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https://www.readbyqxmd.com/read/28502669/biomimetic-tendon-extracellular-matrix-composite-gradient-scaffold-enhances-ligament-to-bone-junction-reconstruction
#1
Huanhuan Liu, Long Yang, Erchen Zhang, Rui Zhang, Dandan Cai, Shouan Zhu, Jisheng Ran, Varitsara Bunpetch, Youzhi Cai, Boon Chin Heng, Yejun Hu, Xuesong Dai, Xiao Chen, Hongwei Ouyang
Management of ligament/tendon-to-bone-junction healing remains a formidable challenge in the field of orthopedic medicine to date, due to deficient vascularity and multi-tissue transitional structure of the junction. Numerous strategies have been employed to improve ligament-bone junction healing, including delivery of stem cells, bioactive factors, and synthetic materials, but these methods are often inadequate at recapitulating the complex structure-function relationships at native tissue interfaces. Here, we developed an easily-fabricated and effective biomimetic composite to promote the regeneration of ligament-bone junction by physically modifying the tendon extracellular matrix (ECM) into a Random-Aligned-Random composite using ultrasound treatment...
May 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28487543/kdm6b-modulates-mapk-pathway-mediating-multiple-myeloma-cell-growth-and-survival
#2
H Ohguchi, T Harada, M Sagawa, S Kikuchi, Y-T Tai, P G Richardson, T Hideshima, K C Anderson
Recent studies have delineated cancer type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM); and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. TNFα or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKβ inhibitor MLN120B, suggesting KDM6B is regulated by NF-κB signaling in MM cells. RNA-sequencing and subsequent ChIP-qPCR analyses reveal that KDM6B is recruited to the loci of genes encoding components of MAPK signaling pathway including ELK1 and FOS, and upregulates these genes expression without affecting H3K27 methylation level...
May 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28469799/histone-h3k14-hypoacetylation-and-h3k27-hypermethylation-along-with-hdac1-up-regulation-and-kdm6b-down-regulation-are-associated-with-active-pulmonary-tuberculosis-disease
#3
Yung-Che Chen, Tung-Ying Chao, Sum-Yee Leung, Chung-Jen Chen, Chao-Chien Wu, Wen-Feng Fang, Yi-Hsi Wang, Huang-Chih Chang, Ting-Ya Wang, Yong-Yong Lin, Yi-Xin Zheng, Meng-Chih Lin, Chang-Chun Hsiao
The aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in active pulmonary tuberculosis (TB) disease. Global histone H3K27me3, H3K27me2, H3K9me3, H3K9Ac, and H3K14Ac expressions, and their modifying enzyme expressions, including KDM1A, KDM6B, EZH2, HDAC1, and HDAC2, were assessed in blood leukocytes from 81 patients with active pulmonary TB disease and 44 matched healthy subjects (HS). TLR2, TNF-α, IFN-γ, and IL12B-specific histone enrichment of peripheral blood mononuclear cells was measured by chromatin immunoprecipitation method...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28455435/cd40l-dependent-pathway-is-active-at-various-stages-of-rheumatoid-arthritis-disease-progression
#4
Yanxia Guo, Alice M Walsh, Ursula Fearon, Malcolm D Smith, Mihir D Wechalekar, Xuefeng Yin, Suzanne Cole, Carl Orr, Trudy McGarry, Mary Canavan, Stephan Kelly, Tai-An Lin, Xuejun Liu, Susanna M Proudman, Douglas J Veale, Costantino Pitzalis, Sunil Nagpal
The inflammatory CD40-CD40L pathway is implicated in various autoimmune diseases, but the activity status of this pathway in various stages of rheumatoid arthritis (RA) progression is unknown. In this study, we used gene signatures of CD40L stimulation derived from human immature dendritic cells and naive B cells to assess the expression of CD40-downstream genes in synovial tissues from anti-citrullinated protein Ab-positive arthralgia, undifferentiated arthritis (UA), early RA, and established RA cohorts in comparison with healthy donors...
April 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28413430/next-generation-sequencing-of-non-small-cell-lung-cancer-using-a-customized-targeted-sequencing-panel-emphasis-on-small-biopsy-and-cytology
#5
David M DiBardino, David W Rawson, Anjali Saqi, Jonas J Heymann, Carlos A Pagan, William A Bulman
BACKGROUND: Next-generation sequencing (NGS) with a multi-gene panel is now available for patients with lung adenocarcinoma, but the performance characteristics and clinical utility of this testing are not well-described. We present the results of an extended 467 gene panel in a series of advanced, highly selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens, including predominantly small biopsy and cytology specimens. MATERIALS AND METHODS: A retrospective review of 22 NSCLC biopsies sent for NGS using an extended gene panel from January 2014 to July 2015...
