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https://www.readbyqxmd.com/read/28300669/enhanced-plasma-protein-carbonylation-in-patients-with-myelodysplastic-syndromes
#1
Alžběta Hlaváčková, Jana Štikarová, Kristýna Pimková, Leona Chrastinová, Pavel Májek, Roman Kotlín, Jaroslav Čermák, Jiří Suttnar, Jan Evangelista Dyr
Myelodysplastic syndromes (MDS) represent a heterogeneous group of pre-leukemic disorders, characterized by ineffective hematopoiesis and the abnormal blood cell development of one or more lineages. Oxidative stress, as an important factor in the carcinogenesis of onco-hematological diseases, is also one of the known factors involved in the pathogenesis of MDS. An increase of reactive oxygen species (ROS) may lead to the oxidation of DNA, lipids, and proteins, thereby causing cell damage. Protein carbonylation caused by ROS is defined as an irreversible post-translational oxidative modification of amino acid side chains, and could play an important role in signaling processes...
March 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28300567/9-cis-retinoic-acid-modulates-myotrophin-expression-and-its-mir-in-physiological-and-pathophysiological-cell-models
#2
Mariarita Perri, Maria Cristina Caroleo, Nannan Liu, Luca Gallelli, Giovambattista De Sarro, Hiroyuki Kagechika, Erika Cione
Functional studies indicate that essential cellular processes are controlled by Vitamin A derivatives. Among these the retinoic acid isoforms, all-trans- and 9-cis (9cRA), regulate the expression of various genes in both physiological and pathological conditions. Using several in vitro experimental models such as pancreatic β-cells, pre-adipocytes and breast cancer cells with different phenotypes, we demonstrated the capability of 9cRA to modulate myotrophin (Mtpn) and miR-375 expressions. The 9cRA effect in pancreatic β-cells line INS-1 832/13 point out a decreased expression of Mptn at both mRNA and protein levels associated to a concomitant increase of miR-375...
March 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28283063/systemic-human-ilc-precursors-provide-a-substrate-for-tissue-ilc-differentiation
#3
Ai Ing Lim, Yan Li, Silvia Lopez-Lastra, Ralph Stadhouders, Franziska Paul, Armanda Casrouge, Nicolas Serafini, Anne Puel, Jacinta Bustamante, Laura Surace, Guillemette Masse-Ranson, Eyal David, Helene Strick-Marchand, Lionel Le Bourhis, Roberto Cocchi, Davide Topazio, Paolo Graziano, Lucia Anna Muscarella, Lars Rogge, Xavier Norel, Jean-Michel Sallenave, Matthieu Allez, Thomas Graf, Rudi W Hendriks, Jean-Laurent Casanova, Ido Amit, Hans Yssel, James P Di Santo
Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCPs). How ILCPs give rise to mature tissue-resident ILCs remains unclear. Here, we identify circulating and tissue ILCPs in humans that fail to express the transcription factors and cytokine outputs of mature ILCs but have these signature loci in an epigenetically poised configuration. Human ILCPs robustly generate all ILC subsets in vitro and in vivo. While human ILCPs express low levels of retinoic acid receptor (RAR)-related orphan receptor C (RORC) transcripts, these cells are found in RORC-deficient patients and retain potential for EOMES(+) natural killer (NK) cells, interferon gamma-positive (IFN-γ(+)) ILC1s, interleukin (IL)-13(+) ILC2s, and for IL-22(+), but not for IL-17A(+) ILC3s...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28274610/retinoic-acid-signaling-is-dispensable-for-somatic-development-and-function-in-the-mammalian-ovary
#4
Anna Minkina, Robin E Lindeman, Micah D Gearhart, Anne-Amandine Chassot, Marie-Christine Chaboissier, Norbert B Ghyselinck, Vivian J Bardwell, David Zarkower
Retinoic acid (RA) is a potent inducer of cell differentiation and plays an essential role in sex-specific germ cell development in the mammalian gonad. RA is essential for male gametogenesis and hence fertility. However, RA can also disrupt sexual cell fate in somatic cells of the testis, promoting transdifferentiation of male Sertoli cells to female granulosa-like cells when the male sexual regulator Dmrt1 is absent. The feminizing ability of RA in the Dmrt1 mutant somatic testis suggests that RA might normally play a role in somatic cell differentiation or cell fate maintenance in the ovary...
