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Retinoic acid receptors

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https://www.readbyqxmd.com/read/27911385/application-of-impermeable-barriers-combined-with-candidate-factor-soaked-beads-to-study-inductive-signals-in-the-chick
#1
Susan Wilde, Malcolm P Logan
The chick embryo provides a superb vertebrate model that can be used to dissect developmental questions in a direct way. Its accessibility and robustness following surgical intervention are key experimental strengths. Mica plates were the first barriers used to prevent chick limb bud initiation(1). Protocols that use aluminum foil as an impermeable barrier to wing bud or leg bud induction and or initiation are described. We combine this technique with bead placement lateral to the barrier to exogenously supply candidate endogenous factors that have been blocked by the barrier...
November 17, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27902884/synthesis-and-biological-evaluation-of-new-triazolo-and-imidazolopyridine-ror%C3%AE-t-inverse-agonists
#2
Samuel Hintermann, Christine Guntermann, Henri Mattes, David A Carcache, Juergen Wagner, Anna Vulpetti, Andreas Billich, Janet Dawson, Klemens Kaupmann, Joerg Kallen, Rowan Stringer, David Orain
Retinoic-acid-related orphan receptor γt (RORγt) is a key transcription factor implicated in the production of pro-inflammatory Th17 cytokines, which drive a number of autoimmune diseases. Despite diverse chemical series having been reported, combining high potency with a good physicochemical profile has been a very challenging task in the RORγt inhibitor field. Based on available chemical structures and incorporating in-house knowledge, a new series of triazolo- and imidazopyridine RORγt inverse agonists was designed...
November 30, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27897208/beta-1-integrin-ligation-and-tlr-ligation-enhance-gm-csf-induced-aldh1a2-expression-in-dendritic-cells-but-differentially-regulate-their-anti-inflammatory-properties
#3
Aya Yokota-Nakatsuma, Yoshiharu Ohoka, Hajime Takeuchi, Si-Young Song, Makoto Iwata
Retinoic acid (RA)-producing CD103(+) mature dendritic cells (DCs) in mesenteric lymph nodes (MLNs) play crucial roles in gut immunity. GM-CSF and RA contribute to the expression of the RA-producing enzyme ALDH1A2. However, additional signals appeared to be required for inducing ALDH1A2(high) mature DCs from immature DCs. We found here that TLR ligands (Ls) and immobilized E-cadherin could provide such signals in FLT3-L-generated bone marrow (BM)-derived DCs after treatment with GM-CSF and the RA receptor agonist Am80...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27893937/prognostic-significance-of-equivocal-human-epidermal-growth-factor-receptor-2-results-and-clinical-utility-of-alternative-chromosome-17-genes-in-patients-with-invasive-breast-cancer-a-cohort-study
#4
Nour Sneige, Kenneth R Hess, Asha S Multani, Yun Gong, Nuhad K Ibrahim
BACKGROUND: The 2013 testing guidelines for determining the human epidermal growth factor receptor 2 (HER2) status include new cutoff points for the HER2/chromosome enumeration probe 17 (CEP17) ratio and the average HER2 copy number per cell, and they recommend using a reflex test with alternative chromosome 17 probes (Ch17Ps) to resolve equivocal HER2 results. This study sought to determine the clinical utility of alternative Ch17Ps in equivocal cases and the effects of equivocal results and/or a change in the HER2 status on patients' outcomes...
November 28, 2016: Cancer
https://www.readbyqxmd.com/read/27880037/suppressed-erythropoietin-expression-in-a-nitrofen-induced-congenital-diaphragmatic-hernia
#5
Hajime Takayasu, Koki Hagiwara, Kouji Masumoto
BACKGROUND: Erythropoietin (EPO), an essential stimulator of erythropoiesis produced by the fetal liver, is important both in vascular remodeling and modulation of the endothelial response in the pulmonary vasculature. In addition, EPO guides alveolar development, along with retinoic acid (RA). EPO is a direct target of RA, and the retinoid pathway is altered in the nitrofen-induced congenital diaphragmatic hernia (CDH) model. In the present study, we tested the hypothesis that the synthesis of EPO is suppressed in a rat model of CDH...
