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https://www.readbyqxmd.com/read/29785087/transcriptomic-impacts-of-rumen-epithelium-induced-by-butyrate-infusion-in-dairy-cattle-in-dry-period
#1
Ransom L Baldwin, Robert W Li, Yankai Jia, Cong-Jun Li
The purpose of this study was to evaluate the effects of butyrate infusion on rumen epithelial transcriptome. Next-generation sequencing (NGS) and bioinformatics are used to accelerate our understanding of regulation in rumen epithelial transcriptome of cattle in the dry period induced by butyrate infusion at the level of the whole transcriptome. Butyrate, as an essential element of nutrients, is a histone deacetylase (HDAC) inhibitor that can alter histone acetylation and methylation, and plays a prominent role in regulating genomic activities influencing rumen nutrition utilization and function...
2018: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/29778718/nimbolide-epigenetically-regulates-autophagy-and-apoptosis-in-breast-cancer
#2
Venkatesh Pooladanda, Soumya Bandi, Sandhya Rani Mondi, Krishna Mohan Gottumukkala, Chandraiah Godugu
Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29774413/alterations-in-histone-acetylation-following-exposure-to-60-co-%C3%AE-rays-and-their-relationship-with-chromosome-damage-in-human-lymphoblastoid-cells
#3
Xue-Lei Tian, Xue Lu, Jiang-Bin Feng, Tian-Jing Cai, Shuang Li, Mei Tian, Qing-Jie Liu
Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0-2 Gy 60 Co γ-rays...
May 17, 2018: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/29772299/biophenols-enzymes-%C3%AE-secretase-cholinesterases-histone-deacetylase-and-tyrosinase-inhibitors-from-olive-olea-europaea-l
#4
Syed Haris Omar, Christopher J Scott, Adam S Hamlin, Hassan K Obied
The focus of this study was on inhibition of enzymes involved in the pathogenesis Alzheimer's disease (AD) including prime amyloid beta (Aβ) producing enzyme (β-secretase: BACE-1) and disease progression enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), histone deacetylase (HDAC), and tyrosinase along with the catecholamine L-DOPA, by using olive biophenols. Here we report the strongest inhibition of BACE-1 from rutin (IC50 : 3.8 nM) followed by verbascoside (IC50 : 6.3 nM) and olive fruit extract (IC50 : 18 ng), respectively...
May 14, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29767267/hdac-inhibitors-trichostatin-a-and-valproic-acid-increase-e%C3%A2-cadherin-and-vimentin-expression-but-inhibit-migration-and-invasion-of-cholangiocarcinoma-cells
#5
Joon Ho Wang, Eun Jeoung Lee, Meiying Ji, Seon Mee Park
The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various cancers. E‑cadherin is a cell‑to‑cell adhesion protein, whereas accumulation of vimentin is related to the development of the spindle shape of the mesenchymal cell phenotype. We investigated the EMT phenotypes of human cholangiocellular carcinoma HuCC‑T1, JCK and SNU‑1079 cell lines. To this end, we measured the expression of E‑cadherin or zonula occludens (ZO)‑1 and vimentin, epithelial and mesenchymal cell markers, respectively, using real‑time reverse transcription‑polymerase chain reaction, western blotting, and immunofluorescence microscopy following treatment with trichostatin A (TSA, 200 nM) or valproic acid (VPA, 0...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29756644/metabolic-and-gene-expression-hallmarks-of-seed-germination-uncovered-by-sodium-butyrate-in-medicago-truncatula
#6
Andrea Pagano, Susana de Sousa Araújo, Anca Macovei, Daniele Dondi, Simone Lazzaroni, Alma Balestrazzi
Since high-quality seeds are essential for successful crop production in challenging environments, understanding the molecular bases of seed vigor will lead to advances in seed technology. Histone deacetylase (HDAC) inhibitors, promoting histone hyperacetylation, are used as tools to explore aspects still uncovered of the abiotic stress response in plants. The aim of this work was to investigate novel signatures of seed germination in Medicago truncatula, using the HDAC inhibitor sodium butyrate (NaB) as stress agent...
