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https://www.readbyqxmd.com/read/27915160/histone-deacetylase-9-plays-a-role-in-the-antifibrogenic-effect-of-astaxanthin-in-hepatic-stellate-cells
#1
Yue Yang, Minkyung Bae, Young-Ki Park, Yoojin Lee, Tho X Pham, Swetha Rudraiah, José Manautou, Sung I Koo, Ji-Young Lee
Activation of hepatic stellate cells (HSCs) is critical for liver fibrosis development. Previously, we showed that astaxanthin (ASTX), a xanthophyll carotenoid, has antifibrogenic effects in LX-2 cells, a human HSC cell line. We sought to determine the effect of ASTX on HSC activation, and to identify molecular mediators that are critically involved in the processes. ASTX prevented the activation of mouse primary HSCs, as evidenced by attenuated induction of procollagen type I α1. In human primary HSCs, ASTX also inhibited transforming growth factor β1 (TGFβ1)-induced fibrogenic gene expression...
November 12, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27914010/recruitment-by-the-repressor-freud-1-of-histone-deacetylase-brg1-chromatin-remodeling-complexes-to-strengthen-htr1a-gene-repression
#2
Tatiana Souslova, Kim Mirédin, Anne M Millar, Paul R Albert
Five-prime repressor element under dual repression binding protein-1 (Freud-1)/CC2D1A is genetically linked to intellectual disability and implicated in neuronal development. Freud-1 represses the serotonin-1A (5-HT1A) receptor gene HTR1A by histone deacetylase (HDAC)-dependent or HDAC-independent mechanisms in 5-HT1A-negative (e.g., HEK-293) or 5-HT1A-expressing cells (SK-N-SH), respectively. To identify the underlying mechanisms, Freud-1-associated proteins were affinity-purified from HEK-293 nuclear extracts and members of the Brg1/SMARCCA chromatin remodeling and Sin3A-HDAC corepressor complexes were identified...
December 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27913949/epigenetic-cpg-methylation-of-the-promoter-and-reactivation-of-the-expression-of-gstp1-by-astaxanthin-in-human-prostate-lncap-cells
#3
Yuqing Yang, Francisco Fuentes, Limin Shu, Chao Wang, Doug Pung, Wenji Li, Chengyue Zhang, Yue Guo, Ah-Ng Kong
Astaxanthin (AST), a red dietary carotenoid, has synergistic antioxidant effects with polyunsaturated fatty acids at low concentrations via Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2)/antioxidant response element (ARE) signaling. In addition, chromatin remodeling and DNA methylation-based gene silencing represent a common mechanism in prostate carcinogenesis and tumor progression from normal cells to pre-initiated cells and ultimately to invasive carcinoma. Therefore, the control of epigenetic modification and the transcriptional/translational control of the activation of Nrf2 and Nrf2-target genes, including glutathione S-transferases (GSTs), appear to be an important mechanism that protects cells against injuries from oxidative stress and cancer development...
December 2, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27913583/epigenetic-control-of-microsomal-prostaglandin-e-synthase-1-by-hdac-mediated-recruitment-of-p300
#4
Christian Fork, Andrea E Vasconez, Patrick Janetzko, Carlo Angioni, Yannick Schreiber, Nerea Ferreiros, Gerd Geisslinger, Matthias S Leisegang, Dieter Steinhilber, Ralf P Brandes
: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medicine to treat pain, fever, inflammation and to inhibit platelet function. Understanding the expression regulation of enzymes of the prostanoid pathway is of great medical relevance. Histone acetylation crucially controls gene expression. We set out to identify the impact of histone deacetylases (HDACs) on the generation of prostanoids and examine the consequences on vascular function. Inhibition of HDACs (HDACi) with the pan HDAC inhibitor SAHA attenuated prostaglandin E2 (PGE2) generation in the murine vasculature and in human vascular smooth muscle cells...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27913271/histone-deacetylases-hdac-in-physiological-and-pathological-bone-remodelling
#5
REVIEW
M D Cantley, A C W Zannettino, P M Bartold, D P Fairlie, D R Haynes
Histone deacetylases (HDACs)(2) play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi)(3) that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are currently being studied also for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes...
November 29, 2016: Bone
https://www.readbyqxmd.com/read/27913254/quetiapine-treatment-reverses-depressive-like-behavior-and-reduces-dna-methyltransferase-activity-induced-by-maternal-deprivation
#6
Zuleide M Ignácio, Gislaine Z Réus, Helena M Abelaira, Amanda L Maciel, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Fernanda F Gava, Samira S Valvassori, André F Carvalho, João Quevedo
Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus...
