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Retinoids

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https://www.readbyqxmd.com/read/29901398/computer-assisted-discovery-of-retinoid-x-receptor-modulating-natural-products-and-isofunctional-mimetics
#1
Daniel Merk, Francesca Grisoni, Lukas Friedrich, Elena Gelzinyte, Gisbert Schneider
Natural products (NPs) are progressively recognized as invaluable source of pharmacological tools and lead structures. To enable NP-inspired retinoid X receptor (RXR) modulator design, three novel RXR-targeting NPs were computationally identified. Among them, valerenic acid was found to be selective for RXRβ, rendering it a unique pharmacological tool compound. The NPs then served as templates for automated, ligand-based de novo design of innovative, easily accessible mimetics that inherited the biological activities of their natural templates...
June 14, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29899748/transcription-factor-retinoid-related-orphan-receptor-%C3%AE-t-a-promising-target-for-the-treatment-of-psoriasis
#2
REVIEW
Lipeng Tang, Xiaozhi Yang, Yongxin Liang, Hesong Xie, Zhenhua Dai, Guangjuan Zheng
Psoriasis, which is a common chronic inflammatory skin disease, endangers human health and brings about a major economic burden worldwide. To date, treatments for psoriasis remain unsatisfied because of their clinical limitations and various side effects. Thus, developing a safer and more effective therapy for psoriasis is compelling. Previous studies have explicitly shown that psoriasis is an autoimmune disease that is predominantly mediated by T helper 17 (Th17) cells, which express high levels of interleukin-17 (IL-17) in response to interleukin-23 (IL-23)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29894862/phytochemicals-inhibit-the-immunosuppressive-functions-of-myeloid-derived-suppressor-cells-mdsc-impact-on-cancer-and-age-related-chronic-inflammatory-disorders
#3
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth...
June 8, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29892071/%C3%AE-apo-10-carotenoids-support-normal-embryonic-development-during-vitamin-a-deficiency
#4
Elizabeth Spiegler, Youn-Kyung Kim, Beatrice Hoyos, Sureshbabu Narayanasamy, Hongfeng Jiang, Nicole Savio, Robert W Curley, Earl H Harrison, Ulrich Hammerling, Loredana Quadro
Vitamin A deficiency is still a public health concern affecting millions of pregnant women and children. Retinoic acid, the active form of vitamin A, is critical for proper mammalian embryonic development. Embryos can generate retinoic acid from maternal circulating β-carotene upon oxidation of retinaldehyde produced via the symmetric cleavage enzyme β-carotene 15,15'-oxygenase (BCO1). Another cleavage enzyme, β-carotene 9',10'-oxygenase (BCO2), asymmetrically cleaves β-carotene in adult tissues to prevent its mitochondrial toxicity, generating β-apo-10'-carotenal, which can be converted to retinoids (vitamin A and its metabolites) by BCO1...
June 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29891714/a-noncanonical-ppar%C3%AE-rxr%C3%AE-binding-sequence-regulates-leptin-expression-in-response-to-changes-in-adipose-tissue-mass
#5
Yinxin Zhang, Olof Stefan Dallner, Tomoyoshi Nakadai, Gulya Fayzikhodjaeva, Yi-Hsueh Lu, Mitchell A Lazar, Robert G Roeder, Jeffrey M Friedman
Leptin expression decreases after fat loss and is increased when obesity develops, and its proper quantitative regulation is essential for the homeostatic control of fat mass. We previously reported that a distant leptin enhancer 1 (LE1), 16 kb upstream from the transcription start site (TSS), confers fat-specific expression in a bacterial artificial chromosome transgenic (BACTG) reporter mouse. However, this and the other elements that we identified do not account for the quantitative changes in leptin expression that accompany alterations of adipose mass...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29890221/misfolded-rhodopsin-mutants-display-variable-aggregation-properties
#6
Megan Gragg, Paul S-H Park
The largest class of rhodopsin mutations causing autosomal dominant retinitis pigmentosa (adRP) is mutations that lead to misfolding and aggregation of the receptor. The misfolding mutants have been characterized biochemically, and categorized as either partial or complete misfolding mutants. This classification is incomplete and does not provide sufficient information to fully understand the disease pathogenesis and evaluate therapeutic strategies. A Förster resonance energy transfer (FRET) method was utilized to directly assess the aggregation properties of misfolding rhodopsin mutants within the cell...
June 8, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29889596/retinoic-acid-receptor-agonist-as-monotherapy-for-early-stage-mycosis-fungoides-does-it-work
#7
Iris Amitay-Laish, Ofer Reiter, Hadas Prag-Naveh, Ruben Kershenovich, Emmilia Hodak
BACKGROUND: Retinoids exert their biologic effects by binding to intracellular retinoic-acid receptors (RARs) and/or retinoid X receptors (RXRs). Early-stage mycosis fungoides (MF) has been effectively treated with bexarotene, an RXR-agonist, with overall response (OR) rates 54%-67% and complete response (CR) rates 7%-27%. Data on RAR-agonist monotherapy are limited. OBJECTIVE: To analyze the effectiveness of RAR-agonist monotherapy for early-stage MF. METHODS: Data on patients with early-stage MF treated with acitretin/isotretinoin monotherapy at a tertiary cutaneous lymphoma clinic in 2010-2017 were collected retrospectively from the medical files...
