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Histone deacetylase inhibitor

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https://www.readbyqxmd.com/read/28935977/zebrafish-in-vivo-screening-for-compounds-amplifying-hematopoietic-stem-and-progenitor-cells-preclinical-validation-in-human-cd34-stem-and-progenitor-cells
#1
Guruchandar Arulmozhivarman, Martin Kräter, Manja Wobus, Jens Friedrichs, Elham Pishali Bejestani, Katrin Müller, Katrin Lambert, Dimitra Alexopoulou, Andreas Dahl, Martin Stöter, Marc Bickle, Nona Shayegi, Jochen Hampe, Friedrich Stölzel, Michael Brand, Malte von Bonin, Martin Bornhäuser
The identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935884/muscle-hypertrophy-in-hypoxia-with-inflammation-is-controlled-by-bromodomain-and-extra-terminal-domain-proteins
#2
Clovis Chabert, Saadi Khochbin, Sophie Rousseaux, Rebecca Furze, Nicholas Smithers, Rab Prinjha, Uwe Schlattner, Christophe Pison, Hervé Dubouchaud
Some of the Chronic Obstructive Pulmonary Disease (COPD) patients engaged in exercise-based muscle rehabilitation programs are unresponsive. To unravel the respective role of chronic hypoxia and pulmonary inflammation on soleus muscle hypertrophic capacities, we challenged male Wistar rats to repeated lipopolysaccharide instillations, associated or not with a chronic hypoxia exposure. Muscle hypertrophy was initiated by bilateral ablation of soleus agonists 1 week before sacrifice. To understand the role played by the histone acetylation, we also treated our animals with an inhibitor of bromodomains and extra terminal proteins (I-BET) during the week after surgery...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28933264/from-a-better-understanding-of-the-mechanisms-of-action-of-histone-deacetylases-inhibitors-to-the-progress-of-the-treatment-of-malignant-lymphomas-and-plasma-cell-myeloma
#3
Romeo-Gabriel Mihăilă
BACKGROUND: Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. OBJECTIVE: Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. METHOD: A minireview was achieved using the articles published in PubMed in the last two years and the new patents made in this field...
September 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28932910/a-histone-deacetylase-gene-slhda3-acts-as-a-negative-regulator-of-fruit-ripening-and-carotenoid-accumulation
#4
Jun-E Guo, Zongli Hu, Xiaohui Yu, Anzhou Li, Fenfen Li, Yunshu Wang, Shibing Tian, Guoping Chen
SlHDA3 functions as an inhibitor and regulates tomato fruit ripening and carotenoid accumulation. Post-translational modifications, including histones acetylation, play a pivotal role in the changes of chromatin structure dynamic modulation and gene activity. The regulation of histone acetylation is achieved by the action of histone acetyltransferases and deacetylases, which play crucial roles in the regulation of transcription activation. There is an increasing research focus on histone deacetylation in crops, but the role of histone deacetylase genes (HDACs) in tomato has not been elucidated...
September 20, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28932644/romidepsin-alone-or-in-combination-with-anti-cd20-chimeric-antigen-receptor-expanded-natural-killer-cells-targeting-burkitt-lymphoma-in-vitro-and-in-immunodeficient-mice
#5
Yaya Chu, Ashlin Yahr, Brian Huang, Janet Ayello, Matthew Barth, Mitchell S Cairo
Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28930559/histone-deacetylase-a-potential-therapeutic-target-for-ovarian-dysfunction
#6
Sunita Sunita, Pankaj Kumar Singh, Suneel Kumar Onteru, Dheer Singh
Post-partum uterine disorders and reproductive tract infections cause ovarian dysfunction and infertility. Histone deacetylases (HDACs) prevent the relaxation of chromatin, and positively or negatively regulate transcription. Hence, HDACs play a pivotal role in altering the gene expression that impact different signalling pathways underling ovarian dysfunction. Thus, HDAC inhibitors (HDACi) may act as potential therapeutic targets in the treatment of an array of disorders impacting ovarian function.