November 29, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#7
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27910887/energy-metabolism-regulated-by-hdac-inhibitor-attenuates-cardiac-injury-in-hemorrhagic-rat-model
#8
Qiyuan Kuai, Chunyan Wang, Yanbing Wang, Weijing Li, Gongqing Zhang, Zhixin Qiao, Min He, Xuanlin Wang, Yu Wang, Xingwei Jiang, Lihua Su, Yuezhong He, Suping Ren, Qun Yu
A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27906092/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#9
Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac, Markus A Rüegg
BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively...
March 21, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905989/the-histone-deacetylase-inhibitor-sodium-butyrate-exhibits-neuroprotective-effects-for-ischemic-stroke-in-middle-aged-female-rats
#10
Min Jung Park, Farida Sohrabji
BACKGROUND: Sodium butyrate (NaB) is a histone deacetylase (HDAC) inhibitor exhibiting anti-inflammatory and neuroprotective effects in a rat ischemic model of stroke as well as a myocardial ischemia model. Although clinical evidence shows that older women are at higher risk for stroke occurrence and greater stroke severity, no studies have evaluated the effectiveness of NaB either in females or in older animals. METHODS: To determine the effects of NaB on stroke in older females, acyclic middle-aged Sprague-Dawley female rats (9-11 months old, constant diestrus) were subject to middle cerebral artery occlusion (MCAo) by intracerebral injection of recombinant endothelin-1...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27904737/a-clinical-update-on-the-role-of-carfilzomib-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#11
REVIEW
B Franken, N W C J van de Donk, J C Cloos, S Zweegman, H M Lokhorst
Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904654/augmentation-of-histone-deacetylase-3-hdac3-epigenetic-signature-at-the-interface-of-proinflammation-and-insulin-resistance-in-patients-with-type-2-diabetes
#12
Chandrakumar Sathishkumar, Paramasivam Prabu, Mahalingam Balakumar, Raji Lenin, Durai Prabhu, Ranjith Mohan Anjana, Viswanathan Mohan, Muthuswamy Balasubramanyam
BACKGROUND: A role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27902771/piceatannol-attenuates-renal-fibrosis-induced-by-unilateral-ureteral-obstruction-via-downregulation-of-histone-deacetylase-4-5-or-p38-mapk-signaling
#13
Sin Young Choi, Zhe Hao Piao, Li Jin, Jung Ha Kim, Gwi Ran Kim, Yuhee Ryu, Ming Quan Lin, Hyung-Seok Kim, Hae Jin Kee, Myung Ho Jeong
Piceatannol, a resveratrol metabolite, is a phenolic compound found in red wine and grapes. We investigated the effect of piceatannol on renal fibrosis and histone deacetylase (HDAC) expression in a mouse model of unilateral ureteral obstruction (UUO). Fibrosis was established by UUO and piceatannol was intraperitoneally injected for 2 weeks. Piceatannol suppressed extracellular matrix (ECM) protein deposition including collagen type I and fibronectin as well as connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in UUO kidneys...