June 11, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29889063/down-regulation-of-rora-gene-expression-in-the-blood-of-multiple-sclerosis-patients
#8
Arezou Sayad, Tayyebali Salmani, Maryam Kazemzadeh Hemmesi, Maziar Ganji, Soudeh Ghafouri-Fard, Mahsa Hatami, Mohammad Soudyab, Mohammad Taheri
Multiple sclerosis (MS) is an autoimmune disease characterized by recurrent episodes of demyelination and loss of oligodendrocytes. The demyelination process is caused by various subsets of CD4+ T cells with a Th1 and Th17 phenotype. The retinoid acid-related orphan receptor A (RORA) is expressed in Th17 cells and promote Th17 differentiation. In this study, we compared the expression level of RORA gene in the blood of 50 relapsing-remitting MS (RRMS) patients who were treated with IFN-β and 50 healthy controls by TaqMan Quantitative Real-Time PCR...
May 25, 2018: Human Antibodies
https://www.readbyqxmd.com/read/29887522/relaxin-family-member-insulin-like-peptide-6-ameliorates-cardiac-fibrosis-and-prevents-cardiac-remodeling-in-murine-heart-failure-models
#9
Sonomi Maruyama, Chia-Ling Wu, Sumiko Yoshida, Dongying Zhang, Pei-Hsuan Li, Fangzhou Wu, Jennifer Parker Duffen, Rouan Yao, Blake Jardin, Ibrahim M Adham, Ronald Law, Joel Berger, Richard Di Marchi, Kenneth Walsh
BACKGROUND: The insulin/insulin-like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin-2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin-like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss-of-function and protein delivery methods. METHODS AND RESULTS: Insl6-deficient and wild-type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively, for 2 weeks...
June 10, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29884764/retinoid-x-receptor-selective-signaling-in-the-regulation-of-akt-protein-kinase-b-isoform-specific-expression
#10
Hamood AlSudais, Kawther Aabed, William Nicola, Katherine Dixon, Jihong Chen, Qiao Li
No abstract text is available yet for this article.
June 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29883603/stabbed-while-sleeping-synthetic-retinoid-antibiotics-kill-bacterial-persister-cells
#11
Maarten Fauvart, Bram Van den Bergh, Jan Michiels
Antibiotic-tolerant persister cells are difficult to eradicate by conventional classes of antibiotics. Kim and colleagues have discovered a new class of synthetic retinoid antibiotics that kill Staphylococcus aureus persisters by disrupting their cytoplasmic membrane.
June 7, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29882710/protective-role-of-carotenoids-in-the-visual-cycle
#12
Made Airanthi K Widjaja-Adhi, Srinivasagan Ramkumar, Johannes von Lintig
Exposure to light and accumulation of aberrant visual cycle by-products causes stress in the retina. The physical and chemical properties of carotenoids may provide protection against such scenario. These pigments exist in retinas of many vertebrates, including humans. However, the absence of carotenoids in mice, the preferred ophthalmologic animal model, hindered molecular and biochemical examination of the pigments' role in vision. We established a mouse model that accumulates significant amounts of carotenoids in the retina due to inactivating mutations in the Isx and Bco2 genes...
June 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29880835/uncovering-cellular-retinoic-acid-binding-protein-2-as-a-potential-target-for-rheumatoid-arthritis-synovial-hyperplasia
#13
Nerea Mosquera, Angela Rodriguez-Trillo, Antonio Mera-Varela, Antonio Gonzalez, Carmen Conde
Rheumatoid arthritis (RA) is a systemic autoimmune disease including synovitis and synovial hyperplasia that contribute to joint destruction. Pivotal pathogenic mechanisms in this process are the dysregulated proliferation and apoptosis of fibroblast-like synoviocytes (FLS). Unfortunately, the mechanisms of FLS dysregulation are not completely elucidated. Here, we explored a new hypothesis based in the potent anti-proliferative and pro-apoptotic activity of retinoids in some types of cancer. Specifically, we investigated the role of retinoids and of the retinoic acid binding proteins, CRABP2 and FABP5, on the proliferation and apoptosis of FLS from RA by adding all-trans retinoic acid (ATRA) or silencing CRABP2 and FABP5...