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28929430/new-drugs-in-the-pipeline-for-the-treatment-of-hiv-a-review
#7
REVIEW
Leigh Anne Hylton Gravatt, Crystal R Leibrand, Sulay Patel, MaryPeace McRae
PURPOSE OF REVIEW: The purpose of this paper is to review therapies with new mechanisms of action for the treatment of HIV that are at least in phase 2 clinical trials. RECENT FINDINGS: There are several new mechanisms of action being represented within clinical development, including histone deacetylase (HDAC) inhibitors, gene therapies, broadly neutralizing anti-HIV antibodies, immune modulation, and drugs with new mechanisms to block HIV entry. The new therapies are being developed for both as add-on therapy to existing combination antiretroviral therapy and as agents to be used during treatment interruption...
September 19, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28929094/gestational-age-dependent-increase-of-survival-motor-neuron-protein-in-umbilical-cord-derived-mesenchymal-stem-cells
#8
Sota Iwatani, Nur Imma Fatimah Harahap, Dian Kesumapramudya Nurputra, Shinya Tairaku, Akemi Shono, Daisuke Kurokawa, Keiji Yamana, Khin Kyae Mon Thwin, Makiko Yoshida, Masami Mizobuchi, Tsubasa Koda, Kazumichi Fujioka, Mariko Taniguchi-Ikeda, Hideto Yamada, Ichiro Morioka, Kazumoto Iijima, Hisahide Nishio, Noriyuki Nishimura
BACKGROUND: Spinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt symptoms...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28928749/foxo1-regulates-bacteria-induced-neutrophil-activity
#9
Guangyu Dong, Liang Song, Chen Tian, Yu Wang, Fang Miao, Jiabao Zheng, Chanyi Lu, Sarah Alsadun, Dana T Graves
Neutrophils play an essential role in the innate immune response to microbial infection and are particularly important in clearing bacterial infection. We investigated the role of the transcription factor FOXO1 in the response of neutrophils to bacterial challenge with Porphyromonas gingivalis in vivo and in vitro. In these experiments, the effect of lineage-specific FOXO1 deletion in LyzM.Cre(+)FOXO1(L/L) mice was compared with matched littermate controls. FOXO1 deletion negatively affected several critical aspects of neutrophil function in vivo including mobilization of neutrophils from the bone marrow (BM) to the vasculature, recruitment of neutrophils to sites of bacterial inoculation, and clearance of bacteria...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928640/hdac3-inhibitor-rgfp966-modulates-neuronal-memory-for-vocal-communication-signals-in-a-songbird-model
#10
Mimi L Phan, Mark M Gergues, Shafali Mahidadia, Jorge Jimenez-Castillo, David S Vicario, Kasia M Bieszczad
Epigenetic mechanisms that modify chromatin conformation have recently been under investigation for their contributions to learning and the formation of memory. For example, the role of enzymes involved in histone acetylation are studied in the formation of long-lasting memories because memory consolidation requires gene expression events that are facilitated by an open state of chromatin. We recently proposed that epigenetic events may control the entry of specific sensory features into long-term memory by enabling transcription-mediated neuronal plasticity in sensory brain areas...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28928414/disruption-to-schizophrenia-associated-gene-fez1-in-the-hippocampus-of-hdac11-knockout-mice
#11
Dale T Bryant, Christian Landles, Aikaterini S Papadopoulou, Agnesska C Benjamin, Joshua K Duckworth, Thomas Rosahl, Caroline L Benn, Gillian P Bates
Histone Deacetylase 11 (HDAC11) is highly expressed in the central nervous system where it has been reported to have roles in neural differentiation. In contrast with previous studies showing nuclear and cytoplasmic localisation, we observed synaptic enrichment of HDAC11. Knockout mouse models for HDACs 1-9 have been important for guiding the development of isoform specific HDAC inhibitors as effective therapeutics. Given the close relationship between HDAC11 and neural cells in vitro, we examined neural tissue in a previously uncharacterised Hdac11 knockout mouse (Hdac11 (KO/KO))...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928236/histone-deacetylase-inhibition-ameliorates-hypertension-and-hyperglycemia-in-a-model-of-cushing-s-syndrome
#12
Hae-Ahm Lee, Seol-Hee Kang, Mina Kim, Eunjo Lee, Hyun-Min Cho, Eun-Kyung Moon, Inkyeom Kim
Cushing's syndrome (CS) caused by hypercortisolism is occasionally accompanied by metabolic disorders such as hypertension, diabetes mellitus (DM), dyslipidemia and central obesity. Thus, morbidity and mortality, observed in cardiovascular disease, are elevated in patients with CS. We hypothesized that HDAC inhibition (HDACi) decreased transcriptional activity of glucocorticoid receptor (GR), which ameliorates hypertension and hyperglycemia in patients with CS. To establish an animal model of hypercortisolism, Sprague-Dawley rats were infused with adrenocorticotropic hormone (ACTH, 40 ng/day) or dexamethasone (Dex, 10 μg/day) via osmotic minipumps for 4 weeks...
