3-induced-apoptosis-of-human-hepatocellular-carcinoma-cells-in-vitro-and-inhibited-their-growth-in-a-nude-mouse-xenograft-model-by-regulating-histone-deacetylase-2
#6
Jian Huang, Guozhen Yang, Yunzhu Huang, Shu Zhang
The aim of this study was to evaluate the effects of 1,25(OH)2D3 on the apoptosis of human hepatocellular carcinoma (HCC) cells. The effects of 1,25(OH)2D3 on the proliferation and apoptosis of human HCC cells by regulating histone deacetylase 2 (HDAC2) were assessed by MTT assay and flow cytometry. The effects of 1,25(OH)2D3 on the expressions of related proteins in the apoptosis pathway by regulating HDAC2 as well as the mechanism were studied by Western blot and quantitative real-time PCR. A nude mouse model of HCC xenograft was established...
November 17, 2017: Biochimie
https://www.readbyqxmd.com/read/29156785/in-silico-and-in-vitro-identification-of-inhibitory-activities-of-sorafenib-on-histone-deacetylases-in-hepatocellular-carcinoma-cells
#7
Tsang-Pai Liu, Yi-Han Hong, Pei-Ming Yang
Although sorafenib has been approved for treating hepatocellular carcinoma (HCC), clinical results are not satisfactory. Polypharmacology (one drug with multiple molecular targets) is viewed as an attractive strategy for identifying novel mechanisms of a drug and then rationally designing more-effective next-generation therapeutic agents. In this study, a polypharmacological study of sorafenib was performed by mining the next-generation Connectivity Map (CMap) database, CLUE (https://clue.io/). We found that sorafenib may act as a histone deacetylase (HDAC) inhibitor based on similar gene expression profiles...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156195/aml-in-2017-advances-in-clinical-practice
#8
REVIEW
Jacob M Rowe
Numerous advances have been made in the biology and treatment of acute myeloid leukemia (AML) in 2017. These include the integration of the assessment of minimal residual disease (MRD) into clinical practice, the approval and near approval of new agents, improvement in therapy for older patients, and the development of a number of promising new agents, including IDH inhibitors, a Hedgehog signaling pathway inhibitor, and a histone deacetylase inhibitor. In addition, the concept of chemotherapy manipulation is still valid and can increase efficacy in some AML populations, and transplant patterns have shifted, enabling more patients to receive a hematopoietic stem cell transplant...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29155817/analysis-of-the-interactome-of-schistosoma-mansoni-histone-deacetylase-8
#9
Stéphanie Caby, Lucile Pagliazzo, Julien Lancelot, Jean-Michel Saliou, Nicolas Bertheaume, Raymond J Pierce, Emmanuel Roger
BACKGROUND: Histone deacetylase 8 from Schistosoma mansoni (SmHDAC8) is essential to parasite growth and development within the mammalian host and is under investigation as a target for the development of selective inhibitors as novel schistosomicidal drugs. Although some protein substrates and protein partners of human HDAC8 have been characterized, notably indicating a role in the function of the cohesin complex, nothing is known of the partners and biological function of SmHDAC8. METHODOLOGY/PRINCIPAL FINDINGS: We therefore employed two strategies to characterize the SmHDAC8 interactome...
November 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29155171/manganese-chloride-induces-histone-acetylation-changes-in-neuronal-cells-its-role-in-manganese-induced-damage
#10
Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu
Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson's disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl2) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner...
November 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29155146/hdac-inhibitor-suppresses-proliferation-and-invasion-of-breast-cancer-cells-through-regulation-of-mir-200c-targeting-crkl
#11
Xuehai Bian, Zhongxing Liang, Amber Feng, Eric Salgado, Hyunsuk Shim
Although histone deacetylase (HDAC) inhibitors have been shown to effectively induce the inhibition of proliferation and migration in breast cancer, the anticancer mechanism remains poorly understood. Our studies show that miR-200c was significantly downregulated in breast cancer cell lines compared to normal cell lines and inversely correlated with the levels of class IIa HDACs and CRKL. HDAC inhibitors and the ectopic expression of miR-200c as tumor suppressors inhibited the proliferation, invasion, and migration of breast cancer cells by downregulating CRKL...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29153839/asymmetry-between-activation-and-deactivation-during-a-transcriptional-pulse
#12
Lee S S Dunham, Hiroshi Momiji, Claire V Harper, Polly J Downton, Kirsty Hey, Anne McNamara, Karen Featherstone, David G Spiller, David A Rand, Bärbel Finkenstädt, Michael R H White, Julian R E Davis
Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active "on-states," interspersed with periods of inactivity, but these "off-states" and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line...
