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https://www.readbyqxmd.com/read/29782940/defining-osteoblast-and-adipocyte-lineages-in-the-bone-marrow
#1
J L Pierce, D L Begun, J J Westendorf, M E McGee-Lawrence
Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood...
May 18, 2018: Bone
https://www.readbyqxmd.com/read/29782174/expression-of-concentrative-nucleoside-transporters-slc28a-in-the-human-placenta-effects-of-gestation-age-and-prototype-differentiation-affecting-agents
#2
Lucie Jiraskova, Lukas Cerveny, Sara Karbanova, Zuzana Ptackova, Frantisek Staud
Equilibrative ( SLC29A) and concentrative ( SLC28A) nucleoside transporters contribute to proper placental development and mediate uptake of nucleosides/nucleoside-derived drugs. We analyzed placental expression of SLC28A mRNA during gestation. Moreover, we studied in choriocarcinoma-derived BeWo cells whether SLC29A and SLC28A mRNA levels can be modulated by activity of adenylyl cyclase, retinoic acid receptor activation, CpG islands methylation, or histone acetylation, using forskolin, all- trans-retinoic acid, and 5-azacytidine, and sodium butyrate/sodium valproate, respectively...
May 21, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29776834/bet-bromodomain-ligands-probing-the-wpf-shelf-to-improve-brd4-bromodomain-affinity-and-metabolic-stability
#3
Laura E Jennings, Matthias Schiedel, David S Hewings, Sarah Picaud, Corentine M C Laurin, Paul A Bruno, Joseph P Bluck, Amy R Scorah, Larissa See, Jessica K Reynolds, Mustafa Moroglu, Ishna N Mistry, Amy Hicks, Pavel Guzanov, James Clayton, Charles N G Evans, Giulia Stazi, Philip C Biggin, Anna K Mapp, Ester M Hammond, Philip G Humphreys, Panagis Filippakopoulos, Stuart J Conway
Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t½  = 39.8 min). Structure-guided optimisation of compound properties led to the development of the 3-pyridyl-derived OXFBD04...
May 15, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29775417/targeting-histone-methyltransferase-enhancer-of-zeste-homolog-2-inhibits-renal-epithelial-mesenchymal-transition-and-attenuates-renal-fibrosis
#4
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29774080/microrna-193b-3p-regulates-chondrogenesis-and-chondrocyte-metabolism-by-targeting-hdac3
#5
Fangang Meng, Zhiwen Li, Zhiqi Zhang, Zibo Yang, Yan Kang, Xiaoyi Zhao, Dianbo Long, Shu Hu, Minghui Gu, Suiwen He, Peihui Wu, Zongkun Chang, Aishan He, Weiming Liao
Histone deacetylase 3 (HDAC3) plays a pivotal role in the repression of cartilage-specific gene expression in human chondrocytes. The aim of this study was to determine whether microRNA-193b-3p (miR-193b-3p) regulates the expression of HDAC3 during chondrogenesis and chondrocyte metabolism. Methods: miR-193b-3p expression was assessed in a human mesenchymal stem cell (hMSC) model of chondrogenesis, in interleukin-1β (IL-1β)-treated primary human chondrocytes (PHCs), and in non-degraded and degraded cartilage...
2018: Theranostics
https://www.readbyqxmd.com/read/29774040/-oligocellula1-high-expression-of-osmotically-responsive-genes15-promotes-cell-proliferation-with-histone-deacetylase9-and-powerdress-during-leaf-development-in-arabidopsis-thaliana
#6
Marina Suzuki, Nanae Shinozuka, Tomohiro Hirakata, Miyuki T Nakata, Taku Demura, Hirokazu Tsukaya, Gorou Horiguchi
Organ size regulation is dependent on the precise spatial and temporal regulation of cell proliferation and cell expansion. A number of transcription factors have been identified that play a key role in the determination of aerial lateral organ size, but their functional relationship to various chromatin modifiers has not been well understood. To understand how leaf size is regulated, we previously isolated the oligocellula1 ( oli1 ) mutant of Arabidopsis thaliana that develops smaller first leaves than the wild type (WT) mainly due to a reduction in the cell number...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29773854/genome-wide-haplotype-association-analysis-of-primary-biliary-cholangitis-risk-in-japanese
#7
Cindy Im, Yadav Sapkota, Wonjong Moon, Minae Kawashima, Minoru Nakamura, Katsushi Tokunaga, Yutaka Yasui
Primary biliary cholangitis (PBC) susceptibility loci have largely been discovered through single SNP association testing. In this study, we report genic haplotype patterns associated with PBC risk genome-wide in two Japanese cohorts. Among the 74 genic PBC risk haplotype candidates we detected with a novel methodological approach in a discovery cohort of 1,937 Japanese, nearly two-thirds were replicated (49 haplotypes, Bonferroni-corrected P < 6.8 × 10-4 ) in an independent Japanese cohort (N = 949)...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772349/divergent-evolutionary-origins-and-biogeographic-histories-of-two-freshwater-crabs-brachyura-potamonautes-on-the-west-african-conveyer-belt-islands-of-s%C3%A3-o-tom%C3%A3-and-pr%C3%A3-ncipe
#8
Savel R Daniels, Sebastian Klaus
We examined the colonization history and phylogeographic structure of the two endemic freshwater crab species (Potamonautes margaritarius and P. principe) inhabiting the volcanic islands of São Tomé and Príncipe, respectively, using mitochondrial and nuclear DNA sequence data. All samples were sequenced for the mtDNA COI locus and used in the phylogeographic analyses, while a single specimen per lineage was sequenced for the two remaining loci (16S rRNA and histone 3) and used in the phylogenetic reconstruction...
