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    Malaria, Epstein-Barr virus infection, and the Pathogenesis of Burkitt's Lymphoma.
    Int J Cancer 2017 Jul 13. Epub 2017 Jul 13.
    Chief, Division of Hematology-Oncology, Department of Pediatrics, University of Mississippi Medical Center, 1600 North State Street, Jackson, MS, 39216.
    A geographical and causal connection has long been recognized between malaria, Epstein-Barr virus (EBV) infection and Burkitt's lymphoma (BL), but the underlying mechanisms remain obscure. Potential clues are that the malaria parasite Plasmodium falciparum selectively absorbs vitamin A from the host and depends on it for its biological activities; secondly, alterations in vitamin A (retinoid) metabolism have been implicated in many forms of cancer, including BL. The first author has proposed that the merozoite-stage malaria parasite, emerging from the liver, uses its absorbed vitamin A as a cell membrane destabilizer to invade the red blood cells, causing anemia and other signs and symptoms of the disease as manifestations of an endogenous form of hypervitaminosis A (Mawson AR. Read More

    Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance.
    Proc Nutr Soc 2017 Jun 27:1-6. Epub 2017 Jun 27.
    University of Aberdeen,Institute of Medical Sciences,School of Medicine,Medical Sciences and Nutrition,Foresterhill Health Campus,Aberdeen,Scotland AB25 2ZD,UK.
    Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. Read More

    Retinoic acid pre-treatment down regulates V. cholerae outer membrane vesicles induced acute inflammation and enhances mucosal immunity.
    Vaccine 2017 Jun 22;35(28):3534-3547. Epub 2017 May 22.
    Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India. Electronic address:
    Bacterial outer membrane vesicles have been extensively investigated and considered as a next generation vaccine. Recently, we have demonstrated that the cholera pentavalent outer membrane vesicles (CPMVs) immunogen induced adaptive immunity and had a strong protective efficacy against the circulating V. cholerae strains in a mouse model. Read More

    Inhibition of gap junction intercellular communication is involved in silica nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial pathway.
    Int J Nanomedicine 2017 20;12:2179-2188. Epub 2017 Mar 20.
    Department of Toxicology, Shandong Academy of Occupational Health and Occupational Medicine, Shandong Academy of Medical Sciences.
    Gap junction intercellular communication (GJIC) between cardiomyocytes is essential for synchronous heart contraction and relies on connexin-containing channels. Connexin 43 (Cx43) is a major component involved in GJIC in heart tissue, and its abnormal expression is closely associated with various cardiac diseases. Silica nanoparticles (SNPs) are known to induce cardiovascular toxicity. Read More

    Serum Folate, Vitamin B-12, Vitamin A, γ-Tocopherol, α-Tocopherol, and Carotenoids Do Not Modify Associations between Cadmium Exposure and Leukocyte Telomere Length in the General US Adult Population.
    J Nutr 2017 Apr 8;147(4):538-548. Epub 2017 Mar 8.
    Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC.
    Background: Leukocyte telomere length (LTL) is a biomarker of the aging process and is associated with the risk of chronic disease. Higher exposure to cadmium may be associated with shorter LTL, and adequate nutrient concentrations may be associated with longer LTL; however, the potential interaction between metals and nutrients on LTL has yet to be examined.Objectives: The objective of this study was to evaluate whether serum concentrations of vitamins and carotenoids were associated with LTL, and whether they modified the association between blood cadmium and LTL in the US NHANES (1999-2002). Read More

    Inorganic mercury prevents the differentiation of SH-SY5Y cells: Amyloid precursor protein, microtubule associated proteins and ROS as potential targets.
    J Trace Elem Med Biol 2017 May 6;41:119-128. Epub 2017 Feb 6.
    Departmento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, 07360, Mexico. Electronic address:
    Exposure to mercury (Hg) occurs through different pathways and forms including methylmecury (MeHg) from seafood and rice, ethylmercury (EtHg), and elemental Hg (Hg(0)) from dental amalgams and artisanal gold mining. Once in the brain all these forms are transformed to inorganic Hg (I-Hg), where it bioaccumulates and remains for long periods. Hg is a well-known neurotoxicant, with its most damaging effects reported during brain development, when cellular key events, such as cell differentiation take place. Read More