2017: CytoJournal
https://www.readbyqxmd.com/read/28384648/regulation-of-the-jmjd3-kdm6b-histone-demethylase-in-glioblastoma-stem-cells-by-stat3
#6
Maureen M Sherry-Lynes, Sejuti Sengupta, Shreya Kulkarni, Brent H Cochran
The growth factor and cytokine regulated transcription factor STAT3 is required for the self-renewal of several stem cell types including tumor stem cells from glioblastoma. Here we show that STAT3 inhibition leads to the upregulation of the histone H3K27me2/3 demethylase Jmjd3 (KDM6B), which can reverse polycomb complex-mediated repression of tissue specific genes. STAT3 binds to the Jmjd3 promoter, suggesting that Jmjd3 is a direct target of STAT3. Overexpression of Jmjd3 slows glioblastoma stem cell growth and neurosphere formation, whereas knockdown of Jmjd3 rescues the STAT3 inhibitor-induced neurosphere formation defect...
2017: PloS One
https://www.readbyqxmd.com/read/28372944/histone-demethylases-kdm6ba-and-kdm6bb-redundantly-promote-cardiomyocyte-proliferation-during-zebrafish-heart-ventricle-maturation
#7
Alexander A Akerberg, Astra Henner, Scott Stewart, Kryn Stankunas
Trimethylation of lysine 27 on histone 3 (H3K27me3) by the Polycomb repressive complex 2 (PRC2) contributes to localized and inherited transcriptional repression. Kdm6b (Jmjd3) is a H3K27me3 demethylase that can relieve repression-associated H3K27me3 marks, thereby supporting activation of previously silenced genes. Kdm6b is proposed to contribute to early developmental cell fate specification, cardiovascular differentiation, and/or later steps of organogenesis, including endochondral bone formation and lung development...
April 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28322580/macrophage-kdm6b-controls-the-pro-fibrotic-transcriptome-signature-of-foam-cells
#8
Annette E Neele, Koen Hm Prange, Marten A Hoeksema, Saskia van der Velden, Tina Lucas, Stefanie Dimmeler, Esther Lutgens, Jan Van den Bossche, Menno Pj de Winther
AIM: In order to identify regulators of foam cells, we studied the H3K27 demethylase Kdm6b (also known as Jmjd3), a known regulator of macrophages, in controlling the transcriptional profile of foam cells. MATERIALS & METHODS: Foam cells from Kdm6b-deleted or Kdm6b wild-type mice were isolated and used for RNA-sequencing analysis. RESULTS: Pathway analysis revealed that pro-fibrotic pathways were strongly suppressed in Kdm6b-deleted foam cells...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28314754/kdm6b-regulates-cartilage-development-and-homeostasis-through-anabolic-metabolism
#9
Jun Dai, Dongsheng Yu, Yafei Wang, Yishan Chen, Heng Sun, Xiaolei Zhang, Shouan Zhu, Zongyou Pan, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang
OBJECTIVES: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms. METHODS: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic Col2a1-CreER(T2);Kdm6b(f/f) ...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28228757/regulation-of-epigenetic-modifiers-including-kdm6b-by-interferon-%C3%AE-and-interleukin-4-in-human-macrophages
#10
Gökçe Yıldırım-Buharalıoğlu, Mark Bond, Graciela B Sala-Newby, Charles C T Hindmarch, Andrew C Newby
BACKGROUND: Interferon-γ (IFN-γ) or interleukin-4 (IL-4) drives widely different transcriptional programs in macrophages. However, how IFN-γ and IL-4 alter expression of histone-modifying enzymes involved in epigenetic regulation and how this affects the resulting phenotypic polarization is incompletely understood. METHODS AND RESULTS: We investigated steady-state messenger RNA levels of 84 histone-modifying enzymes and related regulators in colony-stimulating factor-1 differentiated primary human macrophages using quantitative polymerase chain reaction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209718/demethylation-of-h3k27-is-essential-for-the-induction-of-direct-cardiac-reprogramming-by-mir-combo
#11
Sophie Dal-Pra, Conrad P Hodgkinson, Maria Mirotsou, Imke Kirste, Victor J Dzau
RATIONALE: Direct reprogramming of cardiac fibroblasts to cardiomyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of 4 microRNAs (miR-1, miR-133, miR-208, and miR-499) that we named miR combo. However, the mechanism of miR combo mediated direct cardiac reprogramming is currently unknown. OBJECTIVE: Here, we investigated the possibility that miR combo initiated direct cardiac reprogramming through an epigenetic mechanism...