2016: PloS One
https://www.readbyqxmd.com/read/27901066/greater-efficacy-of-atorvastatin-versus-a-non-statin-lipid-lowering-agent-against-renal-injury-potential-role-as-a-histone-deacetylase-inhibitor
#14
Ravi Shankar Singh, Dharmendra Kumar Chaudhary, Aradhana Mohan, Praveen Kumar, Chandra Prakash Chaturvedi, Carolyn M Ecelbarger, Madan M Godbole, Swasti Tiwari
Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors have been shown to improve diabetic nephropathy. However, whether they provide protection via Histone deacetylases (HDAC) inhibition is not clear. We conducted a comparative evaluation of Atorvastatin (AT) versus the non-statin cholesterol-lowering drug, Ezetimibe (EZT) on severity of diabetic nephropathy. Streptozotocin-treated male Wistar rats were fed a cholesterol-supplemented diet and gavaged daily with vehicle, AT or EZT. Control rats received normal diet and gavaged vehicle (n = 8-9/group)...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900262/impaired-histone-deacetylases-5-and-6-expression-mimics-the-effects-of-obesity-and-hypoxia-on-adipocyte-function
#15
Julien Bricambert, Dimitri Favre, Saška Brajkovic, Amélie Bonnefond, Raphael Boutry, Roberto Salvi, Valérie Plaisance, Mohamed Chikri, Giulia Chinetti-Gbaguidi, Bart Staels, Vittorio Giusti, Robert Caiazzo, François Pattou, Gérard Waeber, Philippe Froguel, Amar Abderrahmani
OBJECTIVE: The goal of the study was to investigate the role of histone deacetylases (HDACs) in adipocyte function associated with obesity and hypoxia. METHODS: Total proteins and RNA were prepared from human visceral adipose tissues (VAT) of human obese and normal weight subjects and from white adipose tissue (WAT) of C57Bl6-Rj mice fed a normal or high fat diet (HFD) for 16 weeks. HDAC activity was measured by colorimetric assay whereas the gene and protein expression were monitored by real-time PCR and by western blotting, respectively...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27897114/ureas-applications-in-drug-design-and-development
#16
Ajit Dhananjay Jagtap, Nagendra Bharatrao Kondekar, Amit A Sadani, Ji-Wang Chern
The unique hydrogen binding capabilities of ureas make them an important functional group to make drug-target interactions and thus incorporated in small molecules displaying broad range of bioactivities. The related research and numerous excellent achievements of ureas applicability in drug design for the modulation of selectivity, stability, toxicity and pharmacokinetic profile of lead molecules have become active topic. This review aims to provide insights in to the significance of urea in drug design by summarizing successful studies of various urea derivatives as modulators biological targets (viz...
November 29, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27890930/histone-deacetylase-inhibitors-interrupt-hsp90-rasgrp1-and-hsp90-craf-interactions-to-upregulate-bim-and-circumvent-drug-resistance-in-lymphoma-cells
#17
H Ding, K L Peterson, C Correia, B Koh, P A Schneider, G S Nowakowski, S H Kaufmann
Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of cutaneous T cell lymphoma and multiple myeloma, are undergoing evaluation in other lymphoid neoplasms. How they kill susceptible cells is incompletely understood. Here we show that trichostatin A, romidepsin, and panobinostat induce apoptosis across a panel of malignant B cell lines, including lines that are intrinsically resistant to bortezomib, etoposide, cytarabine, and BH3 mimetics. Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased acetylation of the chaperone heat shock protein 90 (HSP90), causing release and degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to downregulation of mitogen activated protein kinase pathway signaling and upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890617/polycistronic-trna-and-crispr-guide-rna-enables-highly-efficient-multiplexed-genome-engineering-in-human-cells
#18
Fengping Dong, Kabin Xie, Yueying Chen, Yinong Yang, Yingwei Mao
CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides a potential tool to introduce multiple mutations in a genome. To mimic complicated genomic events in human diseases, such as multiple gene deletions or mutations, two or more small guide RNAs (sgRNA) must be introduced all together. This can be achieved by separate Pol III promoters in a construct. However, limited enzyme sites and the increased insertion size lower the efficiency to make a construct...
November 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27889835/valproic-acid-reduces-hair-loss-and-improves-survival-in-patients-receiving-temozolomide-based-radiation-therapy-for-high-grade-glioma
#19
Shinichi Watanabe, Yui Kuwabara, Satoshi Suehiro, Daisuke Yamashita, Mamoru Tanaka, Akihiro Tanaka, Shiro Ohue, Hiroaki Araki
PURPOSE: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma...
November 26, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27889685/a-naturally-occurring-mixture-of-tocotrienols-inhibits-the-growth-of-human-prostate-tumor-associated-with-epigenetic-modifications-of-cyclin-dependent-kinase-inhibitors-p21-and-p27
#20
Ying Huang, Renyi Wu, Zheng-Yuan Su, Yue Guo, Xi Zheng, Chung S Yang, Ah-Ng Kong
Tocotrienols, members of the vitamin E family, have three unsaturated bonds in their side chains. Recently, it has been suggested that the biological effects of tocotrienols may differ from that of tocopherols. Several in vitro studies have shown that tocotrienols have stronger anticancer effects than tocopherols. VCaP cell line used in this study is from a vertebral bone metastasis from a patient with prostate cancer. Eight-week-old male NCr(-/-) nude mice were subcutaneously injected with VCaP-luc cells in matrigel and then administered a tocotrienol mixture for 8 weeks...
November 4, 2016: Journal of Nutritional Biochemistry
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