    Carotenoid glycosides from cyanobacteria are teratogenic in the zebrafish (Danio rerio) embryo model.
    Chemosphere 2017 May 31;174:478-489. Epub 2017 Jan 31.
    Department of Chemistry and Biochemistry, Marine Science Program, Florida International University, 3000 NE 151st Street, North Miami, FL 33181, USA. Electronic address:
    Toxigenicity of cyanobacteria is widely associated with production of several well-described toxins that pose recognized threats to human and ecosystem health as part of both freshwater eutrophication, and episodic blooms in freshwater and coastal habitats. However, a preponderance of evidence indicates contribution of additional bioactive, and potentially toxic, metabolites. In the present study, the zebrafish (Danio rerio) embryo was used as a model of vertebrate development to identify, and subsequently isolate and characterize, teratogenic metabolites from two representative strains of C. Read More

    Hepatic Detoxification of Bisphenol A is Retinoid-Dependent.
    Toxicol Sci 2017 05;157(1):141-155
    Department of Medicine, Columbia University, New York, NY, USA.
    Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl) propane) is a widely used industrial chemical. The extensive distribution of BPA in the environment poses risks to humans. However, the molecular mechanisms underlying BPA toxicity as well as its effective detoxification and elimination are not well understood. Read More

    [Very Severe Differentiation Syndrome in Low Risk Acute Promyelocytic Leukemia - A Peril of Differentiating Therapy].
    Dtsch Med Wochenschr 2017 Jan 23;142(2):111-114. Epub 2017 Jan 23.
    Universitätsmedizin Mannheim, III. Medizinische Klinik, Hämatologie und internistische Onkologie, Mannheim.
    History, examinations and diagnosis A young patient consulted the hospital because of spontaneous hematomas. The combination of pancytopenia and coagulopathy in the blood and the proving cytogenetic and moleculargenetic examinations of the bone marrow lead to the diagnosis of low-risk acute promyelocytic leukemia (APL). Therapy and clinical course During the combination therapy with ATRA and ATO, the patient developed a severe differentiation syndrome and hyperleukocytosis. Read More

    Congenital insensitivity to pain with anhidrosis in Sudanese children.
    Sudan J Paediatr 2016 ;16(2):80-85
    Sea Ports Corporation Hospital and Red Sea University , Port Sudan , Sudan.
    Congenital insensitivity to pain with anhidrosis (CIPA), also called hereditary sensory and autonomic neuropathy type IV (HSAN-IV), is an extremely rare autosomal recessive disease. It is characterized by insensitivity to pain, inability to sweat, episodes of hyperpyrexia, and intellectual disability. These factors render the affected persons to repeatedly injure and traumatise themselves to the degree that they become disabled. Read More

    Retinoic Acid Protects and Rescues the Development of Zebrafish Embryonic Retinal Photoreceptor Cells from Exposure to Paclobutrazol.
    Int J Mol Sci 2017 Jan 11;18(1). Epub 2017 Jan 11.
    Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung City 80424, Taiwan.
    Paclobutrazol (PBZ) is a widely used fungicide that shows toxicity to aquatic embryos, probably through rain-wash. Here, we specifically focus on its toxic effect on eye development in zebrafish, as well as the role of retinoic acid (RA), a metabolite of vitamin A that controls proliferation and differentiation of retinal photoreceptor cells, in this toxicity. Embryos were exposed to PBZ with or without RA from 2 to 72 h post-fertilization (hpf), and PBZ-treated embryos (2-72 hpf) were exposed to RA for additional hours until 120 hpf. Read More

    Role of vitamin A metabolism in IIH: Results from the idiopathic intracranial hypertension treatment trial.
    J Neurol Sci 2017 Jan 10;372:78-84. Epub 2016 Nov 10.
    Neurology, University of Iowa School of Medicine, Iowa City, IA, United States.
    Introduction: Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF. Read More

    Different doses of dexmedetomidine reduce plasma cytokine production, brain oxidative injury, PARP and caspase expression levels but increase liver oxidative toxicity in cerebral ischemia-induced rats.
    Brain Res Bull 2017 Apr 19;130:1-9. Epub 2016 Dec 19.
    Unit of Anesthesiology and Reanimation, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey.
    Cerebral ischemia-induced progression of brain, liver, and erythrocyte oxidative injuries might be modulated by dexmedetomidine (DEX) as a potent antioxidant and anti-inflammatory drug. The present study was conducted to explore whether two different doses of DEX protect against plasma cytokine and brain, liver and erythrocyte oxidative toxicity and apoptosis in cerebral ischemia-induced rats. Forty-two rats were equally divided into 7 groups. Read More