November 23, 2016: Pediatric Pulmonology
https://www.readbyqxmd.com/read/27879053/n-arylsulfonyl-indolines-as-retinoic-acid-receptor-related-orphan-receptor%C3%A2-%C3%AE-ror%C3%AE-agonists
#6
Christelle Doebelin, Rémi Patouret, Ruben D Garcia-Ordonez, Mi Ra Chang, Venkatasubramanian Dharmarajan, Dana S Kuruvilla, Scott J Novick, Li Lin, Michael D Cameron, Patrick R Griffin, Theodore M Kamenecka
The nuclear retinoic acid receptor-related orphan receptor γ (RORγ; NR1F3) is a key regulator of inflammatory gene programs involved in T helper 17 (TH 17) cell proliferation. As such, synthetic small-molecule repressors (inverse agonists) targeting RORγ have been extensively studied for their potential as therapeutic agents for various autoimmune diseases. Alternatively, enhancing TH 17 cell proliferation through activation (agonism) of RORγ may boost an immune response, thereby offering a potentially new approach in cancer immunotherapy...
November 23, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27865806/ikaros-exploiting-and-targeting-the-hematopoietic-stem-cell-niche-in-b-progenitor-acute-lymphoblastic-leukemia
#7
REVIEW
Michelle L Churchman, Charles G Mullighan
Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high risk B-progenitor ALL such as BCR-ABL1 positive (Ph+) and Ph-like ALL, and are associated with poor outcome, even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors in the treatment of Ph+ ALL. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiating, skewing lineage of leukemia from myeloid to lymphoid, and in Ph+ leukemia, conferring resistance to TKI therapy without abrogating ABL1 inhibition...
November 16, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27863906/post-translational-control-of-intracellular-pathogen-sensing-pathways
#8
REVIEW
Cindy Chiang, Michaela U Gack
Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes...
November 15, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27862498/all-trans-retinoic-acid-preconditioning-enhances-proliferation-angiogenesis-and-migration-of-mesenchymal-stem-cell-in-vitro-and-enhances-wound-repair-in-vivo
#9
M Pourjafar, M Saidijam, K Mansouri, H Ghasemibasir, F Karimi Dermani, R Najafi
OBJECTIVES: Stem cell therapy is considered to be a suitable alternative in treatment of a number of diseases. However, there are challenges in their clinical application in cell therapy, such as to reduce survival and loss of transplanted stem cells. It seems that chemical and pharmacological preconditioning enhances their therapeutic efficacy. In this study, we investigated effects of all-trans retinoic acid (ATRA) on survival, angiogenesis and migration of mesenchymal stem cells (MSCs) in vitro and in a wound-healing model...
November 10, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27862268/novel-protective-role-of-nuclear-melatonin-receptor-ror%C3%AE-in-diabetic-cardiomyopathy
#10
Yichao Zhao, Longwei Xu, Song Ding, Nan Lin, Qingqi Ji, Lingchen Gao, Yuanyuan Su, Jun Pu, Ben He
Diabetic cardiomyopathy is a major complication that significantly contributes to morbidity and mortality in diabetics with few therapies. Moreover, anti-diabetic drugs reported inconsistent or even adverse cardiovascular effects, suggesting it is important to exploit novel therapeutic targets against diabetic cardiomyopathy. Here, we observed that the nuclear melatonin receptor, the retinoic acid-related orphan receptor α (RORα), was downregulated in diabetic hearts. By utilizing a mouse line with RORα disruption, we demonstrated that RORα deficiency led to significantly augmented diastolic dysfunction and cardiac remodeling induced by diabetes...
November 18, 2016: Journal of Pineal Research
https://www.readbyqxmd.com/read/27861498/somite-derived-retinoic-acid-regulates-zebrafish-hematopoietic-stem-cell-formation
#11
Laura M Pillay, Kacey J Mackowetzky, Sonya A Widen, Andrew Jan Waskiewicz
Hematopoietic stem cells (HSCs) are multipotent progenitors that generate all vertebrate adult blood lineages. Recent analyses have highlighted the importance of somite-derived signaling factors in regulating HSC specification and emergence from dorsal aorta hemogenic endothelium. However, these factors remain largely uncharacterized. We provide evidence that the vitamin A derivative retinoic acid (RA) functions as an essential regulator of zebrafish HSC formation. Temporal analyses indicate that RA is required for HSC gene expression prior to dorsal aorta formation, at a time when the predominant RA synthesis enzyme, aldh1a2, is strongly expressed within the paraxial mesoderm and somites...