March 6, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28261972/balanced-covariates-with-response-adaptive-randomization
#5
Benjamin R Saville, Scott M Berry
Response adaptive randomization (RAR) methods for clinical trials are susceptible to imbalance in the distribution of influential covariates across treatment arms. This can make the interpretation of trial results difficult, because observed differences between treatment groups may be a function of the covariates and not necessarily because of the treatments themselves. We propose a method for balancing the distribution of covariate strata across treatment arms within RAR. The method uses odds ratios to modify global RAR probabilities to obtain stratum-specific modified RAR probabilities...
March 6, 2017: Pharmaceutical Statistics
https://www.readbyqxmd.com/read/28254518/effect-of-modeled-microgravity-on-radiation-induced-adaptive-response-of-root-growth-in-arabidopsis-thaliana
#6
Chenguang Deng, Ting Wang, Jingjing Wu, Wei Xu, Huasheng Li, Min Liu, Lijun Wu, Jinying Lu, Po Bian
Space particles have an inevitable impact on organisms during space missions; radio-adaptive response (RAR) is a critical radiation effect due to both low-dose background and sudden high-dose radiation exposure during solar storms. Although it is relevant to consider RAR within the context of microgravity, another major space environmental factor, there is no existing evidence as to its effects on RAR. In the present study, we established an experimental method for detecting the effects of gamma-irradiation on the primary root growth of Arabidopsis thaliana, in which RAR of root growth was significantly induced by several dose combinations...
February 2017: Mutation Research
https://www.readbyqxmd.com/read/28253328/reprogramming-of-the-retinoic-acid-pathway-in-decidualizing-human-endometrial-stromal-cells
#7
Rie Ozaki, Keiji Kuroda, Yuko Ikemoto, Asako Ochiai, Akemi Matsumoto, Jun Kumakiri, Mari Kitade, Atsuo Itakura, Joanne Muter, Jan J Brosens, Satoru Takeda
Upon breaching of the endometrial surface epithelium, the implanting embryo embeds in the decidualizing stroma. Retinoic acid (RA), a metabolite of vitamin A, is an important morphogen during embryonic and fetal development, although the role of the RA pathway in the surrounding decidual cells is not understood. Here we show that decidual transformation of human endometrial stromal cells (HESCs) results in profound reprogramming of the RA signaling and metabolism pathways. Differentiating HESCs downregulate the intracellular carrier proteins CRABP2 and FABP5, responsible for transfer and binding of RA to the nuclear receptors RAR and PPARβ/δ, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28250025/synthesis-of-apo-13-and-apo-15-lycopenoids-cleavage-products-of-lycopene-that-are-retinoic-acid-antagonists
#8
Sureshbabu Narayanasamy, Jian Sun, Ryan E Pavlovicz, Abdulkerim Eroglu, Cassandra E Rush, Benjamin D Sunkel, Chenglong Li, Earl H Harrison, Robert W Curley
Consumption of the tomato carotenoid, lycopene, has been associated with favorable health benefits. Some of lycopenes biological activity may be due to metabolites resulting from cleavage of the lycopene molecule. Because of their structural similarity to the retinoic acid receptor antagonist beta-apo-13-carotenone, the first half putative oxidative cleavage products of the symmetrical lycopene have been synthesized. All transformations proceed in moderate to good yield and some with high stereochemical integrity allowing ready access to these otherwise difficult to obtain terpenoids...
March 1, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28244006/neurogenesis-in-response-to-synthetic-retinoids-at-different-temporal-scales
#9
Hesham Haffez, Thabat Khatib, Peter McCaffery, Stefan Przyborski, Christopher Redfern, Andrew Whiting
All-trans retinoic acid (ATRA) plays key roles in neurogenesis mediated by retinoic acid receptors (RARs). RARs are important targets for the therapeutic regulation of neurogenesis but effective drug development depends on modelling-based strategies to design high-specificity ligands in combination with good biological assays to discriminate between target-specificity and off-target effects. Using neuronal differentiation as a model, the aim of this study was to test the hypothesis that responses across different temporal scales and assay platforms can be used as comparable measures of retinoid activity...