    Retinoid-like compounds produced by phytoplankton affect embryonic development of Xenopus laevis.
    Ecotoxicol Environ Saf 2017 Apr 22;138:32-38. Epub 2016 Dec 22.
    RECETOX - Research Centre for Toxic Compounds in the Environment, Masaryk University, Faculty of Science, Brno, Czech Republic.
    Teratogenic effects, which were remarkably similar to those induced by retinoic acids, have been seen in wild frogs indicating possible source of retinoids in the environment. Recent studies indicate that some cyanobacterial species can contain teratogenic retinoic acids (RAs) and their analogues. Retinoids are known to regulate important processes such as differentiation, development, and embryogenesis. Read More

    Effectiveness and safety of nutritional supplements in the treatment of hereditary retinal dystrophies: a systematic review.
    Eye (Lond) 2017 Feb 9;31(2):273-285. Epub 2016 Dec 9.
    Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Madrid, Spain.
    The hereditary retinal dystrophies (HRDs) are a group of genetically determined disorders that result in loss of the visual function. There is a lack of standard pharmacological treatments or widely accepted nutritional recommendations. The objective of this review is to summarise the scientific evidence on the effectiveness and safety of nutritional supplements for the treatment of HRDs. Read More

    Inhibition of IKKβ by celastrol and its analogues - an in silico and in vitro approach.
    Pharm Biol 2017 Dec;55(1):368-373
    a Department of Biochemistry , VRR Institute of Biomedical Science (Affiliated to University of Madras) , Chennai , Tamilnadu , India.
    Context: Alzheimer's disease (AD) is the most common form of dementia affecting the aged population and neuroinflammation is one of the most observed AD pathologies. NF-κB is the central regulator of inflammation and inhibitor κB kinase (IKK) is the converging point in NF-κB activation. Celastrol is a natural triterpene used as a treatment for inflammatory conditions. Read More

    Vitamin A and Vision.
    Subcell Biochem 2016 ;81:231-259
    Departments of Ophthalmology and Biochemistry, School of Medicine, University of Washington, 98195, Seattle, WA, USA.
    Visual systems detect light by monitoring the effect of photoisomerization of a chromophore on the release of a neurotransmitter from sensory neurons, known as rod and cone photoreceptor cells in vertebrate retina. In all known visual systems, the chromophore is 11-cis-retinal complexed with a protein, called opsin, and photoisomerization produces all-trans-retinal. In mammals, regeneration of 11-cis-retinal following photoisomerization occurs by a thermally driven isomerization reaction. Read More

    Mixtures of herbicides and metals affect the redox system of honey bees.
    Chemosphere 2017 Feb 22;168:163-170. Epub 2016 Oct 22.
    Département des Sciences Biologiques, Centre TOXEN, Université du Québec à Montréal, Montréal, Québec, Canada.
    The increasing loss of bee colonies in many countries has prompted a surge of studies on the factors affecting bee health. In North America, main crops such as maize and soybean are cultivated with extensive use of pesticides that may affect non-target organisms such as bees. Also, biosolids, used as a soil amendment, represent additional sources of metals in agroecosystems; however, there is no information about how these metals could affect the bees. Read More

    All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts.
    Int J Mol Med 2016 Dec 19;38(6):1693-1702. Epub 2016 Oct 19.
    Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, Sichuan 400016, P.R. China.
    Rosiglitazone (RSG) is a potent drug used in the treatment of insulin resistance; however, it is associated with marked skeletal toxicity. RSG-induced osteoporosis may contribute to the promotion of adipogenic differentiation at the expense of osteogenic differentiation in bone marrow stromal cells. The aim of this study was to investigate whether RSG-induced bone toxicity can be reversed by combined treatment with all-trans retinoic acid (ATRA). Read More