May 14, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29706035/silencing-histone-deacetylase-7-alleviates-transforming-growth-factor-%C3%AE-1-induced-profibrotic-responses-in-fibroblasts-derived-from-peyronie-s-plaque
#7
Dong Hyuk Kang, Guo Nan Yin, Min Ji Choi, Kang Moon Song, Kalyan Ghatak, Nguyen Nhat Minh, Mi Hye Kwon, Do Hwan Seong, Ji Kan Ryu, Jun Kyu Suh
PURPOSE: Epigenetic modifications, such as histone acetylation/deacetylation and DNA methylation, play a crucial role in the pathogenesis of inflammatory disorders and fibrotic diseases. The aim of this study was to study the differential gene expression of histone deacetylases (HDACs) in fibroblasts isolated from plaque tissue of Peyronie's disease (PD) or normal tunica albuginea (TA) and to examine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of HDAC7 in fibroblasts derived from human PD plaque...
May 2018: World Journal of Men's Health
https://www.readbyqxmd.com/read/29680681/hdac-inhibition-helps-post-mi-healing-by-modulating-macrophage-polarization
#8
Denise Kimbrough, Sabina H Wang, Lillianne H Wright, Santhosh K Mani, Harinath Kasiganesan, Amanda C LaRue, Qi Cheng, Satish N Nadig, Carl Atkinson, Donald R Menick
AIMS: Following an acute myocardial infarction (MI) the extracellular matrix (ECM) undergoes remodeling in order to prevent dilation of the infarct area and maintain cardiac output. Excessive and prolonged inflammation following an MI exacerbates adverse ventricular remodeling. Macrophages are an integral part of the inflammatory response that contribute to this remodeling. Treatment with histone deacetylase (HDAC) inhibitors preserves LV function and myocardial remodeling in the post-MI heart...
April 19, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29679567/hdac-mediated-deacetylation-of-klf5-associates-with-its-proteasomal-degradation
#9
Ran Tao, Baotong Zhang, Yixiang Li, Jamie L King, Ruoyu Tian, Siyuan Xia, Cara Rae Schiavon, Jin-Tang Dong
Krüppel-like factor 5 (KLF5) is a basic transcription factor that regulates diverse cellular processes during tumor development. Acetylation of KLF5 at lysine 369 (K369) reverses its function from promoting to suppressing cell proliferation and tumor growth. In this study, we examined the regulation of KLF5 by histone deacetylases in the prostate cancer cell line DU 145. While confirming the functions of HDAC1/2 in KLF5 deacetylation and the promotion of cell proliferation, we found that the knockdown of HDAC1/2 upregulated KLF5 protein but not KLF5 mRNA, and the increase in KLF5 protein level by silencing HDAC1/2 was at least in part due to decreased proteasomal degradation...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29670692/discovery-of-novel-indoleamine-2-3-dioxygenase-1-ido1-and-histone-deacetylase-hdac-dual-inhibitors
#10
Kun Fang, Guoqiang Dong, Yu Li, Shipeng He, Ying Wu, Shanchao Wu, Wei Wang, Chunquan Sheng
In order to take advantage of both immunotherapeutic and epigenetic antitumor agents, the first generation of dual indoleamine 2,3-dioxygenase 1 (IDO1) and histone deacetylase (HDAC) inhibitors were designed. The highly active dual inhibitor 10 showed excellent and balanced activity against both IDO1 (IC50 = 69.0 nM) and HDAC1 (IC50 = 66.5 nM), whose dual targeting mechanisms were validated in cancer cells. Compound 10 had good pharmacokinetic profiles as an orally active antitumor agent and significantly reduced the l-kynurenine level in plasma...
April 12, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29667768/quinazoline-based-hydroxamic-acids-design-synthesis-and-evaluation-of-histone-deacetylase-inhibitory-effects-and-cytotoxicity
#11
Doan Thanh Hieu, Duong Tien Anh, Hai Pham-The, Le-Thi-Thu Huong, Eun Jae Park, Jeong Eun Choi, Jong Soon Kang, Sang-Bae Han, Phan Thi Phuong Dung, Nguyen-Hai Nam
In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a-i, 6a-i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g. 4g, 4c, 4g-i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat)...