February 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28230720/role-of-vitamin-a-retinoic-acid-in-regulation-of-embryonic-and-adult-hematopoiesis
#10
REVIEW
Ana Cañete, Elena Cano, Ramón Muñoz-Chápuli, Rita Carmona
Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality...
February 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28224666/refinement-and-cross-validation-of-nickel-bioavailability-in-pnec-pro-a-regulatory-tool-for-site-specific-risk-assessment-of-metals-in-surface-water
#11
Anja J Verschoor, Martina G Vijver, Jos P M Vink
The European Water Framework Directive prescribes that the environmental quality standards for nickel in surface waters should be based on bioavailable concentrations. Biotic ligand models (BLMs) are powerful tools to account for site-specific bioavailability within risk assessments. Several BLMs and simplified tools are available. For nickel, most of them are based on the same toxicity dataset and chemical speciation methodology as laid down in the 2008 European Union Environmental-Risk Assessment Report (RAR)...
February 22, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28223944/il-1%C3%AE-induced-downregulation-of-the-multifunctional-pdz-adaptor-pdzk1-is-attenuated-by-erk-inhibition-rxr%C3%AE-or-ppar%C3%AE-stimulation-in-enterocytes
#12
Min Luo, Sunil Yeruva, Yongjian Liu, Giriprakash Chodisetti, Brigitte Riederer, Manoj B Menon, Keisuke Tachibana, Takefumi Doi, Ursula E Seidler
Background: The PDZ adaptor protein PDZK1 modulates the membrane expression and function of a variety of intestinal receptors and ion/nutrient transporters. Its expression is strongly decreased in inflamed intestinal mucosa of mice and IBD patients. Aim and Methods: We investigated whether the inflammation-associated PDZK1 downregulation is a direct consequence of proinflammatory cytokine release by treating intestinal Caco-2BBE cells with TNF-α, IFN-γ, and IL-1β, and analysing PDZK1 promotor activity, mRNA and protein expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28216044/radiolabeling-and-initial-biological-evaluation-of-18-f-kbm-1-for-imaging-rar-%C3%AE-receptors-in-neuroblastoma
#13
Kiran Kumar Solingapuram Sai, Bhaskar C Das, Anirudh Sattiraju, Frankis G Almaguel, Suzanne Craft, Akiva Mintz
Retinoic acid receptor alpha (RAR-α) plays a significant role in a number of diseases, including neuroblastoma. Children diagnosed with high-risk neuroblastoma are treated13-cis-retinoic acid, which reduces risk of cancer recurrence. Neuroblastoma cell death is mediated via RAR-α, and expression of RAR-α is upregulated after treatment. A molecular imaging probe that binds RAR-α will help clinicians to diagnose and stratify risk for patients with neuroblastoma, who could benefit from retinoid-based therapy...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28188970/refractory-anemia-with-ring-sideroblasts-rars-and-rars-with-thrombocytosis-rars-t-2017-update-on-diagnosis-risk-stratification-and-management
#14
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T). DIAGNOSIS: MDS-RS is a lower risk MDS, with single or multilineage dysplasia (SLD/MLD), <5% bone marrow (BM) blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations)...
March 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28186459/bioactivity-of-carotenoids-chasms-of-knowledge
#15
Torsten Bohn
Carotenoid dietary intake, especially within fruits/vegetables and their plasma levels have been associated in many epidemiological studies with a reduced risk of several chronic diseases, including type-2 diabetes, cardiovascular diseases, several types of cancer, and agerelated macular degeneration. However, intervention trials with isolated carotenoids (as supplements) have fallen short of fulfi lling the hopes that were placed in these lipophilic pigments, often producing no positive or even adverse effects, such as increased lung cancer rate or total mortality...
