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Histone deacetylase

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https://www.readbyqxmd.com/read/28110187/insecticidal-activities-of-histone-deacetylase-inhibitors-against-a-dipteran-parasite-of-sheep-lucilia-cuprina
#1
Neil H Bagnall, Barney M Hines, Andrew J Lucke, Praveer K Gupta, Robert C Reid, David P Fairlie, Andrew C Kotze
Histone deacetylase inhibitors (HDACi) are being investigated for the control of various human parasites. Here we investigate their potential as insecticides for the control of a major ecto-parasite of sheep, the Australian sheep blowfly, Lucilia cuprina. We assessed the ability of HDACi from various chemical classes to inhibit the development of blowfly larvae in vitro, and to inhibit HDAC activity in nuclear protein extracts prepared from blowfly eggs. The HDACi prodrug romidepsin, a cyclic depsipeptide that forms a thiolate, was the most potent inhibitor of larval growth, with equivalent or greater potency than three commercial blowfly insecticides...
January 10, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28109694/sirt1-as-a-potential-biomarker-of-response-to-treatment-with-glatiramer-acetate-in-multiple-sclerosis
#2
Daniel Hewes, Alexandru Tatomir, Adam M Kruszewski, Gautam Rao, Cosmin A Tegla, Jonathan Ciriello, Vingh Nguyen, Walter Royal, Christopher Bever, Violeta Rus, Horea Rus
SIRT1, a NAD dependent histone and protein deacetylase, is a member of the histone deacetylase class III family. We previously showed that SIRT1 mRNA expression is significantly lower in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. We have now investigated SIRT1 as a possible biomarker to predict relapse as well as responsiveness to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2years, a cohort of 15 GA-treated RRMS patients were clinically monitored using the Expanded Disability Status Scale and assessed for MS relapses...
January 18, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28109246/sensitivity-of-osteosarcoma-cells-to-hdac-inhibitor-ar-42-mediated-apoptosis
#3
Sridhar Murahari, Aimee L Jalkanen, Samuel K Kulp, Ching-Shih Chen, Jaime F Modiano, Cheryl A London, William C Kisseberth
BACKGROUND: Osteosarcoma (OS) is the most common primary bone tumor in both humans and dogs and is the second leading cause of cancer related deaths in children and young adults. Limb sparing surgery along with chemotherapy has been the mainstay of treatment for OS. Many patients are not cured with current therapies, presenting a real need for developing new treatments. Histone deacetylase (HDAC) inhibitors are a promising new class of anticancer agents. In this study, we investigated the activity of the novel HDAC inhibitor AR-42 in a panel of human and canine OS cell lines...
January 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28109165/melatonin-and-sirtuins-a-not-so-unexpected-relationship
#4
Juan C Mayo, Rosa M Sainz, Pedro González Menéndez, Vanesa Cepas, Dun-Xian Tan, Russel J Reiter
Epigenetic modifications, including methylation or acetylation as well as posttranscriptional modifications are mechanisms used by eukaryotic cells to increase the genome diversity in terms of differential gene expression and protein diversity. Among these modifying enzymes, sirtuins, a class III histone deacetylase (HDAC) enzymes are of particular importance. Sirtuins regulate the cell cycle, DNA repair, cell survival and apoptosis, thus having important roles in normal and cancer cells. Sirtuins can also regulate metabolic pathways by changing preference for glycolysis under aerobic conditions as well as glutaminolysis...
January 21, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28109123/sodium-butyrate-protects-against-high-fat-diet-induced-cardiac-dysfunction-and-metabolic-disorders-in-type-ii-diabetic-mice
#5
Ling Zhang, Jianfeng Du, Naohiro Yano, Hao Wang, Yu Tina Zhao, Dubielecka-Szczerba Patricia, Shougang Zhuang, Eugene Y Chin, Gangjian Qin, Ting C Zhao
Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in type II diabetes and obesity remains unknown. Here we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively...
January 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28108589/chromatin-regulation-by-the-nua4-acetyltransferase-complex-is-mediated-by-essential-interactions-between-enhancer-of-polycomb-epl1-and-esa1
#6
Naomi E Searle, Ana Lilia Torres-Machorro, Lorraine Pillus
Enzymes that modify and remodel chromatin act in broadly conserved macromolecular complexes. One key modification is the dynamic acetylation of histones and other chromatin proteins by opposing activities of acetyltransferase and deacetylase complexes. Among acetyltransferases, the NuA4 complex containing Tip60 or its Saccharomyces cerevisiae ortholog, Esa1, is of particular significance because of its roles in crucial genomic processes including DNA damage repair and transcription. The catalytic subunit Esa1 is essential, as are five non-catalytic NuA4 subunits...
