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5-azacytidine

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https://www.readbyqxmd.com/read/29676176/effect-of-mecp2-on-tgf-%C3%AE-1-induced-extracellular-matrix-production-in-nasal-polyp-derived-fibroblasts
#1
Jae-Min Shin, Ji-Young Um, Seoung-Ae Lee, Il-Ho Park, Soo-Hyung Lee, Heung-Man Lee
Purpose Methyl-CpG-binding protein 2 (MeCP2), known as a transcriptional regulator, has been suggested to play an important role in myofibroblast differentiation in the lung. The purpose of this study was to investigate the role of MeCP2 in transforming growth factor (TGF)- β1-induced myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts (NPDFs). Methods To identify the expression of MeCP2 in nasal polyp tissues, immunohistochemistry staining and Western blot were performed...
January 1, 2018: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/29665002/three-dimensional-collagenous-niche-and-azacytidine-selectively-promote-time-dependent-cardiomyogenesis-from-human-bone-marrow-derived-msc-spheroids
#2
Jyotsna Joshi, Gautam Mahajan, Chandrasekhar R Kothapalli
Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure-function-mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time-dependent evolution of cardiomyogenesis from human bone marrow-derived mesenchymal stem cells (BM-MSC)...
April 17, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29649665/the-anti-fecundity-effect-of-5-azacytidine-5-azac-on-schistosoma-mansoni-is-linked-to-dis-regulated-transcription-translation-and-stem-cell-activities
#3
Kathrin K Geyer, Sabrina E Munshi, Martin Vickers, Michael Squance, Toby J Wilkinson, Daniel Berrar, Cristian Chaparro, Martin T Swain, Karl F Hoffmann
Uncontrolled host immunological reactions directed against tissue-trapped eggs precipitate a potentially lethal, pathological cascade responsible for schistosomiasis. Blocking schistosome egg production, therefore, presents a strategy for simultaneously reducing immunopathology as well as limiting disease transmission in endemic or emerging areas. We recently demonstrated that the ribonucleoside analogue 5-azacytidine (5-AzaC) inhibited Schistosoma mansoni oviposition, egg maturation and ovarian development...
April 1, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29623456/use-of-5-azacytidine-in-a-proof-of-concept-study-to-evaluate-the-impact-of-pre-natal-and-post-natal-exposures-as-well-as-within-generation-persistent-dna-methylation-changes-in-daphnia
#4
Camila Gonçalves Athanasio, Ulf Sommer, Mark R Viant, James Kevin Chipman, Leda Mirbahai
Short-term exposures at critical stages of development can lead to delayed adverse effects long after the initial stressor has been removed, a concept referred to as developmental origin of adult disease. This indicates that organisms' phenotypes may epigenetically reflect their past exposure history as well as reflecting chemicals currently present in their environment. This concept has significant implications for environmental monitoring. However, there is as yet little or no implementation of epigenetics in environmental risk assessment...
April 5, 2018: Ecotoxicology
https://www.readbyqxmd.com/read/29563491/rna-cytosine-methylation-and-methyltransferases-mediate-chromatin-organization-and-5-azacytidine-response-and-resistance-in-leukaemia
#5
Jason X Cheng, Li Chen, Yuan Li, Adam Cloe, Ming Yue, Jiangbo Wei, Kenneth A Watanabe, Jamile M Shammo, John Anastasi, Qingxi J Shen, Richard A Larson, Chuan He, Michelle M Le Beau, James W Vardiman
The roles of RNA 5-methylcytosine (RNA:m5 C) and RNA:m5 C methyltransferases (RCMTs) in lineage-associated chromatin organization and drug response/resistance are unclear. Here we demonstrate that the RCMTs, namely NSUN3 and DNMT2, directly bind hnRNPK, a conserved RNA-binding protein. hnRNPK interacts with the lineage-determining transcription factors (TFs), GATA1 and SPI1/PU.1, and with CDK9/P-TEFb to recruit RNA-polymerase-II at nascent RNA, leading to formation of 5-Azacitidine (5-AZA)-sensitive chromatin structure...