May 14, 2018: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/29772299/biophenols-enzymes-%C3%AE-secretase-cholinesterases-histone-deacetylase-and-tyrosinase-inhibitors-from-olive-olea-europaea-l
#9
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/29769286/targeted-inhibition-of-histone-h3k27-demethylation-is-effective-in-high-risk-neuroblastoma
#10
Timothy L Lochmann, Krista M Powell, Jungoh Ham, Konstantinos V Floros, Daniel A R Heisey, Richard I J Kurupi, Marissa L Calbert, Maninderjit S Ghotra, Patricia Greninger, Mikhail Dozmorov, Madhu Gowda, Andrew J Souers, C Patrick Reynolds, Cyril H Benes, Anthony C Faber
High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death...
May 16, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29769011/evolving-strategies-for-the-treatment-of-t-cell-lymphoma-a-systematic-review-and-recent-patents
#11
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
OBJECTIVE: Mature T-cell lymphomas are a heterogeneous group of T-cell malignancies with a poor outcome. The discovery of new molecular biomarkers has led to the emergence of new drugs in recent years that target various signaling pathways. METHOD: We examined all pertinent published patents through 2015 that analyzed novel methods for the diagnosis and treatment of T cell lymphoma, as well as related published and unpublished studies. Selection criteria were established before data collection...
May 16, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29766333/treatment-of-donor-cells-with-recombinant-kdm4d-protein-improves-preimplantation-development-of-cloned-ovine-embryos
#12
Yumei Zhang, Qianqian Wang, Kailing Liu, Enen Gao, Hong Guan, Jian Hou
Incomplete epigenetic reprogramming is one of the major factors affecting the development of embryos cloned by somatic cell nuclear transfer (SCNT). Histone 3 lysine 9 (H3K9) trimethylation has been identified as a key barrier to efficient reprogramming by SCNT. The aim of this study was to explore a method of downregulating H3K9me3 levels in donor cells by using histone lysine demethylase (KDM) protein. When sheep fetal fibroblast cells were treated with recombinant human KDM4D protein (rhKDM4D), the levels of H3K9 trimethylation and dimethylation were both significantly decreased...
May 15, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29765262/a-new-notomastus-annelida-capitellidae-species-from-korean-waters-with-genetic-comparison-based-on-three-gene-markers
#13
Man-Ki Jeong, Ho Young Soh, Jin Hee Wi, Hae-Lip Suh
Notomastus koreanus sp. n. , collected from the sublittoral muddy bottom of Korean waters, is described as a new species. The Korean new species closely resembles N. torquatus Hutchings & Rainer, 1979 in the chaetal arrangement and the details of abdominal segments, but differs in the position of genital pores and the absence of eyes. DNA sequences (mtCOI, 16S rRNA, and histone H3) of the new species were compared with all the available sequences of Notomastus species in the GenBank database. Three genes showed significant genetic differences between the new species and its congeners (COI: 51...
2018: ZooKeys
https://www.readbyqxmd.com/read/29764959/a-targeted-rnai-screen-reveals-drosophila-female-sterile-genes-that-control-the-size-of-germline-stem-cell-niche-during-development
#14
Yueh Cho, Chun-Ming Lai, Kun-Yang Lin, Hwei-Jan Hsu
Adult stem cells maintain tissue homeostasis. This unique capability largely depends on the stem cell niche, a specialized microenvironment, which preserves stem cell identity through physical contacts and secreted factors. In many cancers, latent tumor cell niches are thought to house stem cells and aid tumor initiation. However, in developing tissue and cancer it is unclear how the niche is established. The well-characterized germline stem cells (GSCs) and niches in the Drosophila melanogaster ovary provide an excellent model to address this fundamental issue...