September 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28928030/the-histone-deacetylase-inhibitor-sodium-butyrate-protects-against-noise-induced-hearing-loss-in-guinea-pigs
#13
Deng-Hua Yang, Jing Xie, Ke Liu, Zhe Peng, Jing-Ying Guo, Shu-Kui Yu, Guo-Peng Wang, Shu-Sheng Gong
Noise-induced hearing loss (NIHL) severely impacts the quality of life of affected individuals. Oxidative stress resulting from noise exposure is a significant cause of NIHL. Although histone deacetylase (HDAC) inhibitors were shown to protect against NIHL, the underlying mechanism remains unclear, and it is not known how they act on noise-induced oxidative stress. In the current study, we investigated the expression levels of acetyl-histone H3 (Lys9) (H3-AcK9), histone deacetylase 1 (HDAC1), and 3-nitrotyrosine (3-NT), an oxidative stress marker, in a guinea pig model of NIHL using immunohistology and Western blotting...
September 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28925883/novel-therapeutics-in-glaucoma-management
#14
Claudio Bucolo, Chiara Bianca Maria Platania, Filippo Drago, Michele Reibaldi, Vincenza Bonfiglio, Teresio Avitabile, Maurizio Uva
Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell death and alterations of visual field. Elevated intraocular pressure (IOP) is considered the main risk factor of glaucoma, even though other factors cannot be ruled out, such as epigenetic mechanisms. An overview of the ultimate promising experimental drugs to manage glaucoma has been provided. In particular, we have focused on purinergic ligands, KATP channel activators, gases (nitric oxide, carbon monoxide and hydrogen sulfide), non-glucocorticoid steroidal compounds, neurotrophic factors, PI3K/Akt activators, citicoline, histone deacetylase inhibitors, cannabinoids, dopamine and serotonin receptors ligands, small interference RNA, and Rho kinase inhibitors...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28923385/targeting-breast-cancer-stem-cells-by-novel-hdac3-selective-inhibitors
#15
Hao-Yu Hsieh, Hsiao-Ching Chuang, Fang-Hsiu Shen, Kinjal Detroja, Ling-Wei Hsin, Ching-Shih Chen
Although histone deacetylase (HDAC) inhibitors have been known to suppress the cancer stem cell (CSC) population in multiple types of cancer cells, it remains unclear which HDAC isoforms and corresponding mechanisms contribute to this anti-CSC activity. Pursuant to our previous finding that HDAC8 regulates CSCs in triple-negative breast cancer (TNBC) cells by targeting Notch1 stability, we investigated related pathways and found HDAC3 to be mechanistically linked to CSC homeostasis by increasing β-catenin expression through the Akt/GSK3β pathway...