June 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29879262/topical-vehicle-formulations-in-the-treatment-of-acne
#14
Lauren K Hoffman, Neal Bhatia, Joshua Zeichner, Leon H Kircik
Topical treatment is the mainstay of acne therapy. The most commonly prescribed topical medications for acne include benzoyl peroxide, clindamycin, and retinoids. Despite their effectiveness in treating mild to moderate acne vulgaris, these topical medications are found to be irritating, and are historically associated with poor tolerability and diminished patient adherence. Thus, choosing the right formulation that will be effective and well tolerated is essential. Novel formulations that optimize drug concentration and utilize improved delivery vehicles have helped to enhance the tolerability and efficacy, and allow for less frequent application or co-application of drugs that were previously considered incompatible...
June 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29879250/frequency-of-treatment-switching-for-spironolactone-compared-to-oral-tetracycline-class-antibiotics-for-women-with-acne-a-retrospective-cohort-study-2010-2016
#15
John S Barbieri, Juliana K Choi, Nandita Mitra, David J Margolis
BACKGROUND: Long-term oral antibiotic use in acne may be associated with a variety of adverse effects including antibiotic resistance, pharyngitis, inflammatory bowel disease, and breast and colon cancer. Spironolactone may represent an effective and safe alternative to oral antibiotics for women with moderate to severe acne, however comparative studies are lacking. METHODS: Using the OptumInsight™ Clinformatics™ DataMart, we conducted a retrospective analysis of the frequency of switching to a different systemic agent within the first year of therapy among women with acne who were started on either spironolactone or an oral tetracycline-class antibiotic between 2010-2016, after controlling for age, topical retinoid, and oral contraceptive use...
June 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29871924/a-non-retinoid-antagonist-of-retinol-binding-protein-4-rescues-phenotype-in-a-model-of-stargardt-disease-without-inhibiting-the-visual-cycle
#16
Boglarka Racz, Andras Varadi, Jian Kong, Rando Allikmets, Paul G Pearson, Graham Johnson, Christopher L Cioffi, Konstantin Petrukhin
A primary pathological defect in the heritable eye disorder Stargardt disease is excessive accumulation of cytotoxic lipofuscin bisretinoids in the retina. Age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) matches the age-dependent increase in the incidence of the atrophic (dry) form of age-related macular degeneration (AMD) and therefore may be one of several pathogenic factors contributing to AMD progression. Lipofuscin bisretinoid synthesis in the retina depends on the influx of serum retinol from the circulation into the RPE...
June 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29870716/integrating-into-the-rhombomere-community-across-the-border
#17
Taro Kitazawa, Filippo M Rijli
During early hindbrain development, single neuroepithelial progenitors cross into neighboring rhombomere compartments and switch their molecular identity to match their new position. In this issue of Developmental Cell,Addison et al. (2018) show that this identity switch is mediated by non-cell-autonomous retinoid signaling that ensures a homogeneous segment identity.
June 4, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29864665/environmentally-relevant-concentrations-of-di-2-ethylhexyl-phthalate-exposure-alter-larval-growth-and-locomotion-in-medaka-fish-via-multiple-pathways
#18
Wen-Kai Yang, Li-Fen Chiang, Shi-Wei Tan, Pei-Jen Chen
Di(2-ethylhexyl)phthalate (DEHP) is a commonly used plasticizer, with evidence of ubiquitous human exposure and widespread occurrence in the aquatic environment. It is an emerging environmental pollutant with regulatory priority; however, most studies have focused on the toxicity of DEHP related to endocrine disruption and reproduction in mammals. The ecotoxicological impact of phthalates (e.g., DEHP) on early life stages of fish under environmentally relevant concentrations of chronic exposure remains unclear...
June 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29862999/retinoid-receptor-related-orphan-receptor-alpha-a-key-gene-setting-brain-circuits
#19
Tania Vitalis, Jean Mariani
The retinoid receptor-related orphan receptor alpha (RORα) is thought to act as a constitutive activator of transcription by binding to the ROR response element (RORE) of target genes. Several mouse models in which RORα is defective have revealed the decisive roles of RORα on the development, maturation and neuroprotection of various cerebral regions including the cerebellar and somatosensory systems. We have recently shown that RORα is needed for accurate thalamic sensory system organization and somatosensory cortex development...
May 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29860300/retinoid-x-receptor-activation-during-adipogenesis-of-female-mesenchymal-stem-cells-programs-a-dysfunctional-adipocyte
#20
Bassem M Shoucri, Victor T Hung, Raquel Chamorro-García, Toshi Shioda, Bruce Blumberg
Early life exposure to endocrine disrupting chemicals (EDCs) is an emerging risk factor for the development of obesity and diabetes later in life. We previously showed that prenatal exposure to the EDC tributyltin (TBT) results in increased adiposity in the offspring. These effects linger into adulthood and are propagated through successive generations. TBT activates two nuclear receptors, the peroxisome proliferator-activated receptor γ (PPARγ) and its heterodimeric partner retinoid X receptor (RXR), that promote adipogenesis in vivo and in vitro...
May 31, 2018: Endocrinology
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