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retinoid investigation

Rehan M Hussain, Ninel Z Gregori, Thomas A Ciulla, Byron L Lam
Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options. Areas covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields...
March 15, 2018: Expert Opinion on Pharmacotherapy
James Q Del Rosso, Linda Stein Gold, Sandra Marchese Johnson, Maria Jose Rueda, Hilary Baldwin, Edward L Lain, Megan Landis, Marta Rendon, Emil Tanghetti, Jonathan Weiss
INTRODUCTION: Acne treatment guidelines suggest a combination approach with topical therapy including a topical retinoid, benzoyl peroxide and an oral antibiotic, or oral isotretinoin (OI), as first-line treatment options for severe acne vulgaris (AV). This study evaluated the efficacy and safety of a daily regimen of 0.3% adapalene and 2.5% benzoyl peroxide (0.3% A/BPO) gel and oral doxycycline 100 mg twice daily in severe (nonnodulocystic, non-conglobate) inflammatory AV. METHODS: This was a phase 4, 12-week, single-arm, openlabel, multi-center investigational study...
March 1, 2018: Journal of Drugs in Dermatology: JDD
Po-Jung Pao, Eszter Emri, Safiya Bishar Abdirahman, Talha Soorma, Hui-Hui Zeng, Stefanie M Hauck, Richard B Thompson, Imre Lengyel
Population-based and interventional studies have shown that elevated zinc levels can reduce the progression to advanced age-related macular degeneration. The objective of this study was to assess whether elevated extracellular zinc has a direct effect on retinal pigment epithelial cells (RPE), by examining the phenotype and molecular characteristics of increased extracellular zinc on human primary RPE cells. Monolayers of human foetal primary RPE cells were grown on culture inserts and maintained in medium supplemented with increasing total concentrations of zinc (0, 75, 100, 125 and 150 μM) for up to 4 weeks...
March 1, 2018: Journal of Trace Elements in Medicine and Biology
Edward T Morgan, Joseph L Dempsey, Sylvie M Mimche, Tracey J Lamb, Supriya Kulkarni, Julia Yue Cui, Hyunyoung Jeong, Angela L Slitt
This article is a report on a symposium entitled "Physiological Regulation of Drug Metabolism and Transport" sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2017 meeting in Chicago, IL. The contributions of physiological and pathophysiological regulation of drug metabolizing enzymes and transporters to interindividual variability in drug metabolism are increasingly recognized, but are in many cases not well understood. The presentations herein discuss the phenomenology, consequences and mechanism of such regulation...
March 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Adam M Reitzel, Jason Macrander, Daniel Mane-Padros, Bin Fang, Frances M Sladek, Ann M Tarrant
Nuclear receptors are a superfamily of transcription factors restricted to animals. These transcription factors regulate a wide variety of genes with diverse roles in cellular homeostasis, development, and physiology. The origin and specificity of ligand binding within lineages of nuclear receptors (e.g., subfamilies) continues to be a focus of investigation geared toward understanding how the functions of these proteins were shaped over evolutionary history. Among early-diverging animal lineages, the retinoid X receptor (RXR) is first detected in the placozoan, Trichoplax adhaerens...
March 3, 2018: Journal of Steroid Biochemistry and Molecular Biology
Maria Diedrichs-Möhring, Ulrike Kaufmann, Gerhild Wildner
Autoimmune diseases usually follow a relapsing-remitting or a chronic progressive course. To understand the underlying immunopathogenesis we investigated experimental Lewis rat models displaying both disease types, which were only dependent on the autoantigen peptide used for immunization. Retinal S-Antigen-peptide PDSAg induces chronic, monophasic disease, whilst interphotoreceptor retinoid-binding protein (IRBP)-peptide R14 causes a spontaneously relapsing-remitting course. R14-mediated uveitis can be re-induced by immunization; PDSAg-induced disease is even preventable by prior CFA-injection...
February 26, 2018: Progress in Retinal and Eye Research
Jianxiang Song, Woda Shi, Wencai Wang, Yajun Zhang, Shiying Zheng
Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA) are the two most common types of esophageal cancer, which is the sixth highest cause of cancer‑associated mortality and the eighth most common cancer worldwide. Gene associated with retinoid‑interferon (IFN)‑induced mortality‑19 (Grim‑19) is reported to be a cell death activator that may be used to define mechanisms involved in IFN‑β‑ and retinoic acid‑induced cell death and apoptosis in a number of tumor cell lines...