May 15, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29764755/investigations-on-small-molecule-inhibitors-targeting-the-histone-h3k4-tri-methyllysine-binding-phd-finger-of-jmjc-histone-demethylases
#15
REVIEW
Bhaskar Bhushan, Alexandre Erdmann, Yijia Zhang, Roman Belle, Catrine Johannson, Udo Oppermann, Richard J Hopkinson, Christopher J Schofield, Akane Kawamura
Plant homeodomain (PHD) containing proteins are important epigenetic regulators and are of interest as potential drug targets. Inspired by the amiodarone derivatives reported to inhibit the PHD finger 3 of KDM5A (KDM5A(PHD3)), a set of compounds were synthesised. Amiodarone and its derivatives were observed to weakly disrupt the interactions of a histone H3K4me3 peptide with KDM5A(PHD3). Selected amiodarone derivatives inhibited catalysis of KDM5A, but in a PHD-finger independent manner. Amiodarone derivatives also bind to H3K4me3-binding PHD-fingers from the KDM7 subfamily...
March 19, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29763912/-a-succinate-ether-derivative-of-tocotrienol-enhances-dickkopf-1-gene-expression-through-epigenetic-alterations-in-malignant-mesothelioma-cells
#16
Ayami Sato, Haruka Ueno, Momoka Fusegi, Saki Kaneko, Kakeru Kohno, Nantiga Virgona, Akira Ando, Yuko Sekine, Tomohiro Yano
BACKGROUND: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1)...
May 15, 2018: Pharmacology
https://www.readbyqxmd.com/read/29763664/dna-profiling-reveals-neobenedenia-girellae-as-the-primary-culprit-in-global-fisheries-and-aquaculture
#17
Alexander K Brazenor, Terry Bertozzi, Terrence L Miller, Ian D Whittington, Kate S Hutson
Accurate identification of parasite species and strains is crucial to mitigate the risk of epidemics and emerging disease. Species of Neobenedenia are harmful monogenean ectoparasites that infect economically important bony fishes in aquaculture worldwide, however, the species boundaries between two of the most notorious taxa, N. melleni and N. girellae, has been a topic of contention for decades. Historically, identifications of Neobenedenia isolates have overwhelmingly been attributed to N. melleni, and it has been proposed that N...
May 12, 2018: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/29763623/molecular-pathological-radiological-and-immune-profiling-of-non-brainstem-pediatric-high-grade-glioma-from-the-herby-phase-ii-randomized-trial
#18
Alan Mackay, Anna Burford, Valeria Molinari, David T W Jones, Elisa Izquierdo, Jurriaan Brouwer-Visser, Felice Giangaspero, Christine Haberler, Torsten Pietsch, Thomas S Jacques, Dominique Figarella-Branger, Daniel Rodriguez, Paul S Morgan, Pichai Raman, Angela J Waanders, Adam C Resnick, Maura Massimino, Maria Luisa Garrè, Helen Smith, David Capper, Stefan M Pfister, Thomas Würdinger, Rachel Tam, Josep Garcia, Meghna Das Thakur, Gilles Vassal, Jacques Grill, Tim Jaspan, Pascale Varlet, Chris Jones
The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8+ tumor-infiltrating lymphocytes, and longer survival with the addition of BEV...
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29762469/individualised-multimodal-treatment-strategies-for-anaplastic-and-poorly-differentiated-thyroid-cancer
#19
Sabine Wächter, Annette Wunderlich, Silvia Roth, Ioannis Mintziras, Elisabeth Maurer, Sebastian Hoffmann, Frederik A Verburg, Sebastian A Fellinger, Katharina Holzer, Detlef K Bartsch, Pietro Di Fazio
The prognosis of anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC) is poor, due to their radioiodine refractoriness (RAI-R), high metastatic potential and current lack of effective treatment strategies. We aimed to examine the efficacy of the tyrosine kinase inhibitors (TKIs) sorafenib and selumetinib and the histone deacetylase inhibitor (HDACI) panobinostat in patient-derived tumor tissue (PDTT) of ATCs/PDTCs, the expression of sodium iodide symporter ( NIS ) and radioiodine up-take (RAI-U)...
May 15, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29760409/histone-deacetylase-inhibitor-ms-275-restores-social-and-synaptic-function-in-a-shank3-deficient-mouse-model-of-autism
#20
Kaijie Ma, Luye Qin, Emmanuel Matas, Lara J Duffney, Aiyi Liu, Zhen Yan
Autism is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Genetic screening has identified synaptic, transcriptional, and chromatin genes disrupted in autistic patients. Haploinsufficiency of Shank3, which encodes a scaffold protein at glutamatergic synapses, is causally linked to autism. Using a Shank3-deficient mouse model that exhibits prominent autism-like phenotypes, we have found that histone acetylation in the prefrontal cortex (PFC) is abnormally low, which can be reversed by MS-275 (also known as Entinostat, SNDX-275), a class I histone deacetylase (HDAC) inhibitor that is selectively potent in PFC...
April 19, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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