April 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/28197626/kdm6a-and-kdm6b-altered-expression-in-malignant-pleural-mesothelioma
#12
Sian Cregan, Maeve Breslin, Gerard Roche, Sigrid Wennstedt, Lauren MacDonagh, Cinaria Albadri, Yun Gao, Kenneth J O'Byrne, Sinead Cuffe, Stephen P Finn, Steven G Gray
Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28064082/novel-flavonol-analogues-as-potential-inhibitors-of-jmjd3-histone-demethylase-a-study-based-on-molecular-modelling
#13
Sanchari Basu Mallik, Aravinda Pai, Rekha R Shenoy, B S Jayashree
Epigenetic modulation of gene expression has drawn enormous attention among researchers globally in the present scenario. Since their discovery, Jmj-C histone demethylases were identified as useful markers in understanding the role of epigenetics in inflammatory conditions and in cancer as well. This has created arousal of interest in search of suitable candidates. Potential inhibitors from various other scaffolds such as hydroxyquinolines, hydroxamic acids and triazolopyridines have already been identified and reported...
December 13, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28031467/maternal-sall4-is-indispensable-for-epigenetic-maturation-of-mouse-oocytes
#14
Kai Xu, Xia Chen, Hui Yang, Yiwen Xu, Yuanlin He, Chenfei Wang, Hua Huang, Baodong Liu, Wenqiang Liu, Jingyi Li, Xiaochen Kou, Yanhong Zhao, Kun Zhao, Linfeng Zhang, Zhenzhen Hou, Hong Wang, Hailin Wang, Jing Li, Hengyu Fan, Fengchao Wang, Yawei Gao, Yong Zhang, Jiayu Chen, Shaorong Gao
Sall4 (Splat-like 4) plays important roles in maintaining pluripotency of embryonic stem cells and in various developmental processes. Here, we find that Sall4 is highly expressed in oocytes and early embryos. To investigate the roles of SALL4 in oogenesis, we generated Sall4 maternal specific knock-out mice by using CRISPR/Cas9 system, and we find that the maternal deletion of Sall4 causes developmental arrest of oocytes at germinal vesicle stage with non-surrounded nucleus, and the subsequent meiosis resumption is prohibited...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27800026/hypoxia-increases-genome-wide-bivalent-epigenetic-marking-by-specific-gain-of-h3k27me3
#15
Peggy Prickaerts, Michiel E Adriaens, Twan van den Beucken, Elizabeth Koch, Ludwig Dubois, Vivian E H Dahlmans, Caroline Gits, Chris T A Evelo, Michelle Chan-Seng-Yue, Bradly G Wouters, Jan Willem Voncken
BACKGROUND: Trimethylation at histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) controls gene activity during development and differentiation. Whether H3K4me3 and H3K27me3 changes dynamically in response to altered microenvironmental conditions, including low-oxygen conditions commonly present in solid tumors, is relatively unknown. Demethylation of H3K4me3 and H3K27me3 is mediated by oxygen and 2-oxoglutarate dioxygenases enzymes, suggesting that oxygen deprivation (hypoxia) may influence histone trimethylation...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27755585/microrna-941-expression-in-polymorphonuclear-granulocytes-is-not-related-to-granulomatosis-with-polyangiitis
#16
Jesper Brink Svendsen, Bo Baslund, Elisabeth Præstekjær Cramer, Nicolas Rapin, Niels Borregaard, Jack Bernard Cowland
Jumonji Domain-Containing Protein 3 (JMJD3)/lysine demethylase 6B (KDM6B) is an epigenetic modulator that removes repressive histone marks on genes. Expression of KDM6B mRNA is elevated in leukocytes from patients with ANCA-associated vasculitis (AAV) and has been suggested to be the reason for higher proteinase 3 (PR3) mRNA expression in these cells due to derepression of PRTN3 gene transcription. MicroRNA-941 (miR-941) has been shown to target KDM6B mRNA and inhibit JMJD3 production. We therefore investigated whether polymorphonuclear granulocytes (PMNs) from patients suffering from granulomatosis with polyangiitis (GPA) have lower expression of miR-941 than healthy control donors as a biological cause for higher JMJD3 levels...