January 20, 2017: Genetics
https://www.readbyqxmd.com/read/28108250/synthesis-of-vorinostat-and-cholesterol-conjugate-to-enhance-the-cancer-cell-uptake-selectivity
#7
Nethrie D Idippily, Chunfang Gan, Paul Orefice, Jane Peterson, Bin Su
Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28107769/the-transcriptional-modulator-ifrd1-controls-pgc-1%C3%AE-expression-under-short-term-adrenergic-stimulation-in-brown-adipocytes
#8
Gyujin Park, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Yukari Nakamura, Yukio Yoneda, Takeshi Takarada, Eiichi Hinoi
Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in the brown adipose tissue, and inducible brown adipocytes (so-called beige adipocytes), which sporadically reside within the white adipose tissue. Here we identified the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative regulator of thermogenic and mitochondrial gene expression in brown adipocytes. Ifrd1 expression was markedly induced by cold exposure and administration of CL-316243 (a β3 adrenergic agonist) in interscapular brown adipose and inguinal subcutaneous white adipose tissues, but not in epididymal visceral white adipose tissue, in vivo...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107750/effect-of-clinically-approved-hdac-inhibitors-on-plasmodium-leishmania-and-schistosoma-parasite-growth
#9
Ming Jang Chua, Megan S J Arnold, Weijun Xu, Julien Lancelot, Suzanne Lamotte, Gerald F Späth, Eric Prina, Raymond J Pierce, David P Fairlie, Tina S Skinner-Adams, Katherine T Andrews
Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L...
December 23, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28107582/immunoexpression-of-hdac1-hdac2-and-hat1-in-actinic-cheilitis-and-lip-squamous-cell-carcinoma
#10
Emanuely da Silva Chrun, Filipe Modolo, Daniella Serafim Couto Vieira, Álvaro Luiz Socorro Borges, Renata Goulart Castro, Filipe Ivan Daniel
BACKGROUND: Acetylation/deacetylation are the most studied covalent histone modifications resulting in transcriptional regulation with histone deacetylases (HDAC) and histone acetyltransferases (HAT) as the main associated enzymes. These enzymes overexpression induces abnormal transcription of key genes that regulate important cellular functions, such as proliferation, cell cycle regulation, and apoptosis. Thus, the expression of different HATs and HDACs has been evaluated in various cancers...
January 20, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28107195/a-new-hdac-inhibitor-cinnamoylphenazine-shows-antitumor-activity-in-association-with-intensive-macropinocytosis
#11
Bing-Yan Zhu, Bo-Yang Shang, Yue Du, Yi Li, Liang Li, Xian-Dong Xu, Yong-Su Zhen
Previous studies have shown that intensive macropinocytosis occurs in cancer cells and neutral red (NR) is noted for its capability to enter into the cell massively through a process mimetic to macropinocytosis. In addition, trans-cinnamic acid (tCA) has been found to be an inhibitor of histone deacetylase (HDAC). In the present study, cinnamoylphenazine (CA-PZ) that consists of NR and tCA moieties was synthesized and evaluated. As shown, CA-PZ massively entered into colon carcinoma HT-29 cells and pancreatic carcinoma MIA PaCa-2 cells and this entry was blocked by 5-(N-ethyl-N-isopropyl) amiloride (EIPA, an inhibitor of macropinocytosis), indicating a macropinocytosis-mediated uptake...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106794/a-thoroughly-validated-virtual-screening-strategy-for-discovery-of-novel-hdac3-inhibitors
#12
Huabin Hu, Jie Xia, Dongmei Wang, Xiang Simon Wang, Song Wu
Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28103771/structure-based-study-of-natural-products-with-anti-schistosoma-activity
#13
Ibezim Akachukwu, Olujide Oludayo Olubiyi, Ata Kosisochukwu, Mbah Chika John, Nwodo Ngozi Justina
: Background Schistosomiasis is a parasitic protozoal disease caused by flatworms of the genus Schistosoma. Although the disease threatens millions of lives, it is still at the top list of neglected tropical diseases and praziquantel, the only common schistosocidal drug in use, has records of decreasing efficiency and cases of resistance. Also, reports revealed that people in the rural areas, who are most affected, rely mostly on traditional herbal medicines because of limited access to modern healthcare...
January 19, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28103535/down-regulation-of-histone-deacetylase-4-5-and-6-as-a-mechanism-of-synergistic-enhancement-of-apoptosis-in-human-lung-cancer-cells-treated-with-the-combination-of-a-synthetic-retinoid-am80-and-green-tea-catechin
#14
Yukiko Oya, Anupom Mondal, Anchalee Rawangkan, Sonthaya Umsumarng, Keisuke Iida, Tatsuro Watanabe, Miki Kanno, Kaori Suzuki, Zhenghao Li, Hiroyuki Kagechika, Koichi Shudo, Hirota Fujiki, Masami Suganuma
(-)-Epigallocatechin gallate (EGCG), a green tea catechin, acts as a synergist with various anticancer drugs, including retinoids. Am80 is a synthetic retinoid with a different structure from all-trans-retinoic acid: Am80 is now clinically utilized as a new drug for relapsed and intractable acute promyelocytic leukemia patients. Our experiments showed that the combination of EGCG and Am80 synergistically induced both apoptosis in human lung cancer cell line PC-9 and up-regulated expressions of growth arrest and DNA damage-inducible gene 153 (GADD153), death receptor 5, and p21(waf1) genes in the cells...