March 21, 2018: Nature Communications
https://www.readbyqxmd.com/read/29534238/targeting-epigenetic-dna-and-histone-modifications-to-treat-kidney-disease
#6
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
https://www.readbyqxmd.com/read/29518866/-the-effect-of-dna-hydroxymethylase-tet2-on-%C3%AE-globin-activation-in-the-treatment-of-%C3%AE-thalassemia
#7
W X Li, Q W Ma, F Y Zeng
Objective: To study the function of ten-eleven translocation 2 (Tet2) in γ globin gene expression in patients with β- thalassemia. Methods: Gamma globin expression was induced by 5-azacytidine and Tet2 gene expression was knocked down by short hairpin RNA (shRNA) in a human immortalized myelogenous leukemia K562 cell line. The global 5-hydroxymethylcytosine (5hmC) level was measured by an ELISA kit. 5hmC level of γ globin gene was quantified by sulfite sequencing. The mRNA level of Tet2, γ globin, and related transcription factors Nfe4 and Klf1 were quantified by real-time PCR...
March 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29508071/fibrin-scaffold-could-promote-survival-of-the-human-adipose-derived-stem-cells-during-differentiation-into-cardiomyocyte-like-cells
#8
Zahra Bagheri-Hosseinabadi, Seyed Alireza Mesbah-Namin, Parvin Salehinejad, Fatemeh Seyedi
Human adipose-derived stem cells (hADSCs) are capable of differentiation into many cells including cardiac cells. Different types of scaffolds are used for cell differentiation but the best is yet to be determined. In this study, fibrin scaffold (3D) was fabricated using human plasma fibrinogen and compared with culture plates (2D) for the growth and differentiation of hADSCs into cardiomyocyte-like cells. For this purpose, after obtaining the properties of the isolated hADSCs and fibrin scaffold, four biochemical tests were employed to determine the relative growth rate of hADSCs in 2D and 3D cultures...
March 6, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29484388/increased-cytomegalovirus-replication-by-5-azacytidine-and-viral-induced-cytoplasmic-expression-of-dnmt%C3%A2-1-in-medulloblastoma-and-endothelial-cells
#9
Atosa Estekizadeh, Natalia Landázur, Jiri Bartek, Christian Beltoft Brøchner, Belghis Davoudi, Helle Broholm, Mohsen Karimi, Tomas J Ekström, Afsar Rahbar
Among all brain tumors diagnosed in children, medulloblastomas (MBs) are associated with a poor prognosis. The etiology of MB is not fully understood, yet the impact of epigenetic alterations of oncogenes has previously been established. During the past decade, the human cytomegalovirus (HCMV) has been detected in several types of cancer, including MB. Since DNA methylation occurs in the cell nucleus and this is considered a host defence response, we studied the impact of HCMV infection on DNA methyltransferase (DNMT‑1) in MB (D324) cells, human umbilical vein endothelial cells (HUVECs) as well as in MB tissue sections...
February 26, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29467326/loss-of-epigenetic-regulator-tet2-and-oncogenic-kit-regulate-myeloid-cell-transformation-via-pi3k-pathway
#10
Lakshmi Reddy Palam, Raghuveer Singh Mali, Baskar Ramdas, Sridhar Nonavinkere Srivatsan, Valeria Visconte, Ramon V Tiu, Bart Vanhaesebroeck, Axel Roers, Alexander Gerbaulet, Mingjiang Xu, Sarath Chandra Janga, Clifford M Takemoto, Sophie Paczesny, Reuben Kapur
Mutations in KIT and TET2 are associated with myeloid malignancies. We show that loss of TET2-induced PI3K activation and -increased proliferation is rescued by targeting the p110α/δ subunits of PI3K. RNA-Seq revealed a hyperactive c-Myc signature in Tet2-/- cells, which is normalized by inhibiting PI3K signaling. Loss of TET2 impairs the maturation of myeloid lineage-derived mast cells by dysregulating the expression of Mitf and Cebpa, which is restored by low-dose ascorbic acid and 5-azacytidine. Utilizing a mouse model in which the loss of TET2 precedes the expression of oncogenic Kit, similar to the human disease, results in the development of a non-mast cell lineage neoplasm (AHNMD), which is responsive to PI3K inhibition...