February 10, 2017: International Journal for Vitamin and Nutrition Research. Journal International de Vitaminologie et de Nutrition
https://www.readbyqxmd.com/read/28161411/structural-basis-for-the-inhibition-of-akr1b10-by-the-c3-brominated-ttnpb-derivative-uvi2008
#16
Francesc X Ruiz, Isidro Crespo, Susana Álvarez, Sergio Porté, Joan Giménez-Dejoz, Alexandra Cousido-Siah, André Mitschler, Ángel R de Lera, Xavier Parés, Alberto Podjarny, Jaume Farrés
UVI2008, a retinoic acid receptor (RAR) β/γ agonist originated from C3 bromine addition to the parent RAR pan-agonist 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB), is also a selective inhibitor of aldo-keto reductase family member 1B10 (AKR1B10). Thus, it might become a lead drug for the design of compounds targeting both activities, as an AKR1B10 inhibitor and RAR agonist, which could constitute a novel therapeutic approach against cancer and skin-related diseases...
February 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28152413/over-expression-of-cd200-predicts-poor-prognosis-in-mds
#17
Jia-Xi Chen, Li-Ping Mei, Bao-Guo Chen, Dong-Lian Wang, Wen-da Luo, Li-Fei Luo, Ruyue Lu, Rui Zheng, Li Zhang
BACKGROUND: We studied the expression of CD200 in a series of 101 patients with diagnosis of myelodysplastic syndrome (MDS), to evaluate its impact on outcome and its possible association with other known prognostic factors. MATERIAL/METHODS: The CD200 was detected by flow cytometry, and the chromosome karyotypes were determined by G banding respectively. The Mann-Whitney U test was used to analyze the association among CD200 expression and clinical features. In addition, the overall survival and AML transformation of the MDS patients according to the expression level of CD200 was also explored...
January 15, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28132904/cellular-retinoid-binding-proteins-crbp-crabp-fabp5-effects-on-retinoid-metabolism-function-and-related-diseases
#18
REVIEW
Joseph L Napoli
Cellular binding-proteins (BP), including CRBP1, CRBP2, CRABP1, CRABP2, and FABP5, shepherd the poorly aqueous soluble retinoids during uptake, metabolism and function. Holo-BP promote efficient use of retinol, a scarce but essential nutrient throughout evolution, by sheltering it and its major metabolite all-trans-retinoic acid from adventitious interactions with the cellular milieu, and by imposing specificity of delivery to enzymes, nuclear receptors and other partners. Apo-BP reflect cellular retinoid status and modify activities of retinoid metabolon enzymes, or exert non-canonical actions...
January 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28125680/allosteric-regulation-in-the-ligand-binding-domain-of-retinoic-acid-receptor%C3%AE
#19
Yassmine Chebaro, Serena Sirigu, Ismail Amal, Régis Lutzing, Roland H Stote, Cécile Rochette-Egly, Natacha Rochel, Annick Dejaegere
Retinoic acid (RA) plays key roles in cell differentiation and growth arrest through nuclear retinoic acid receptors (RARs), which are ligand-dependent transcription factors. While the main trigger of RAR activation is the binding of RA, phosphorylation of the receptors has also emerged as an important regulatory signal. Phosphorylation of the RARγ N-terminal domain (NTD) is known to play a functional role in neuronal differentiation. In this work, we investigated the phosphorylation of RARγ ligand binding domain (LBD), and present evidence that the phosphorylation status of the LBD affects the phosphorylation of the NTD region...
2017: PloS One
https://www.readbyqxmd.com/read/28115699/similarities-and-differences-in-the-transcriptional-control-of-expression-of-the-mouse-tslp-gene-in-skin-epidermis-and-intestinal-epithelium
#20
Krishna Priya Ganti, Atish Mukherji, Milan Surjit, Mei Li, Pierre Chambon
We previously reported that selective ablation of the nuclear receptors retinoid X receptor (RXR)-α and RXR-β in mouse epidermal keratinocytes (RXR-αβ(ep-/-)) or a topical application of active vitamin D3 (VD3) and/or all-trans retinoic acid (RA) on wild-type mouse skin induces a human atopic dermatitis-like phenotype that is triggered by an increased expression of the thymic stromal lymphopoietin (TSLP) proinflammatory cytokine. We demonstrate here that in epidermal keratinocytes, unliganded heterodimers of vitamin D receptor (VDR)/RXR-α and retinoic acid receptor-γ (RAR-γ)/RXR-β are bound as repressing complexes to their cognate DNA-binding sequence(s) (DBS) in the TSLP promoter regulatory region...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
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