    Are topical retinoids teratogenic?
    G Ital Dermatol Venereol 2016 Dec 6;151(6):700-705. Epub 2016 Sep 6.
    Department of Pathophysiology and Transplantation, Università degli Studi di Milano, I.R.C.C.S. Foundation, Cà Granda Ospedale Maggiore Policlinico, Milan, Italy -
    Retinoic acid is a physiological compound of human blood. Blood levels range from 1000 to 7000 pg/mL (usually 1500-5000 pg/mL). Results of studies on absorption of topical retinoic acid in laboratory animals, although rather conflicting, demonstrate that it induces plasma concentrations which are well below concentrations caused by non-teratogenic oral doses. Read More

    Protective and therapeutic effects of fucoxanthin against sunburn caused by UV irradiation.
    J Pharmacol Sci 2016 Sep 12;132(1):55-64. Epub 2016 Aug 12.
    Molecular Toxicology Lab., Ritsumeikan University, Shiga, Japan. Electronic address:
    Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. Read More

    Comparison between the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 short-term toxicity in adult albino rats.
    Turk J Med Sci 2016 Feb 17;46(2):524-38. Epub 2016 Feb 17.
    Department of Microbiology, College of Medicine, Taif University, Taif, Saudi Arabia.
    Background/aim: Vitamin D3 has increased risk of toxicity due to its common use in multivitamin preparations. Vitamin K and vitamin A play an important role in vitamin D action. The goal of the current study was to compare the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 toxicity in rats by assessing serum calcium, renal function tests, cardiac enzymes, and related histopathological changes. Read More

    Nuclear retinoid receptors and pregnancy: placental transfer, functions, and pharmacological aspects.
    Cell Mol Life Sci 2016 Oct 9;73(20):3823-37. Epub 2016 Aug 9.
    EA7281, Retinoids, Reproduction Developmental Diseases, School of Medicine, Clermont Université, Université d'Auvergne, 63000, Clermont-Ferrand, France.
    Animal models of vitamin A (retinol) deficiency have highlighted its crucial role in reproduction and placentation, whereas an excess of retinoids (structurally or functionally related entities) can cause toxic and teratogenic effects in the embryo and foetus, especially in the first trimester of human pregnancy. Knock-out experimental strategies-targeting retinoid nuclear receptors RARs and RXRs have confirmed that the effects of vitamin A are mediated by retinoic acid (especially all-trans retinoic acid) and that this vitamin is essential for the developmental process. All these data show that the vitamin A pathway and metabolism are as important for the well-being of the foetus, as they are for that of the adult. Read More

    Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series.
    Food Chem Toxicol 2016 Jul 8. Epub 2016 Jul 8.
    Department of Complementary and Alternative Medicine, John A. Burns School of Medicine, 651 Ilalo Street, MEB 223, University of Hawaii at Manoa, Honolulu, HI, 96813, USA. Electronic address:
    Background: No online current list of potentially life-threatening, hepatotoxic herbs and dietary supplements based on PubMed case reports exists in a summarized tabular form.

    Methods: Documented case reports of herbs or dietary supplements (DS; includes herbs) appearing to contribute to liver injury were used to create an online "DS Toxic Table" of potentially hepatotoxic herbs and dietary supplements (PubMed, 1966 to June, 2016, and cross-referencing). The spectrum of DS induced liver injuries (DSILI) included elevated liver enzymes, hepatitis, steatosis, cholestasis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, veno-occlusive disease, acute liver failure requiring a liver transplant, and death. Read More

    Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells.
    Toxicol Appl Pharmacol 2016 Sep 28;306:8-16. Epub 2016 Jun 28.
    Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. Electronic address:
    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Read More

    Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice.
    Biochem Biophys Res Commun 2016 Aug 23;477(3):322-8. Epub 2016 Jun 23.
    Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China. Electronic address:
    Administration of all-trans retinoic acid (atRA) on E12.0 (embryonic day 12.0) leads to failure of medial edge epithelium (MEE) disappearance and cleft palate. Read More

    Myeloid cell leukaemia 1 has a vital role in retinoic acid-mediated protection of Toll-like receptor 9-stimulated B cells from spontaneous and DNA damage-induced apoptosis.
    Immunology 2016 Sep 25;149(1):62-73. Epub 2016 Jul 25.
    Department of Molecular Medicine, Institute of Basic Medical Science, University of Oslo, Oslo, Norway.
    Vitamin A is an essential anti-infective agent with pleiotropic effects on cells of the immune system. The goal of the present study was to unravel the impact of the vitamin A metabolite retinoic acid (RA) on B-cell survival related both to normal B-cell homeostasis and to the detrimental effects imposed by DNA-damaging agents. By combining RA with Toll-like receptor 9 (TLR9) ligands, we show that RA prevents spontaneous, irradiation- and doxorubicin-induced apoptosis of human B cells in an RA receptor-dependent manner. Read More

