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Retinoid X Receptor

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https://www.readbyqxmd.com/read/29319225/de-novo-design-of-bioactive-small-molecules-by-artificial-intelligence
#1
Daniel Merk, Lukas Friedrich, Francesca Grisoni, Gisbert Schneider
Generative artificial intelligence offers a fresh view on molecular design. We present the first-time prospective application of a deep learning model for designing new druglike compounds with desired activities. For this purpose, we trained a recurrent neural network to capture the constitution of a large set of known bioactive compounds represented as SMILES strings. By transfer learning, this general model was fine-tuned on recognizing retinoid X and peroxisome proliferator-activated receptor agonists. We synthesized five top-ranking compounds designed by the generative model...
January 10, 2018: Molecular Informatics
https://www.readbyqxmd.com/read/29305858/identification-of-a-candidate-enhancer-for-dmrt3-involved-in-spastic-cerebral-palsy-pathogenesis
#2
Naoto Kubota, Toshifumi Yokoyama, Nobuhiko Hoshi, Mikita Suyama
Cerebral palsy (CP) is a major neuronal disease and the most common movement disorder in children. Although environmental factors leading to CP have been greatly investigated, the genetic mechanism underlying CP is not well understood. Here we focused on two clinical reports that characterized a deletion involving the KANK1 gene locus in the 9p24.3 region. One report shows spastic CP and the other shows no spastic CP phenotype. Based on the epigenetic status and evolutionary conservation, we first found a functional genomic element at the noncoding region that was deleted only in patients with spastic CP...
January 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29300860/examination-of-vdr-rxr-drip205-interaction-intranuclear-localization-and-dna-binding-in-ras-transformed-keratinocytes-and-its-implication-for-designing-optimal-vitamin-d-therapy-in-cancer
#3
Sylvester Jusu, John F Presley, Chris Williams, Sanjoy Kumar Das, Bertrand Jean-Claude, Richard Kremer
RXR occupies a central position within the nuclear receptor superfamily serving as an obligatory partner to numerous other nuclear receptors including VDR. In the present study, we examined whether phosphorylation of RXRalpha at serine 260 affects VDR/RXR and DRIP205 coactivator recruitment, interactions and binding of the VDR/ hRXRα /DRIP205 complex to chromatin. Serine 260 is a critical amino acid on the human retinoid X receptor alpha (hRXRα) that is located in close spatial proximity to regions of coactivator and corepressor interactions...
December 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/29286311/comparative-proteomics-analysis-of-urine-reveals-down-regulation-of-acute-phase-response-signaling-and-lxr-rxr-activation-pathways-in-prostate-cancer
#4
Katarina Davalieva, Sanja Kiprijanovska, Ivana Maleva Kostovska, Sotir Stavridis, Oliver Stankov, Selim Komina, Gordana Petrusevska, Momir Polenakovic
Detecting prostate cancer (PCa) using non-invasive diagnostic markers still remains a challenge. The aim of this study was the identification of urine proteins that are sufficiently sensitive and specific to detect PCa in the early stages. Comparative proteomics profiling of urine from patients with PCa, benign prostate hyperplasia, bladder cancer, and renal cancer, coupled with bioinformatics analysis, were performed. Statistically significant difference in abundance showed 20 and 85 proteins in the 2-D DIGE/MS and label-free LC-MS/MS experiments, respectively...
December 29, 2017: Proteomes
https://www.readbyqxmd.com/read/29286303/disturbed-vitamin-a-metabolism-in-non-alcoholic-fatty-liver-disease-nafld
#5
REVIEW
Ali Saeed, Robin P F Dullaart, Tim C M A Schreuder, Hans Blokzijl, Klaas Nico Faber
Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A's functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs)...