February 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29467020/insulin-like-growth-factor-1-mediated-regulation-of-mir-193a-expression-promotes-the-migration-and-proliferation-of-c-kit-positive-mouse-cardiac-stem-cells
#11
Yuning Sun, Rongfeng Xu, Jia Huang, Yuyu Yao, Xiaodong Pan, Zhongpu Chen, Genshan Ma
BACKGROUND: C-kit-positive cardiac stem cells (CSCs) have been shown to be a promising candidate treatment for myocardial infarction and heart failure. Insulin-like growth factor (IGF)-1 is an anabolic growth hormone that regulates cellular proliferation, differentiation, senescence, and death in various tissues. Although IGF-1 promotes the migration and proliferation of c-kit-positive mouse CSCs, the underlying mechanism remains unclear. METHODS: Cells were isolated from adult mouse hearts, and c-kit-positive CSCs were separated using magnetic beads...
February 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29452350/extra-virgin-olive-oil-contains-a-metabolo-epigenetic-inhibitor-of-cancer-stem-cells
#12
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29435168/low-fat4-expression-is-associated-with-a-poor-prognosis-in-gastric-cancer-patients
#13
Xiaoting Jiang, Zhengchuang Liu, Yingjie Xia, Jungang Luo, Ji Xu, Xujun He, Houquan Tao
In this study, we investigated the role of Fat atypical cadherin 4 (FAT4) in gastric cancer (GC) progression. Immunohistochemical analysis showed lower FAT4 expression in tumor tissues from GC patients than in normal gastric epithelium. Lower FAT4 expression was associated with poor prognosis, tumor size and invasion, and lymph node and distant metastases. Multivariate analysis showed that TNM stage, lymph node and distant metastases, Lauren classification, and FAT4 expression were independent prognostic factors in GC...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29432154/5-azacytidine-prevents-relapse-and-produces-long-term-complete-remissions-in-leukemia-xenografts-treated-with-moxetumomab-pasudotox
#14
Fabian Müller, Tyler Cunningham, Stephanie Stookey, Chin-Hsien Tai, Sandra Burkett, Parthav Jailwala, Maryalice Stetler Stevenson, Margaret C Cam, Alan S Wayne, Ira Pastan
Moxetumomab pasudotox (Moxe) is a chimeric protein composed of an anti-CD22 Fv fused to a portion of Pseudomonas exotoxin A and kills CD22-expressing leukemia cells. It is very active in hairy-cell leukemia, but many children with relapsed/refractory acute lymphoblastic leukemia (ALL) either respond transiently or are initially resistant. Resistance to Moxe in cultured cells is due to low expression of diphthamide genes (DPH), but only two of six ALL blast samples from resistant patients had low DPH expression...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29302025/aprdx1-mutant-allele-causes-a-mmachc-secondary-epimutation-in-cblc-patients
#15
Jean-Louis Guéant, Céline Chéry, Abderrahim Oussalah, Javad Nadaf, David Coelho, Thomas Josse, Justine Flayac, Aurélie Robert, Isabelle Koscinski, Isabelle Gastin, Pierre Filhine-Tresarrieu, Mihaela Pupavac, Alison Brebner, David Watkins, Tomi Pastinen, Alexandre Montpetit, Fadi Hariri, David Tregouët, Benjamin A Raby, Wendy K Chung, Pierre-Emmanuel Morange, D Sean Froese, Matthias R Baumgartner, Jean-François Benoist, Can Ficicioglu, Virginie Marchand, Yuri Motorin, Chrystèle Bonnemains, François Feillet, Jacek Majewski, David S Rosenblatt
To date, epimutations reported in man have been somatic and erased in germlines. Here, we identify a cause of the autosomal recessive cblC class of inborn errors of vitamin B12 metabolism that we name "epi-cblC". The subjects are compound heterozygotes for a genetic mutation and for a promoter epimutation, detected in blood, fibroblasts, and sperm, at the MMACHC locus; 5-azacytidine restores the expression of MMACHC in fibroblasts. MMACHC is flanked by CCDC163P and PRDX1, which are in the opposite orientation...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29299950/interleukin-17-promotes-the-production-of-underglycosylated-iga1-in-dakiki-cells
#16
Jia-Ru Lin, Ji Wen, Hui Zhang, Li Wang, Fang-Fang Gou, Man Yang, Jun-Ming Fan