September 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28921466/roles-of-hdacs-in-the-responses-of-innate-immune-cells-and-as-targets-in-inflammatory-diseases
#16
Yiqun Hu, Bandar Ali Suliman
Histone deacetylases (HDACs) are an emerging class of molecules involved in the epigenetic regulation of innate immune responses through Toll-like receptor (TLR) and interferon (IFN) signaling pathways. HDACs are also key drivers of inflammatory diseases via epigenetic regulation through chromatin DNA and histone modification by methylation and acetylation, among other mechanisms, which control innate immune cell gene expression. Importantly, these epigenetic changes are reversible, and HDACs may also be targeted by small-molecule HDAC inhibitors, which have been used in clinical settings for cancer therapy...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28919994/effect-of-entinostat-on-nk-cell-mediated-cytotoxicity-against-osteosarcoma-cells-and-osteosarcoma-lung-metastasis
#17
Simin Kiany, Gangxiong Huang, Eugenie S Kleinerman
There is a crucial need for a new therapeutic approach for osteosarcoma (OS) lung metastasis since this disease remains the main cause of mortality in OS. We previously demonstrated that natural killer (NK) cell therapy has minimal efficacy against OS metastasis. This study determined whether the histone deacetylase inhibitor entinostat could immunosensitize OS cells to NK cell lysis and increases the efficacy of NK cell therapy for OS lung metastasis. Entinostat upregulated ligands for NK cell-activating receptors (major histocompatibility complex [MHC] class I polypeptide-related chain A [MICA] and B [MICB]; UL16 binding proteins 1, 2, 5, and 6; and CD155) on OS cells both in vitro and in vivo and led to more susceptibility to NK cell-mediated cytotoxicity in vitro...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28918353/antitumor-platinum-iv-derivatives-of-carboplatin-and-the-histone-deacetylase-inhibitor-4-phenylbutyric-acid
#18
Awatif Rashed Z Almotairy, Valentina Gandin, Liam Morrison, Cristina Marzano, Diego Montagner, Andrea Erxleben
Five new platinum(IV) derivatives of carboplatin each incorporating the histone deacetylase inhibitor 4-phenylbutyrate in axial position were synthesized and characterized by (1)H and (195)Pt NMR spectroscopy, electrospray ionization mass spectrometry and elemental analysis, namely cis,trans-[Pt(CBDCA)(NH3)2(PBA)(OH)] (1), cis,trans-[Pt(CBDCA)(NH3)2(PBA)2] (2), cis,trans-[Pt(CBDCA)(NH3)2(PBA)(bz)] (3), cis,trans-[Pt(CBDCA)(NH3)2(PBA)(suc)] (4) and cis,trans-[Pt(CBDCA)(NH3)2)(PBA)(ac)] (5) (PBA=4-phenylbutyrate, CBDCA=1,1-cyclobutane dicarboxylate, bz=benzoate, suc=succinate and ac=acetate)...
September 10, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28916721/loss-of-cardiac-carnitine-palmitoyltransferase-2-results-in-rapamycin-resistant-acetylation-independent-hypertrophy
#19
Andrea S Pereyra, Like Y Hasek, Kate L Harris, Alycia G Berman, Frederick W Damen, Craig J Goergen, Jessica M Ellis
Cardiac hypertrophy is closely linked to impaired fatty acid oxidation, but the molecular basis of this link is unclear. Here, we investigated the loss of an obligate enzyme in mitochondrial long-chain fatty acid oxidation, carnitine palmitoyltransferase 2 (CPT2), on muscle and heart structure, function, and molecular signatures in a muscle- and heart-specific CPT2-deficient mouse (Cpt2M-/-) model. CPT2 loss in heart and muscle reduced complete oxidation of long-chain fatty acids by 87% and 69%, respectively, without altering body weight, energy expenditure, respiratory quotient, or adiposity...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916629/histone-deacetylase-inhibition-induces-odor-preference-memory-extension-and-maintains-enhanced-ampa-receptor-expression-in-the-rat-pup-model
#20
Sriya Bhattacharya, Bandhan Mukherjee, Jules J E Doré, Qi Yuan, Carolyn W Harley, John H McLean
Histone deacetylase (HDAC) plays a role in synaptic plasticity and long-term memory formation. We hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that have been hypothesized to support memory. We used an early odor preference learning model in neonate rat pups that normally produces only 24-h memory to test behavior and examine receptor protein expression. Our behavioral studies showed that intrabulbar infusion of TSA, prior to pairing of the conditioned stimulus (peppermint odor) with the unconditioned stimulus (tactile stimulation), prolonged 24-h odor preference memory for at least 9 d...
October 2017: Learning & Memory
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