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Ying Shao, Qian-Zhao Chen, Yu-Hua Zeng, Yang Li, Wen-Yan Ren, Lin-Yun Zhou, Rong-Xin Liu, Ke Wu, Jun-Qing Yang, Zhong-Liang Deng, Yu Yu, Wen-Juan Sun, Bai-Cheng He
Rosiglitazone (RSG) is a potent drug used in the treatment of insulin resistance; however, it is associated with marked skeletal toxicity. RSG-induced osteoporosis may contribute to the promotion of adipogenic differentiation at the expense of osteogenic differentiation in bone marrow stromal cells. The aim of this study was to investigate whether RSG-induced bone toxicity can be reversed by combined treatment with all-trans retinoic acid (ATRA). We examined different osteogenic markers in mouse embryonic fibroblasts (MEFs) following treatment with RSG, ATRA, or RSG and ATRA in combination...
October 19, 2016: International Journal of Molecular Medicine
Marion Rouzaire, Aurélie Comptour, Corinne Belville, Damien Bouvier, Gaël Clairefond, Flora Ponelle, Vincent Sapin, Denis Gallot, Loïc Blanchon
Thirty percent of preterm births directly result from preterm premature rupture of fetal membranes (PPROM). Clinical management currently proposes using a collagen plug to mechanically stop loss of amniotic fluid. Vitamin A and its active metabolite (retinoic acid) have well-known pro-healing properties and could thus make good candidates as a proposable adjuvant to this mechanical approach. Here we investigate the molecular mechanisms involved in the pro-healing properties of all-trans retinoic acid (atRA) in fetal membranes via an approach using an in vitro primary amniocyte wound model and transcriptomics...
October 18, 2016: International Journal of Biochemistry & Cell Biology
O Lidický, M Šírová, T Etrych
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7...
October 20, 2016: Physiological Research
Katrin Noack, Oliver H Krämer
The differentiation of hematopoietic stem cells into mature blood cells is a highly ordered process and dysregulation of this process can lead to leukemogenesis. Agents that are used to cure acute promyelocytic leukemia (APL) can induce differentiation and/or apoptosis. Here, we describe how effects of all-trans retinoic acid (ATRA) and histone deacetylase inhibitors (HDACi) on APL cell differentiation can be evaluated by immunoblotting and by flow cytometry. We show how the levels of differentiation-associated transcription factors of the CCAAT enhancer binding protein (C/EBP) family can be determined by Western blot and we explain how the cell surface expression of the leukocyte surface antigen CD11b can be measured by flow cytometry...
2017: Methods in Molecular Biology
Alberto García-Mariscal, Karine Peyrollier, Astrid Basse, Esben Pedersen, Ralph Rühl, Jolanda van Hengel, Cord Brakebusch
The ubiquitously expressed small GTPase RhoA is essential for embryonic development and mutated in different cancers. Functionally, it is well described as a regulator of the actin cytoskeleton, but its role in gene regulation is less understood. Using primary mouse keratinocytes with a deletion of the RhoA gene, we have now been exploring how the loss of RhoA affects gene expression. Performing transcription factor reporter assays, we found a significantly decreased activity of a RAR luciferase reporter in RhoA-null keratinocytes...
October 18, 2016: Small GTPases
Yani Zhang, Yingjie Wang, Qisheng Zuo, Xiaoyan Wang, Dong Li, Beibei Tang, Bichun Li
Several inducers have been used to differentiate embryonic stem cells (ESCs) into male germ cells but the induction process has been inefficient. To solve the problem of low efficiency of inducer for ESCs differentiation into male germ cells, all-trans retinoic acid (ATRA), Am80(the retinoic acid receptor agonist), and estradiol (E2) was used to induce ESCs to differentiate into male germ cells in vitro. ESCs were cultured in media containing ATRA, Am80, or E2 respectively which can differentiate ESCs into a germ cell lineage...
2016: PloS One
Zhen-Hua Chen, Wen-Tao Wang, Wei Huang, Ke Fang, Yu-Meng Sun, Shu-Rong Liu, Xue-Qun Luo, Yue-Qin Chen
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are of great importance in different cell contexts. However, only a very small number of lncRNAs have been experimentally validated and functionally annotated during human hematopoiesis. Here, we report an lncRNA, HOTAIRM1, which is associated with myeloid differentiation and has pivotal roles in the degradation of oncoprotein PML-RARA and in myeloid cell differentiation by regulating autophagy pathways. We first revealed that HOTAIRM1 has different variants that are expressed at different levels in cells and that the expression pattern of HOTAIRM1 is closely related to that of the PML-RARA oncoprotein in acute promyelocytic leukemia (APL) patients...