December 29, 2017: Nutrients
https://www.readbyqxmd.com/read/29286069/a-16-gene-expression-signature-to-distinguish-stage%C3%A2-i-from-stage%C3%A2-ii-lung-squamous-carcinoma
#6
Rui Wang, Yuxing Cai, Baoping Zhang, Zhengxia Wu
The present study aimed to perform screening of a gene signature for the discrimination and prognostic prediction of stage I and II lung squamous carcinoma. A microarray meta‑analysis was performed to identify differentially expressed genes (DEGs) between stage I and II lung squamous carcinoma samples in seven microarray datasets collected from the Gene Expression Omnibus database via the MetaQC and MetaDE package in R. The important DEGs were selected according to the betweenness centrality value of the protein‑protein interaction (PPI) network...
December 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29228308/rxr%C3%AE-enriched-cancer-stem-cell-like-properties-triggered-by-cddp-in-head-and-neck-squamous-cell-carcinoma-hnscc
#7
Pan Jiang, Chaoqi Xu, Ming Zhou, Huaqun Zhou, Weida Dong, Xiaoyue Wu, Aochang Chen, Qing Feng
Retinoid X receptor-α (RXRα) is a kind of nuclear receptor and is a target of cancer prevention and treatment in various types of cancers. Cancer stem cells (CSCs) are regarded as the main cause of carcinoma metastasis, tumor recurrence and chemotherapy resistance. So far, the mechanism how RXRα regulates CSCs remains unknown. In the present study, we found that RXRα was up-regulated in head and neck squamous cell carcinoma (HNSCC) tissues and the enriched HNSCC cancer stem cells. Over-expression of RXRα was able to expand the CSC-like properties in HNSCC cells, while knockdown of RXRα could repress the stemness respectively...
December 6, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29221723/effects-of-thyroxine-on-expression-of-proteins-related-to-thyroid-hormone-functions-tr-%C3%AE-tr-%C3%AE-rxr-and-erk1-2-in-uterus-during-peri-implantation-period
#8
Abu Sadat Md Sayem, Nelli Giribabu, Sekaran Muniandy, Naguib Salleh
INTRODUCTION: Thyroid hormone is known to play important role during embryo implantation, however mechanisms underlying its actions in uterus during peri-implantation period has not been fully identified. In this study, we hypothesized that thyroid hormone could affect expression of proteins related to its function, where these could explain mechanisms for its action in uterus during this period. METHODS: Female rats, once rendered hypothyroid via oral administration of methimazole (0...
December 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29212711/ppar%C3%AE-activation-by-bexarotene-promotes-neuroprotection-by-restoring-bioenergetic-and-quality-control-homeostasis
#9
Audrey S Dickey, Dafne N Sanchez, Martin Arreola, Kunal R Sampat, Weiwei Fan, Nicolas Arbez, Sergey Akimov, Michael J Van Kanegan, Kohta Ohnishi, Stephen K Gilmore-Hall, April L Flores, Janice M Nguyen, Nicole Lomas, Cynthia L Hsu, Donald C Lo, Christopher A Ross, Eliezer Masliah, Ronald M Evans, Albert R La Spada
Neurons must maintain protein and mitochondrial quality control for optimal function, an energetically expensive process. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that promote mitochondrial biogenesis and oxidative metabolism. We recently determined that transcriptional dysregulation of PPARδ contributes to Huntington's disease (HD), a progressive neurodegenerative disorder resulting from a CAG-polyglutamine repeat expansion in the huntingtin gene. We documented that the PPARδ agonist KD3010 is an effective therapy for HD in a mouse model...
December 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29188497/bexarotene-a-selective-rxr%C3%AE-agonist-reverses-hypotension-associated-with-inflammation-and-tissue-injury-in-a-rat-model-of-septic-shock
#10
Bahar Tunctan, Sefika P Kucukkavruk, Meryem Temiz-Resitoglu, Demet S Guden, Ayse N Sari, Seyhan Sahan-Firat
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that can activate or inhibit the expression of many target genes by forming a heterodimer complex with the retinoid X receptor (RXR). The aim of this study was to investigate effects of bexarotene, a selective RXRα agonist, on the changes in renal, cardiac, hepatic, and pulmonary expression/activity of inducible nitric oxide synthase (iNOS) and cytochrome P450 (CYP) 4F6 in relation to PPARα/β/γ-RXRα heterodimer formation in a rat model of septic shock...