2016: PloS One
https://www.readbyqxmd.com/read/27742770/inhibition-of-demethylase-kdm6b-sensitizes-diffuse-large-b-cell-lymphoma-to-chemotherapeutic-drugs
#17
Rohit Mathur, Lalit Sehgal, Ondrej Havranek, Stefan Köhrer, Tamer Khashab, Neeraj Jain, Jan A Burger, Sattva S Neelapu, R Eric Davis, Felipe Samaniego
Histone methylation and demethylation regulate B-cell development, and their deregulation correlates with tumor chemoresistance in diffuse large B-cell lymphoma, limiting cure rates. Since histone methylation status correlates with disease aggressiveness and relapse, we investigated the therapeutic potential of inhibiting histone 3 Lys27 demethylase KDM6B, in vitro, using the small molecule inhibitor GSK-J4. KDM6B is overexpressed in the germinal center B-cell subtype of diffuse large B-cell lymphoma, and higher KDM6B levels are associated with worse survival in patients with diffuse large B-cell lymphoma treated with R-CHOP...
February 2017: Haematologica
https://www.readbyqxmd.com/read/27617932/regional-glutamine-deficiency-in-tumours-promotes-dedifferentiation-through-inhibition-of-histone%C3%A2-demethylation
#18
Min Pan, Michael A Reid, Xazmin H Lowman, Rajan P Kulkarni, Thai Q Tran, Xiaojing Liu, Ying Yang, Jenny E Hernandez-Davies, Kimberly K Rosales, Haiqing Li, Willy Hugo, Chunying Song, Xiangdong Xu, Dustin E Schones, David K Ann, Viviana Gradinaru, Roger S Lo, Jason W Locasale, Mei Kong
Poorly organized tumour vasculature often results in areas of limited nutrient supply and hypoxia. Despite our understanding of solid tumour responses to hypoxia, how nutrient deprivation regionally affects tumour growth and therapeutic response is poorly understood. Here, we show that the core region of solid tumours displayed glutamine deficiency compared with other amino acids. Low glutamine in tumour core regions led to dramatic histone hypermethylation due to decreased α-ketoglutarate levels, a key cofactor for the Jumonji-domain-containing histone demethylases...
October 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27529370/kdm6b-histone-demethylase-is-an-epigenetic-regulator-of-estrogen-receptor-%C3%AE-expression-in-human-pleural-mesothelioma
#19
Arcangela G Manente, Giulia Pinton, Sara Zonca, Daniela Tavian, Tanwir Habib, Puthen V Jithesh, Dean Fennell, Stefan Nilsson, Laura Moro
AIM: To assess the correlation between KDM6B and estrogen receptor β (ERβ) expression in malignant pleural mesothelioma (MPM). MATERIALS & METHODS: We evaluated gene expression by in silico analysis of microarray data, real-time PCR and western blot in MPM tumors and cell lines. RESULTS & CONCLUSION: We report a strong positive correlation between the expression of KDM6B and ERβ in MPM tumors and cell lines. We describe that, in hypoxia, the HIF2α-KDM6B axis induces an epithelioid morphology and ERβ expression in biphasic MPM cells with estrogen receptor-negative phenotype...
September 2016: Epigenomics
https://www.readbyqxmd.com/read/27514027/epigenetic-gene-regulation-by-histone-demethylases-emerging-role-in-oncogenesis-and-inflammation
#20
M K Kang, S Mehrazarin, N-H Park, C-Y Wang
Histone N-terminal tails of nucleosomes are the sites of complex regulation of gene expression through post-translational modifications. Among these modifications, histone methylation had long been associated with permanent gene inactivation until the discovery of Lys-specific demethylase (LSD1), which is responsible for dynamic gene regulation. There are more than 30 members of the Lys demethylase (KDM) family, and with exception of LSD1 and LSD2, all other KDMs possess the Jumonji C (JmjC) domain exhibiting demethylase activity and require unique cofactors, for example, Fe(II) and α-ketoglutarate...
August 11, 2016: Oral Diseases
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