February 27, 2018: Molecular Medicine Reports
Gargi Rai, Shukla Das, Mohammad Ahmad Ansari, Praveen Kumar Singh, Neelima Gupta, Sonal Sharma, Naseem Akhter, Vishnampettai G Ramachandran, Shafiul Haque, Sajad Ahmad Dar
Interleukin-17 producing T helper (Th17) and regulatory T cells (Treg) cells have been identified to play a critical role in atopic inflammation. However, conflicting reports on the role of Th17/Treg cells in allergic fungal rhinosinusitis (AFRS) patients of different ethnicities has mystified its pathogenesis. To better understand the pathophysiological mechanisms involved in AFRS, we conducted a prospective, analytical, case-control study involving 40 confirmed immunocompetent AFRS patients and 20 healthy controls...
February 20, 2018: International Immunopharmacology
Maria Diedrichs-Möhring, Sandy Niesik, Claudia S Priglinger, Stephan R Thurau, Franz Obermayr, Stefan Sperl, Gerhild Wildner
BACKGROUND: Uveitis is a potentially blinding inflammatory disease of the inner eye with a high unmet need for new therapeutic interventions. Here, we wanted to investigate the suppressive effect of the intraocular application of the small molecule dihydroorotate dehydrogenase (DHODH)-inhibitor PP-001 on experimental relapsing rat uveitis and furthermore determine its effect on proliferation and cytokine secretion of human peripheral blood lymphocytes (PBL) and human retinal pigment epithelial (RPE) cells in vitro...
February 21, 2018: Journal of Neuroinflammation
Parvin Mansouri, Zahra Azizian, Zeinab Najafi, Somaye Hejazi, Shima Younespour
BACKGROUND: Oral Isotretinoin (13-cis-retinoic acid)is a gold standardtreatment for severe forms of acne with cheilitis as a most frequent complication.we designed this novel study to investigate the therapeutic effect of Trichloroacetic Acid(TCA) 33% as compared with placebo to treat cheilitis. METHODS: In this pilot study, 90 acne vulgaris patients between 18 to 50 years, who refered dermatologic clinic with cheilitis, were assigned to either case (TCA) or control (Vaseline) group using permuted-block randomization from 2013 to 2015,with data analysis in 2016...
February 21, 2018: Journal of Dermatological Treatment
Abu Sadat Md Sayem, Nelli Giribabu, Kamarulzaman Karim, Lay Khiang Si, Sekaran Muniandy, Naguib Salleh
Sex-steroids play important role in modulating uterine functions. We hypothesized that these hormones affect expression of proteins in the uterus related to thyroid hormone action. Therefore, changes in expression levels of receptors for thyroid hormone (TRα-1 and TRβ-1), thyroid stimulating hormone (TSHR), vitamin D (VDR) and retinoid acid (RAR) as well as extracellular signal-regulated kinase (ERK1/2) in uterus were investigated under sex-steroid influence. METHODS: Two rat models were used: (i) ovariectomised, sex-steroid replaced and (ii) intact, at different phases of oestrous cycle...
February 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zheng-Wei Fu, Zhen-Yu Zhang, Hai-Yan Ge
Efficient delivery routes are critical for the effectiveness of adipose-derived mesenchymal stem cells (ADMSCs) in treating inflammatory bowel disease (IBD). Conventional ADMSC delivery routes include local, intravenous and intraperitoneal injection. Whether mesenteric injection has potential in IBD treatment remains unknown. In the present study, we investigated the therapeutic effects of mesenteric injection of ADMSCs in a trinitrobenzene sulfonic acid-induced rat IBD model and explored whether this treatment affected T helper 17 (Th17)/regulatory T (Treg) cell ratio...
2018: American Journal of Translational Research
Rana Abdel-Samad, Patrick Aouad, Hala Gali-Muhtasib, Zeinab Sweidan, Raed Hmadi, Humam Kadara, Egildo Luca D'Andrea, Alessandra Fucci, Claudio Pisano, Nadine Darwiche
Despite advances in therapeutic strategies, colorectal cancer (CRC) remains the third cause of cancer-related deaths with a relatively low survival rate. Resistance to standard chemotherapy represents a major hurdle in disease management; therefore, developing new therapeutic agents demands a thorough understanding of their mechanisms of action. One of these compounds is ST1926, an adamantyl retinoid that has shown potent antitumor activities in several human cancer models. Here, we show that ST1926 selectively suppressed the proliferation of CRC cells while sparing normal counterparts, and significantly reduced tumor volume in a xenograft cancer mouse model...
2018: American Journal of Cancer Research
Valentina Pomatto, Erika Cottone, Paolo Cocci, Matteo Mozzicafreddo, Gilberto Mosconi, Erik Russel Nelson, Francesco Alessandro Palermo, Patrizia Bovolin
Recent studies suggest that exposure to some plasticizers, such as Bisphenol A (BPA), play a role in endocrine/metabolic dispruption and can affect lipid accumulation in adipocytes. Here, we investigated the adipogenic activity and nuclear receptor interactions of four plasticizers approved for the manufacturing of food-contact materials (FCMs) and currently considered safer alternatives. Differentiating 3T3-L1 mouse preadipocytes were exposed to scalar concentrations (0.01-25 μM) of DiNP (Di-iso-nonyl-phthalate), DiDP (Di-iso-decyl-phthalate), DEGDB (Diethylene glycol dibenzoate), or TMCP (Tri-m-cresyl phosphate)...