October 14, 2016: Cell Death and Differentiation
Clark D Ridge, Eugene P Mazzola, Martyn P Coles, Simon F R Hinkley
The commonly occurring, high-cytotoxicity macrolide roridin E has been re-isolated from Stachybotrys atra and characterized by 1- and 2-D NMR spectroscopy. Assignment of the spectral data for roridin E revealed differences from the accepted literature, and spectra are reported herein to aid in future identification. For the first time confirmation of structure was provided by a crystallographic solution for roridin E.
October 13, 2016: Magnetic Resonance in Chemistry: MRC
Sougat Misra, Arun Kumar Selvam, Marita Wallenberg, Aditya Ambati, András Matolcsy, Isabelle Magalhaes, Gilbert Lauter, Mikael Björnstedt
Selective targeting of the PML/RARα oncoprotein demonstrates a successful molecular targeted therapy in acute promyelocytic leukemia (APL) with a typical t(15:17) chromosomal translocation. The zinc-thiolate coordination is critical for structural stability of zinc finger proteins, including the PML moiety of PML/RARα. Based on the known interaction of redox-active selenium compounds with thiolate ligands of zinc, we herein have investigated the abrogatory effects of selenite alone or in combination with all-trans retinoic acid on PML/RARα and the possible effects on differentiation in these cells...
October 8, 2016: Oncotarget
Josef Hájek, Miloš Barták, Jana Hazdrová, Marie Forbelská
Extremophilic lichens and their photosynthesizing photobionts from the cold regions of Earth are adapted to perform photosynthesis at subzero temperatures. To evaluate interspecific differences in the critical temperature for primary photochemical processes of photosynthesis, we exposed lichen thalli of Usnea antarctica, Usnea aurantiaco-atra, and Umbilicaria cylindrica to linear cooling from +20 to -50 °C at a constant rate of 2 °C min(-1). Simultaneously, two chlorophyll fluorescence parameters (FV/FM - potential yield of photosynthetic processes in photosystem II, ΦPSII - effective quantum yield of PS II) evaluating a gradual subzero temperature-induced decline in photosynthetic processes were measured by a modulated fluorometer...
October 8, 2016: Cryobiology
Jun Ando, Miwako Asanuma, Kosuke Dodo, Hiroyuki Yamakoshi, Satoshi Kawata, Katsumasa Fujita, Mikiko Sodeoka
Identification of small-molecule-binding sites in protein is important for drug discovery and analysis of protein function. Modified amino-acid residue(s) can be identified by proteolytic cleavage followed by liquid chromatography-mass spectrometry (LC-MS), but this is often hindered by the complexity of the peptide mixtures. We have developed alkyne-tag Raman screening (ATRaS) for identifying binding sites. In ATRaS, small molecules are tagged with alkyne and form covalent bond with proteins. After proteolysis and HPLC, fractions containing the labeled peptides with alkyne tags are detected by means of surface-enhanced Raman scattering (SERS) using silver nanoparticles and sent to MS/MS to identify the binding site...
October 10, 2016: Journal of the American Chemical Society
Junjie Huang, Min Sun, Zitong Wang, Qiaoxia Zhang, Jin Lou, Yun Cai, Weihong Chen, Xin Du
BACKGROUND: 9 treatments for acute promyelocytic leukemia (APL) have been compared in many randomized controlled trials (RCT). The conclusions have been inconsistent and the purpose of this study is to conduct a network meta-analysis. RESULTS: Rankings of event-free survival are ATRA+RIF (81.2%), ATRA+ATO (69.6%), ATO (50.6%). Rankings of complete remission are ATRA+RIF (79.3%), ATRA+ATO (64.8%), RIF (60.3%), ATO (55.9%). Rankings of avoiding differentiation syndromes are CT (84...
October 4, 2016: Oncotarget
Ebrahim Gilasian, Joachim Ziegler, Mehrdad Parchami-Araghi
Minthodes susae Gilasian & Ziegler sp. nov. (Diptera: Tachinidae), from southwestern Iran, is described and illustrated, and compared with M. brevipennis (Brauer & Bergenstamm) from Turkey. A lectotype is recognised for Pseudomintho brevipennis Brauer & Bergenstamm (currently a species of Minthodes) and its designation is attributed to Mesnil. Minthodes pictipennis Brauer & Bergenstamm is newly recorded from Iran and Turkey, and M. latifacies Herting is reported from Iran for the first time. An identification key to the four Minthodes Brauer & Bergenstamm species known to occur in Iran is provided...