November 13, 2017: Cell Systems
https://www.readbyqxmd.com/read/29152949/effects-of-valproic-acid-on-sympathetic-activity-and-left-ventricularmyocardial-remodelling-in-rats-during-pressure-overload
#13
Yang Liu, Siyu Li, Zhigang Zhang, Zhanjun Lv, Huijie Jiang, Xiao Tan, Fengquan Liu
Background/aim: Pressure overload induces cardiac remodelling and results in heart failure. Enhanced sympathetic outflow participates in the development of cardiac remodelling for the duration of pressure overload as an independent factor. Valproic acid has recently been shown to reduce neuronal injury and have antiinflammatory and antiapoptotic effects as a histone deacetylase inhibitor. We speculate that the drug plays a specific role in alleviating cardiac remodelling by inhibiting sympathetic activity. Materials and methods: Surgery of partial abdominal aortic constriction was performed on male Sprague-Dawley rats...
November 13, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/29152115/hdac-4-regulates-claudin-2-expression-in-egfr-erk1-2-dependent-manner-to-regulate-colonic-epithelial-cell-differentiation
#14
Rizwan Ahmad, Balawant Kumar, Kaichao Pan, Punita Dhawan, Amar B Singh
In normal colon, claudin-2 expression is restricted to the crypt bottom containing the undifferentiated and proliferative colonocytes. Claudin-2 expression is also upregulated in colorectal cancer (CRC) and promotes carcinogenesis. However, cellular mechanism/s regulated by increased claudin-2 expression during the CRC and mechanism/s regulating this increase remain poorly understood. Epigenetic mechanisms help regulate expression of cancer-associated genes and inhibition of Histone Deacetylases (HDACs) induces cell cycle arrest and differentiation...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152082/panbinostat-decreases-cflip-and-enhances-killing-of-cancer-cells-by-immunotoxin-lmb-100-by-stimulating-the-extrinsic-apoptotic-pathway
#15
Xiu-Fen Liu, Qi Zhou, Raffit Hassan, Ira Pastan
LMB-100 (RG7787) is a recombinant immunotoxin, which kills mesothelin-expressing cancer cells and now being evaluated in phase 1 trials. To enhance the anti-tumor activity of LMB-100, we have searched for agents, already approved for cancer therapy, that can be combined with LMB-100 to increase its efficacy. Panbinostat is a pan-histone deacetylase inhibitor that is used to treat multiple myeloma. We incubated different types of cancer cells with panbinostat and LMB-100 and found that they interacted synergistically to cause cell death...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151363/functional-assessment-of-human-enhancer-activities-using-whole-genome-starr-sequencing
#16
Yuwen Liu, Shan Yu, Vineet K Dhiman, Tonya Brunetti, Heather Eckart, Kevin P White
BACKGROUND: Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome. RESULTS:  In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity...
November 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/29150330/the-structural-requirements-of-histone-deacetylase-inhibitors-c4-modified-saha-analogs-display-dual-hdac6-hdac8-selectivity
#17
Ahmed T Negmeldin, Joseph R Knoff, Mary Kay H Pflum
Histone deacetylase (HDAC) enzymes govern the post-translational acetylation state of lysine residues on protein substrates, leading to regulatory changes in cell function. Due to their role in cancers, HDAC proteins have emerged as promising targets for cancer treatment. Four HDAC inhibitors have been approved as anti-cancer therapeutics, including SAHA (Suberoylanilide hydroxamic acid, Vorinostat, Zolinza). SAHA is a nonselective HDAC inhibitor that targets most of the eleven HDAC isoforms. The nonselectivity of SAHA might account for its clinical side effects, but certainly limits its use as a chemical tool to study cancer-related HDAC cell biology...
October 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#18
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29147952/gemigliptin-a-novel-dipeptidyl-peptidase-iv-inhibitor-exerts-a-synergistic-cytotoxicity-with-the-histone-deacetylase-inhibitor-pxd101-in-thyroid-carcinoma-cells
#19
S H Kim, J G Kang, C S Kim, S-H Ihm, M G Choi, H J Yoo, S J Lee
PURPOSE: The influence of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the histone deacetylase inhibitor PXD101 on survival of thyroid carcinoma cells was investigated. METHODS: SW1736, TPC-1, 8505C and BCPAP human thyroid carcinoma cells were used. To assess cell survival, cell viability, the percentage of viable cells and dead cells, cytotoxic activity, ATP levels and FACS analysis were measured. To validate the impact of gemigliptin combined with PXD101, the interactions were estimated by obtaining combination index in cells treated with two agents...
November 16, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#20
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
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