February 2, 2018: Journal of Steroid Biochemistry and Molecular Biology
Shinya Satoh, Kyoko Mori, Daichi Onomura, Youki Ueda, Hiromichi Dansako, Masao Honda, Shuichi Kaneko, Masanori Ikeda, Nobuyuki Kato
Ribavirin (RBV) has been widely used as an antiviral reagent, specifically for patients with chronic hepatitis C. We previously demonstrated that adenosine kinase, which monophosphorylates RBV into the metabolically active form, is a key determinant for RBV sensitivity against hepatitis C virus RNA replication. However, the precise mechanism of RBV action and whether RBV affects cellular metabolism remain unclear. Analysis of liver gene expression profiles obtained from patients with advanced chronic hepatitis C treated with the combination of pegylated interferon and RBV showed that the adenosine kinase expression level tends to be lower in patients who are overweight and significantly decreases with progression to advanced fibrosis stages...
August 2017: Hepatology Communications
Gary Loughran, Irwin Jungreis, Ioanna Tzani, Michael Power, Ruslan I Dmitriev, Ivaylo P Ivanov, Manolis Kellis, John F Atkins
Although stop codon readthrough is used extensively by viruses to expand their gene expression, verified instances of mammalian readthrough have only recently been uncovered by systems biology and comparative genomics approaches. Previously our analysis of conserved protein coding signatures that extend beyond annotated stop codons predicted stop codon readthrough of several mammalian genes, all of which have been validated experimentally. Four mRNAs display highly efficient stop codon readthrough, and these mRNAs have a UGA stop codon immediately followed by CUAG (UGA_CUAG) that is conserved throughout vertebrates...
January 31, 2018: Journal of Biological Chemistry
Anja Pemsel, Saskia Rumpf, Klaus Roemer, Kristina Heyne, Thomas Vogt, Joerg Reichrath
While nuclear cofactors that contribute to vitamin D receptor (VDR)-mediated gene transcription, including retinoid X receptors, nuclear co-activators and co-repressors, have been extensively investigated, little is known about cytoplasmic VDR-binding partners and the physiological relevance of their interaction. To gain new insight into this topic, we isolated whole-cell protein extracts of 1,25-dihydroxyvitamin D3 stimulated and UV-B-irradiated vs. non-irradiated HEK 293T cells transfected with a plasmid called pURB VDR C-Term TAP tag...
February 2018: Anticancer Research
Raphael Parens, H Frederik Nijhout, Alfredo Morales, Felipe Xavier Costa, Yaneer Bar-Yam
The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. While evidence for Zika being the cause of some of the cases is strong, its role as the primary cause of the large number of cases in Brazil has not been confirmed. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus's role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause...
November 27, 2017: PLoS Currents
Laura Kowalczuk, Alexandre Matet, Marianne Dor, Nasim Bararpour, Alejandra Daruich, Ali Dirani, Francine Behar-Cohen, Aurélien Thomas, Natacha Turck
Purpose: To investigate the molecular composition of subretinal fluid (SRF) in central serous chorioretinopathy (CSCR) and rhegmatogenous retinal detachment (RRD) using proteomics and metabolomics. Methods: SRF was obtained from one patient with severe nonresolving bullous CSCR requiring surgical subretinal fibrin removal, and two patients with long-standing RRD. Proteins were trypsin-digested, labeled with Tandem-Mass-Tag and fractionated according to their isoelectric point for identification and quantification by tandem mass spectrometry...
January 2018: Translational Vision Science & Technology
Maren Kasper, Doris Gabriel, Michael Möller, Dirk Bauer, Lena Wildschütz, Herve Courthion, Michael R R Böhm, Martin Busch, Karin Loser, Solon Thanos, Robert Gurny, Arnd Heiligenhaus
In the present study, therapeutic effect of topically applied everolimus (EV)-loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly (lactic acid) (mPEGhexPLA) nanocarriers on experimental autoimmune uveitis (EAU) were investigated. EAU was induced in B10.RIII mice via immunization with human interphotoreceptor retinoid-binding protein peptide 161-180 (hIRBPp161-180) in complete Freund's adjuvant. Everolimus-loaded mPEGhexPLA (EV/mPEGhexPLA) nanocarriers were prepared by using a solvent evaporation method...
January 8, 2018: Experimental Eye Research
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