April 18, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29624006/intrinsic-and-extrinsic-molecular-determinants-or-modulators-for-epigenetic-remodeling-and-reprogramming-of-somatic-cell-derived-genome-in-mammalian-nuclear-transferred-oocytes-and-resultant-embryos
#12
M Samiec, M Skrzyszowska
The efficiency of somatic cell cloning in mammals remains disappointingly low. Incomplete and aberrant reprogramming of epigenetic memory of somatic cell nuclei in preimplantation nuclear- transferred (NT) embryos is one of the most important factors that limit the cloning effectiveness. The extent of epigenetic genome-wide alterations, involving histone or DNA methylation and histone deacetylation, that are mediated by histone-lysine methyltransferases (HMTs) or DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) can be modulated/reversed via exogenous inhibitors of these enzymes throughout in vitro culture of nuclear donor cells, nuclear recipient oocytes and/or cloned embryos...
March 2018: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/29622848/the-hdac-inhibitor-saha-prevents-colonic-inflammation-by-suppressing-pro-inflammatory-cytokines-and-chemokines-in-dss-induced-colitis
#13
Mohmand Noor Ali, Narantsog Choijookhuu, Hideaki Takagi, Naparee Srisowanna, Mai Nguyen Nhat Huynh, Yuya Yamaguchi, Phyu Synn Oo, Myat Tin Htwe Kyaw, Katsuaki Sato, Ryoji Yamaguchi, Yoshitaka Hishikawa
Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract that is caused by multiple factors, including dysfunction of the immune system and genetic and epigenetic alterations. Aberrant epigenetic regulation, especially histone acetylation, was found in biopsies from IBD patients and mouse models of colitis, suggesting that an epigenetic treatment approach may be useful for IBD therapy. Therefore, we investigated the effects of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), in a mouse model of dextran sulfate sodium (DSS)-induced colitis...
February 27, 2018: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/29590644/acetylation-of-gata4-on-lysine-residue-k313-promotes-osteoblastic-cells-growth
#14
Wenjun You, Lijuan Song, Kun Wang
BACKGROUND/AIMS: GATA4, a protein related to osteoblast differentiation and mineralization, whose acetylation is essential for cardiac defects. Here, we aimed to explore the functional impacts of GATA4 acetylation on osteoporosis (OS). METHODS: GATA4 acetylation in hFOB1.19 and 293T cells was detected after exposure of HDAC inhibitors (TSA and SAHA). Co-immunoprecipitation was conducted to determine which HATs and HDACs was involved in the modulation of GATA4 acetylation/deacetylation, and to identify the acetylation site...
March 22, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29588251/effects-of-class-ii-selective-histone-deacetylase-inhibitor-on-neuromuscular-function-and-disease-progression-in-sod1-als-mice
#15
Daniela Buonvicino, Roberta Felici, Giuseppe Ranieri, Riccardo Caramelli, Andrea Lapucci, Leonardo Cavone, Mirko Muzzi, Lorena Di Pietro, Camilla Bernardini, Clemens Zwergel, Sergio Valente, Antonello Mai, Alberto Chiarugi
Emerging evidence indicates that transcriptome alterations due to epigenetic deregulation concur to ALS pathogenesis. Accordingly, pan-histone deacetylase (HDAC) inhibitors delays ALS development in mice, but these compounds failed when tested in ALS patients. Possibly, lack of selectivity towards specific classes of HDACs weakens the therapeutic effects of pan-HDAC inhibitors. Here, we tested the effects of the HDAC Class II selective inhibitor MC1568 on disease evolution, motor neuron survival as well as skeletal muscle function in SOD1G93A mice...