November 29, 2017: Inflammation
https://www.readbyqxmd.com/read/29149247/quantitative-proteomic-profiling-of-bovine-follicular-fluid-during-follicle-development
#11
Rodrigo de Andrade Ferrazza, Elizabeth Moreira Dos Santos Schmidt, Monika Mihm Carmichael, Fabiana Ferreira de Souza, Richard Burchmore, Roberto Sartori, Peter David Eckersall, João Carlos Pinheiro Ferreira
Bovine follicular fluid (FF) constitutes the microenvironment of follicles and includes various biologically active proteins. We performed a study involving 18 healthy non-lactating Holstein cows to determine the protein expression profile of FF at key-stages of follicular development. Follicles were individually aspirated in vivo at pre-deviation (F1∼7.0mm); deviation (F1∼8.5mm); post-deviation (F1∼12.0mm); and pre-ovulatory stages of follicle development, which were confirmed by measurement of follicular estradiol and progesterone concentrations...
November 15, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29145837/molecular-network-based-analysis-of-the-mechanism-of-liver-injury-induced-by-volatile-oils-from-artemisiae-argyi-folium
#12
Hongjie Liu, Sha Zhan, Yan Zhang, Yan Ma, Liang Chen, Lingxiu Chen, Hanqiu Dong, Min Ma, Zhe Zhang
BACKGROUND: Volatile oils from Artemisiae argyi folium (VOAAF) is reported with hepatotoxicity, but the underlying mechanism is still unclear. METHODS: In the present study this molecular mechanism was explored with the Ingenuity Pathway Analysis (IPA). The chemical components of the VOAAF were searched in the database, and their target proteins were all identified in the PubChem, while drug-induced liver injury (DILI) genes were searched in the PubMed gene databases...
November 16, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#13
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29133527/interaction-of-the-phosphorylated-dna-binding-domain-in-nuclear-receptor-car-with-its-ligand-binding-domain-regulates-car-activation
#14
Ryota Shizu, Jungki Min, Mack Sobhany, Lars C Pedersen, Shingo Mutoh, Masahiko Negishi
The nuclear protein constitutive active/androstane receptor (CAR or NR1I3) regulates several liver functions such as drug and energy metabolism and cell growth or death, which are often involved in the development of diseases such as diabetes and hepatocellular carcinoma. CAR undergoes a conversion from inactive homodimers to active heterodimers with retinoid X receptor alpha (RXRα), and phosphorylation of the DNA-binding domain (DBD) at Thr-38 in CAR regulates this conversion. Here, we uncovered the molecular mechanism by which this phosphorylation regulates the intramolecular interaction between CARs DBD and ligand-binding domain (LBD), enabling the homodimer-heterodimer conversion...
November 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29128212/liver-proteomic-analysis-of-postpartum-holstein-cows-exposed-to-heat-stress-or-cooling-conditions-during-the-dry-period
#15
Amy L Skibiel, Maya Zachut, Bruno C do Amaral, Yishai Levin, Geoffrey E Dahl
Heat stress negatively affects cow performance, compromises immune function, and increases susceptibility to metabolic disorders, particularly during the dry period and as cows transition from gestation to lactation. Metabolic adaptations of the liver are critical for successful transition, yet it is unclear how heat stress affects metabolic pathways within the liver at the proteomic level. The objective of this study was to investigate the liver proteome of postpartum cows that were cooled or heat stressed during the dry period to gain insight into how protein expression is altered by prior heat stress and may contribute to performance and disease outcomes...