2016: PloS One
https://www.readbyqxmd.com/read/27853642/rig-i-activation-induces-the-release-of-extracellular-vesicles-with-antitumor-activity
#12
Juliane Daßler-Plenker, Katrin S Reiners, Jasper G van den Boorn, Hinrich P Hansen, Bastian Putschli, Sabine Barnert, Christine Schuberth-Wagner, Rolf Schubert, Thomas Tüting, Michael Hallek, Martin Schlee, Gunther Hartmann, Elke Pogge von Strandmann, Christoph Coch
Activation of the innate immune receptor retinoic acid-inducible gene I (RIG-I) by its specific ligand 5'-triphosphate-RNA (3pRNA) triggers antitumor immunity predominantly via NK cell activation and direct apoptosis induction in tumor cells. However, how NK cells are mobilized to attack the tumor cells remains elusive. Here, we show that RIG-I activation induced the secretion of extracellular vesicles (EVs) from melanoma cells, which by themselves revealed antitumor activity in vitro and in vivo. RIG-I-induced EVs from melanoma cells exhibited an increased expression of the NKp30-ligand (BAG6, BAT3) on their surface triggering NK cell-mediated lysis of melanoma cells via activation of the cytotoxicity NK cell-receptor NKp30...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27852111/ror%C3%AE-t-inhibitors-as-potential-back-ups-for-the-phase-ii-candidate-vtp-43742-from-vitae-pharmaceuticals-patent-evaluation-of-wo2016061160-and-us20160122345
#13
Christian Gege
Retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt or RORc2) is a key transcription factor for the differentiation of naïve proinflammatory CD4(+) T cells and the production of T helper-17 (TH17) cells. Inhibiting RORγt activity is thought to be beneficial in targeting a variety of inflammatory and autoimmune disorders. Recently Vitae Pharmaceuticals (to be acquired by Allergan) reported positive top-line results from a Phase 2a clinical trial of RORγt inhibitor VTP-43742 in psoriatic patients...
November 17, 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27835617/hiv-persists-in-ccr6-cd4-t-cells-from-colon-and-blood-during-antiretroviral-therapy
#14
Annie Gosselin, Tomas Raul Wiche Salinas, Delphine Planas, Vanessa S Wacleche, Yuwei Zhang, Rémi Fromentin, Nicolas Chomont, Éric A Cohen, Barbara Shacklett, Vikram Mehraj, Maged P Ghali, Jean-Pierre Routy, Petronela Ancuta
OBJECTIVES: The objective of this article is to investigate the contribution of colon and blood CD4 T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during antiretroviral therapy. DESIGN: Matched sigmoid biopsies and blood samples (n = 13) as well as leukapheresis (n = 20) were collected from chronically HIV-infected individuals receiving antiretroviral therapy. Subsets of CD4 T cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA), central memory (TCM; CD45RACCR7), effector (TEM/TM; CD45RACCR7), Th17 (CCR6CCR4), Th1Th17 (CCR6CXCR3), Th1 (CCR6CXCR3), and Th2 (CCR6CCR4)...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27832522/combined-treatments-with-a-retinoid-receptor-agonist-and-epigenetic-modulators-in-human-neuroblastoma-cells
#15
Viviane Rösner Almeida, Igor Araujo Vieira, Marienela Buendia, André Tesainer Brunetto, Lauro J Gregianin, Algemir Lunardi Brunetto, Fábio Klamt, Caroline Brunetto de Farias, Ana Lucia Abujamra, Patrícia Luciana da Costa Lopez, Rafael Roesler
Neuroblastoma (NB) is the most common extracranial solid childhood tumor accounting for around 15% of pediatric cancer deaths and most probably originates from a failure in the development of embryonic neural crest cells. Retinoids can inhibit the proliferation and stimulate differentiation of NB cells. In addition, epigenetic events involving changes in chromatin structure and DNA methylation can mediate the effects of retinoids; hence, the scope of this study is to investigate the use of retinoids and epigenetic drugs in NB cell lines...