March 24, 2018: Neuroscience
https://www.readbyqxmd.com/read/29587244/epigenetic-regulation-of-vascular-nadph-oxidase-expression-and-reactive-oxygen-species-production-by-histone-deacetylase-dependent-mechanisms-in-experimental-diabetes
#16
Simona-Adriana Manea, Mihaela-Loredana Antonescu, Ioana Madalina Fenyo, Monica Raicu, Maya Simionescu, Adrian Manea
Reactive oxygen species (ROS) generated by up-regulated NADPH oxidase (Nox) contribute to structural-functional alterations of the vascular wall in diabetes. Epigenetic mechanisms, such as histone acetylation, emerged as important regulators of gene expression in cardiovascular disorders. Since their role in diabetes is still elusive we hypothesized that histone deacetylase (HDAC)-dependent mechanisms could mediate vascular Nox overexpression in diabetic conditions. Non-diabetic and streptozotocin-induced diabetic C57BL/6J mice were randomized to receive vehicle or suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor...
March 17, 2018: Redox Biology
https://www.readbyqxmd.com/read/29559532/innate-responses-to-gene-knockouts-impact-overlapping-gene-networks-and-vary-with-respect-to-resistance-to-viral-infection
#17
Yonghong Liu, Yuanyuan Liu, Jiaming Wu, Bernard Roizman, Grace Guoying Zhou
Analyses of the levels of mRNAs encoding IFIT1, IFI16, RIG-1, MDA5, CXCL10, LGP2, PUM1, LSD1, STING, and IFNβ in cell lines from which the gene encoding LGP2, LSD1, PML, HDAC4, IFI16, PUM1, STING, MDA5, IRF3, or HDAC 1 had been knocked out, as well as the ability of these cell lines to support the replication of HSV-1, revealed the following: ( i ) Cell lines lacking the gene encoding LGP2, PML, or HDAC4 (cluster 1) exhibited increased levels of expression of partially overlapping gene networks. Concurrently, these cell lines produced from 5 fold to 12 fold lower yields of HSV-1 than the parental cells...
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29549837/design-synthesis-biological-evaluation-and-in-vivo-testing-of-dual-phosphodiesterase-5-pde5-and-histone-deacetylase-6-hdac6-selective-inhibitors-for-the-treatment-of-alzheimer-s-disease
#18
Obdulia Rabal, Juan A Sánchez-Arias, Mar Cuadrado-Tejedor, Irene de Miguel, Marta Pérez-González, Carolina García-Barroso, Ana Ugarte, Ander Estella-Hermoso de Mendoza, Elena Sáez, Maria Espelosin, Susana Ursua, Tan Haizhong, Wu Wei, Xu Musheng, Ana Garcia-Osta, Julen Oyarzabal
We have identified chemical probes that act as dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors (>1 log unit difference versus class I HDACs) to decipher the contribution of HDAC isoforms to the positive impact of dual-acting PDE5 and HDAC inhibitors on mouse models of Alzheimer's disease (AD) and fine-tune this systems therapeutics approach. Structure- and knowledge-based approaches led to the design of first-in-class molecules with the desired target compound profile: dual PDE5 and HDAC6-selective inhibitors...
April 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29541372/elimination-of-hiv-1-latently-infected-cells-by-gnidimacrin-and-a-selective-hdac-inhibitor
#19
Li Huang, Wei-Hong Lai, Lei Zhu, Wei Li, Lei Wei, Kuo-Hsiung Lee, Lan Xie, Chin-Ho Chen
We have previously reported gnidimacrin (GM), a protein kinase C (PKC) agonist, significantly reduces the frequency of HIV-1 latently infected cells in peripheral blood mononuclear cells (PBMCs) from patients undergoing successful antiretroviral therapy at low picomolar concentrations ex vivo , which is distinct from other latency reversing agents. In this study, we demonstrate that strong viral reactivation by GM is a mechanism for elimination of latently infected cells, and a histone deacetylase inhibitor (HDACI), a thiophenyl benzamide (TPB), further potentiated the efficacy of GM against latent HIV-1...
March 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29534238/targeting-epigenetic-dna-and-histone-modifications-to-treat-kidney-disease
#20
Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
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