January 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28102966/histone-deacetylase-2-is-decreased-in-peripheral-blood-pro-inflammatory-cd8-t-and-nkt-like-lymphocytes-following-lung-transplant
#15
Greg Hodge, Sandra Hodge, Chien-Li Holmes-Liew, Paul N Reynolds, Mark Holmes
BACKGROUND AND OBJECTIVE: Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown...
February 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28102705/the-acetyl-code-in-rheumatoid-arthritis-and-other-rheumatic-diseases
#16
Chiara Angiolilli, Dominique L Baeten, Timothy R Radstake, Kris A Reedquist
Growing evidence supports the idea that aberrancies in epigenetic processes contribute to the onset and progression of human immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Epigenetic regulators of histone tail modifications play a role in chromatin accessibility and transcriptional responses to inflammatory stimuli. Among these, histone deacetylases (HDACs) regulate the acetylation status of histones and nonhistone proteins, essential for immune responses. Broad-spectrum HDAC inhibitors are well-known anti-inflammatory agents and reduce disease severity in animal models of arthritis; however, selective HDAC inhibitors remain poorly studied...
January 19, 2017: Epigenomics
https://www.readbyqxmd.com/read/28102109/epigenetic-regulation-of-rgs2-regulator-of-g-protein-signaling-2-in-chemoresistant-ovarian-cancer-cells
#17
Ercan Cacan
Regulator of G-protein signaling 2 (RGS2) is a GTPase-activating protein functioning as an inhibitor of G-protein coupled receptors (GPCRs). RGS2 dysregulation was implicated in solid tumour development and RGS2 downregulation has been reported in prostate and ovarian cancer progression. However, the molecular mechanism by which RGS2 expression is suppressed in ovarian cancer remains unknown. The expression and epigenetic regulation of RGS2 in chemosensitive and chemoresistant ovarian cancer cells were determined by qRT-PCR and chromatin immunoprecipitation assays, respectively...
January 19, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28101176/anticancer-effects-of-valproic-acid-on-oral-squamous-cell-carcinoma-via-sumoylation-in-vivo-and-in-vitro
#18
Zhijian Sang, Yang Sun, Hong Ruan, Yong Cheng, Xiaojun Ding, Youcheng Yu
Aberrant histone deacetylase (HDAC) has a key role in the neoplastic process associated with the epigenetic patterns of tumor-related genes. The present study was performed to investigate the effects and determine the mechanism of action of the HDAC inhibitor, valproic acid (VPA), on the CAL27 cell line derived from oral squamous cell carcinoma (OSCC). The effects of VPA on the viability of CAL27 cells were investigated using MTT assays. Alterations in the cell cycle and apoptosis were also examined using propidium iodide (PI) and Annexin V-PI assays, and were subequently analyzed by flow cytometry...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100513/loss-of-ranbp2-in-motor-neurons-causes-the-disruption-of-nucleocytoplasmic-and-chemokine-signaling-and-proteostasis-of-hnrnph3-and-mmp28-and-the-development-of-amyotrophic-lateral-sclerosis-als-like-syndromes
#19
Kyoung-In Cho, Dosuk Yoon, Sunny Qiu, Zachary Danziger, Warren M Grill, William C Wetsel, Paulo A Ferreira
The pathogenic drivers of sporadic and familial motor neuron disease (MND), such ALS, are unknown. MND impair the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-effect mechanisms of Ran GTPase modulators in motoneuron pathobiology are heretofore elusive. The cytosolic and peripheral nucleoporin, Ranbp2, is a critical regulator of the Ran GTPase cycle and proteostasis of neurological disease-prone substrates, but the roles of Ranbp2 in motoneuron biology and disease remain unknown...
January 18, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28100329/-protective-effect-of-histone-acetylation-against-cortical-injury-in-neonatal-rats
#20
Ji-Chong Huang, Ya-Fei Li, Feng-Yan Zhao, Yi Qu, De-Zhi Mu
OBJECTIVE: To investigate the protective effect of histone acetylation against hypoxic-ischemic cortical injury in neonatal rats. METHODS: A total of 90 neonatal rats aged 3 days were divided into three groups: sham-operation, cortical injury model, and sodium butyrate (a histone deacetylase inhibitor) treatment. The rats in the model and the sodium butyrate treatment groups were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg), and then right common carotid artery ligation was performed 2 hours later and the rats were put in a hypoxic chamber (oxygen concentration 6...
January 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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