BACKGROUND: Interleukin 17 (IL-17) plays an important role in the pathogenesis of autoimmune diseases and might be associated with IgA nephropathy (IgAN). This study aimed to investigate the effect of IL-17 on autoimmune pathogenesis in IgA nephropathy. METHODS: DAKIKI cells were cultured and stimulated with IL-17 to perform dose-dependent and time-dependent experiments. Cell proliferation was examined by cell counting and the Cell Counting Kit-8 (CCK-8) assay. The IgA concentration and the degree of galactosylation in the supernatant were tested using ELISA and a helix aspersa (HAA) lectin binding assay, respectively...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29285667/epigenetic-erasing-and-pancreatic-differentiation-of-dermal-fibroblasts-into-insulin-producing-cells-are-boosted-by-the-use-of-low-stiffness-substrate
#17
Georgia Pennarossa, Rosaria Santoro, Elena F M Manzoni, Maurizio Pesce, Fulvio Gandolfi, Tiziana A L Brevini
Several studies have demonstrated the possibility to revert differentiation process, reactivating hypermethylated genes and facilitating cell transition to a different lineage. Beside the epigenetic mechanisms driving cell conversion processes, growing evidences highlight the importance of mechanical forces in supporting cell plasticity and boosting differentiation. Here, we describe epigenetic erasing and conversion of dermal fibroblasts into insulin-producing cells (EpiCC), and demonstrate that the use of a low-stiffness substrate positively influences these processes...
December 28, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29279013/novel-approaches-to-diagnosis-and-treatment-of-juvenile-myelomonocytic-leukemia
#18
Franco Locatelli, Mattia Algeri, Pietro Merli, Luisa Strocchio
Juvenile myelomonocytic leukemia (JMML) is a clonal hematopoietic disorder of infancy/early childhood, resulting from oncogenic mutations in genes involved in the Ras pathway. As JMML often exhibits an aggressive course, the timing of diagnosis and treatment is critical to outcome. Areas covered: This review summarizes current approaches to diagnosis and treatment of JMML, highlighting most recent insights into genetic and epigenetic mechanisms underlying the disease, and providing an overview of novel potential therapeutic strategies...
February 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29249821/aza-ms-a-novel-multiparameter-mass-spectrometry-method-to-determine-the-intracellular-dynamics-of-azacitidine-therapy-in-vivo
#19
A Unnikrishnan, A N Q Vo, R Pickford, M J Raftery, A C Nunez, A Verma, L B Hesson, J E Pimanda
The cytidine analogue, 5-azacytidine (AZA; 5-AZA-cR), is the primary treatment for myelodysplastic syndrome and chronic myelomonocytic leukaemia. However, only ~50% of treated patients will respond to AZA and the drivers of AZA resistance in vivo are poorly understood. To better understand the intracellular dynamics of AZA upon therapy and decipher the molecular basis for AZA resistance, we have developed a novel, multiparameter, quantitative mass spectrometry method (AZA-MS). Using AZA-MS, we have accurately quantified the abundance of the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA and the cytoplasm within the same sample using nanogram quantities of input material...
November 29, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29246089/expression-and-regulation-of-retinoic-acid-receptor-responders-in-the-human-placenta
#20
Hanna Huebner, Andrea Hartner, Wolfgang Rascher, Reiner Strick R, Sven Kehl, Felix Heindl, David L Wachter, Matthias W Beckmann, Fabian B Fahlbusch, Matthias Ruebner
INTRODUCTION: Retinoic acid (RA) signaling through its receptors (RARA, RARB, RARG, and the retinoic X receptor RXRA) is essential for healthy placental and fetal development. An important group of genes regulated by RA are the RA receptor responders (RARRES1, 2, and 3). We set out to analyze their expression and regulation in healthy and pathologically altered placentas of preeclampsia (PE) and intrauterine growth restriction (IUGR) as well as in trophoblast cell lines. METHODS: We performed immunohistochemical staining on placental sections and analyzed gene expression by real-time polymerase chain reaction...
January 1, 2017: Reproductive Sciences
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