November 8, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29127736/liver-x-receptor-activation-inhibits-sglt2-mediated-glucose-transport-in-human-renal-proximal-tubular-cells
#16
Pattira Chonlaket, Teerasak Wongwan, Sunhapas Soodvilai
Liver X receptors (LXRs) are members of a nuclear receptor family consisting of two isoforms, LXR-α and LXR-β. They play a major role in energy metabolism including lipid and glucose metabolism. Recent studies reported LXRs regulate plasma glucose although the mechanism is still uncertain. The present study investigated whether LXR activation regulates sodium glucose cotransporter2 (SGLT2) in human renal proximal tubular cells. LXR agonists, T0901317 and GW3965, inhibited SGLT2-mediated glucose uptake in concentration-dependent manners...
November 11, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29127362/functional-analysis-of-vdr-gene-mutation-r343h-in-a-child-with-vitamin-d-resistant-rickets-with-alopecia
#17
Min-Hua Tseng, Shih-Ming Huang, Fu-Sung Lo, Jing-Long Huang, Chih-Jen Cheng, Hwei-Jen Lee, Shih-Hua Lin
The functional study of different mutations on vitamin D receptor (VDR) gene causing hereditary vitamin D-resistant rickets (HVDRR) remains limited. This study was to determine the VDR mutation and the mechanisms of this mutation-causing phenotype in a family with HVDRR and alopecia. Phenotype was analyzed, and in vitro functional studies were performed. The proband and his affected sister exhibited typical HVDRR with alopecia, and their biochemical and radiographic abnormalities but not alopecia responded to supraphysiological doses of active vitamin D3...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29126514/structural-and-functional-evidences-for-the-interactions-between-nuclear-hormone-receptors-and-endocrine-disruptors-at-low-doses
#18
Patrick Balaguer, Vanessa Delfosse, Marina Grimaldi, William Bourguet
Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system mainly by interacting with nuclear hormone receptors (NRs). Humans are generally exposed to low doses of pollutants, and current researches aim at deciphering the mechanisms accounting for the health impact of EDCs at environmental concentrations. Our correlative analysis of structural, interaction and cell-based data has revealed a variety of, sometimes unexpected, binding modes, reflecting a wide range of EDC affinities and specificities...
September 2017: Comptes Rendus Biologies
https://www.readbyqxmd.com/read/29121869/ablation-of-epidermal-rxr%C3%AE-in-cooperation-with-activated-cdk4-and-oncogenic-nras-generates-spontaneous-and-acute-neonatal-uvb-induced-malignant-metastatic-melanomas
#19
Sharmeen Chagani, Rong Wang, Evan L Carpenter, Christiane V Löhr, Gitali Ganguli-Indra, Arup K Indra
BACKGROUND: Understanding the underlying molecular mechanisms involved in the formation of cutaneous malignant melanoma is critical for improved diagnosis and treatment. Keratinocytic nuclear receptor Retinoid X Receptor α (RXRα) has a protective role against melanomagenesis and is involved in the regulation of keratinocyte and melanocyte homeostasis subsequent acute ultraviolet (UV) irradiation. METHODS: We generated a trigenic mouse model system (RXRα (ep-/-) | Tyr-NRAS (Q61K) | CDK4 (R24C/R24C) ) harboring an epidermal knockout of Retinoid X Receptor α (RXRα (ep-/-) ), combined with oncogenic NRAS (Q61K) (constitutively active RAS) and activated CDK4 (R24C/R24C) (constitutively active CDK4)...
November 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29120899/association-of-a-3-untranslated-region-polymorphism-in-proprotein-convertase-subtilisin-kexin-type-9-with-hiv-viral-load-and-cd4-levels-in-hiv-hepatitis-c-virus-coinfected-women
#20
Mark H Kuniholm, Hua Liang, Kathryn Anastos, Deborah Gustafson, Seble Kassaye, Marek Nowicki, Beverly E Sha, Emilia J Pawlowski, Stephen J Gange, Bradley E Aouizerat, Tatiana Pushkarsky, Michael I Bukrinsky, Vinayaka R Prasad
OBJECTIVE: To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. DESIGN: Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. METHODS: We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women...
November 28, 2017: AIDS
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