October 4, 2016: Zootaxa
Erin Damery, Dominic A Solimando, J Aubrey Waddell
The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr., President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast...
September 2016: Hospital Pharmacy
Richard F Schlenk, Michael Lübbert, Axel Benner, Alexander Lamparter, Jürgen Krauter, Wolfgang Herr, Hans Martin, Helmut R Salih, Andrea Kündgen, Heinz-A Horst, Peter Brossart, Katharina Götze, David Nachbaur, Mohammed Wattad, Claus-Henning Köhne, Walter Fiedler, Martin Bentz, Gerald Wulf, Gerhard Held, Bernd Hertenstein, Hans Salwender, Verena I Gaidzik, Brigitte Schlegelberger, Daniela Weber, Konstanze Döhner, Arnold Ganser, Hartmut Döhner
The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m(2), days 6-8; 15 mg/m(2), days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation...
October 3, 2016: Annals of Hematology
Dongqing Guo, Ming Lu, Xihan Hu, Jiajia Xu, Guangjing Hu, Ming Zhu, Xiaowei Zhang, Qin Li, Catherine Cy Chang, Ta-Yuan Chang, Baoliang Song, Ying Xiong, Boliang Li
Acyl-coenzyme A:cholesterol acyltransferases (ACATs) are the exclusive intracellular enzymes that catalyze the formation of cholesteryl/steryl esters (CE/SE). In our previous work, we found that the high-level expression of human ACAT2 gene with the CpG hypomethylation of its whole promoter was synergistically regulated by two transcription factors Cdx2 and HNF1α in the intestine and fetal liver. Here, we first observed that the specific CpG-hypomethylated promoter was correlated with the low expression of human ACAT2 gene in monocytic cell line THP-1...
September 29, 2016: Acta Biochimica et Biophysica Sinica
Reshma Mahima Reji, Siddik Uzzaman, Berlin Grace Vm
The high mortality rate of lung cancer is highly associated with faster metastasis spread. All Trans Retinoic Acid (ATRA), being the first choice drug for leukemia therapy is now under intense study for its therapeutic efficiency in other solid cancers. This study was aimed to investigate the anti-metastasis activity of free ATRA and liposome entrapped ATRA (5:4:1) in the experimental C57BL/6 mice model developed by the injection of B16F10 cell line into the tail vein. The ATRA drug was given via i.p for 21 days...
September 27, 2016: Anti-cancer Agents in Medicinal Chemistry
Susan A Holechek, Megan S McAfee, Lizbeth M Nieves, Vanessa P Guzman, Kavita Manhas, Timothy Fouts, Kenneth Bagley, Joseph N Blattman
In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all-trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8(+) T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings...
September 23, 2016: Vaccine
J A Gil-Delgado, D Guijarro, R U Gosálvez, G M López-Iborra, A Ponz, A Velasco
Plastic intake by marine vertebrates has been widely reported, but information about its presence in continental waterfowl is scarce. Here we analyzed faeces of waterbirds species (European coot, Fulica atra, mallard, Anas platyrhynchos and shelduck, Tadorna tadorna) for plastic debris in five wetlands in Central Spain. We collected 89 faeces of shelduck distributed in four lakes, 43.8% of them presented plastic remnants. Sixty percent of 10 faeces of European coot and 45% of 40 faeces of mallard contained plastic debris...
September 22, 2016: Environmental Pollution
Lei Shi, Xiang-Qin Weng, Yan Sheng, Jing Wu, Ming Ding, Xun Cai
Although all-trans retinoic acid (ATRA) is regarded as a prominent example of differentiation therapy, it is not effective for the treatment of other subtypes of acute myeloid leukemia (AML) beyond acute promyelocytic leukemia (APL). Therefore, new strategies need to be explored to extend the efficacy of ATRA-based therapy to non-APL AML patients. In the present study, staurosporine, a protein kinase C (PKC) pan-inhibitor, exhibited synergism with ATRA to promote granulocytic differentiation in poorly ATRA-sensitive U937 cells but not in ATRA unresponsive K562 and Kasumi cells...
September 23, 2016: Oncology Reports
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