November 10, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27830505/non-classical-transcriptional-activity-of-retinoic-acid
#16
Noa Noy
It has long been established that the transcriptional activity of retinoic acid (RA) is mediated by members of the nuclear receptor family of ligand-activated transcription factors termed RA receptors (RARs). More recent observations have established that RA also activates an additional nuclear receptor, PPARβ/δ. Partitioning RA between RARs and PPARβ/δ is governed by different intracellular lipid-binding proteins: cellular RA binding protein 2 (CRABP2) delivers RA to nuclear RARs and a fatty acid binding protein (FABP5) delivers the hormone from the cytosol to nuclear PPARβ/δ...
2016: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/27830504/cellular-retinoic-acid-binding-proteins-genomic-and-non-genomic-functions-and-their-regulation
#17
Li-Na Wei
Cellular retinoic acid binding proteins (CRABPs) are high-affinity retinoic acid (RA) binding proteins that mainly reside in the cytoplasm. In mammals, this family has two members, CRABPI and II, both highly conserved during evolution. The two proteins share a very similar structure that is characteristic of a "β-clam" motif built up from10-strands. The proteins are encoded by two different genes that share a very similar genomic structure. CRABPI is widely distributed and CRABPII has restricted expression in only certain tissues...
2016: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/27830500/functions-of-intracellular-retinoid-binding-proteins
#18
Joseph L Napoli
Multiple binding and transport proteins facilitate many aspects of retinoid biology through effects on retinoid transport, cellular uptake, metabolism, and nuclear delivery. These include the serum retinol binding protein sRBP (aka Rbp4), the plasma membrane sRBP receptor Stra6, and the intracellular retinoid binding-proteins such as cellular retinol-binding proteins (CRBP) and cellular retinoic acid binding-proteins (CRABP). sRBP transports the highly lipophilic retinol through an aqueous medium. The major intracellular retinol-binding protein, CRBP1, likely enhances efficient retinoid use by providing a sink to facilitate retinol uptake from sRBP through the plasma membrane or via Stra6, delivering retinol or retinal to select enzymes that generate retinyl esters or retinoic acid, and protecting retinol/retinal from excess catabolism or opportunistic metabolism...
2016: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/27822424/nuclear-tblr1-as-an-er-corepressor-promotes-cell-proliferation-migration-and-invasion-in-breast-and-ovarian-cancer
#19
Xinyu Wu, Yang Zhan, Xin Li, Jianjun Wei, Larion Santiago, Garrett Daniels, Fangming Deng, Xuelin Zhong, Luis Chiriboga, Ross Basch, Sheng Xiong, Yan Dong, Xinmin Zhang, Peng Lee
Estrogen receptors (ER) play important roles in the development and progression of breast and ovarian cancers. ERs mediate transcriptional regulation through interaction with cofactors and binding to response elements within the regulatory elements of target genes. Here, we examined the expression and function of TBLR1/TBL1XR1, a core component of NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid receptor) corepressor complexes, in breast and ovarian cancers. We found that although TBLR1 is present in both the nucleus and cytoplasm of normal and neoplastic breast and ovarian cells, it is expressed at significantly higher levels in the nucleus of malignant breast and ovarian cells compared to benign cells...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27821666/duck-tembusu-virus-nonstructural-protein-1-antagonizes-ifn-%C3%AE-signaling-pathways-by-targeting-visa
#20
Junyong Wang, Cao-Qi Lei, Yanhong Ji, Hongbo Zhou, Yujie Ren, Qianqian Peng, Yan Zeng, Yane Jia, Jinying Ge, Bo Zhong, Yu Li, Jianzhong Wei, Hong-Bing Shu, Qiyun Zhu
Duck Tembusu virus (DTMUV) is an emergent infectious pathogen that has caused severe disease in ducks and huge economic losses to the poultry industry in China since 2009. Previously, we showed that DTMUV inhibits IFN-β induction early in infection; however, the mechanisms of the inhibition of innate immune responses remain poorly understood. In this study, we screened DTMUV-encoded structural and nonstructural proteins using reporter assays and found that DTMUV NS1 markedly suppressed virus-triggered IFN-β expression by inhibiting retinoic acid-inducible gene I-like receptor signaling...
November 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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