    Vitamin A toxicity presenting as bone pain.
    Arch Dis Child 2017 Jun 6;102(6):556-558. Epub 2016 Jun 6.
    Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India.
    A 4-year-old boy presented with severe bone pains, refusal to walk, diffuse bony swelling of forelimbs, skin changes and abdominal pain, with symptoms evolving over 6 weeks. Blood screening tests were normal except for raised aspartate aminotransferase (AST). Radiographs revealed thickened periosteum, widening of the diaphyses of long bones and lifted periosteum in mid-shaft of ulnae and right femur. Read More

    Vitamins A and E content of commercial infant foods in the UK: A cause for concern?
    Food Chem 2016 Nov 11;210:56-62. Epub 2016 Apr 11.
    Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK. Electronic address:
    According to the European Food Safety Authority, currently, there are no reliable data or robust guidelines available in relation to the micronutrient composition of infant foods. This study evaluated the intake of vitamins A and E of infants from 'ready-to-feed' foods and formulas. Normal phase high performance liquid chromatography was employed for simultaneous quantification of retinyl acetate, retinyl palmitate, α-tocopherol and γ-tocopherol, reverse phase high performance liquid chromatography for the quantification of β-carotene, and UV spectrophotometry for the quantification of carotenoids from selected infant food samples. Read More

    Radioligand binding assay for accurate determination of nuclear retinoid X receptors: A case of triorganotin endocrine disrupting ligands.
    Toxicol Lett 2016 Jul 3;254:32-6. Epub 2016 May 3.
    Institute of Experimental Endocrinology, BMC, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic. Electronic address:
    Nuclear 9-cis retinoic acid receptors (retinoid X receptors, RXR) are promiscuous dimerization partners for a number of nuclear receptors. In the present study, we established a novel in vitro method for quantitative determination of the nuclear retinoid X receptors in rat liver. One type of high affinity and limited capacity RXR specific binding sites with the Ka value ranging from 1. Read More

    Prevention of gentamicin ototoxicity with N-acetylcysteine and vitamin A.
    J Laryngol Otol 2016 May;130(5):440-6
    Department of Otorhinolaryngology,Izmir Katip Celebi University,Ataturk Training and Research Hospital,Izmir,Turkey.
    Objective: To investigate the use of systemic N-acetylcysteine and vitamin A in the prevention of gentamicin ototoxicity in rats.

    Methods: Forty-two Wistar rats were divided into four groups according to treatment: intratympanic saline, intratympanic gentamicin, intraperitoneal vitamin A after intratympanic gentamicin, and intraperitoneal N-acetylcysteine after intratympanic gentamicin. Signal-to-noise ratio and distortion product otoacoustic emissions were evaluated in all groups. Read More

    Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.
    PLoS One 2016 14;11(4):e0153556. Epub 2016 Apr 14.
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35294, United States of America.
    UAB30 is an RXR selective agonist that has been shown to have potential cancer chemopreventive properties. Due to high efficacy and low toxicity, it is currently being evaluated in human Phase I clinical trials by the National Cancer Institute. While UAB30 shows promise as a low toxicity chemopreventive drug, the mechanism of its action is not well understood. Read More

    Can the preterm lung recover from perinatal stress?
    Mol Cell Pediatr 2016 Dec 13;3(1):15. Epub 2016 Apr 13.
    Neonatology, Department of Pediatrics, Maastricht University Medical Center, Maastricht, Netherlands.
    After birth, adequate lung function is necessary for the successful adaptation of a preterm baby. Both prenatal and postnatal insults and therapeutic interventions have an immediate effect on lung function and gas exchange but also interfere with fetal and neonatal lung development. Prenatal insults like chorioamnionitis and prenatal interventions like maternal glucocorticosteroids interact but might also determine the preterm baby's lung response to postnatal interventions ("second hit") like supplementation of oxygen and drug therapy. Read More

    Hepatotoxicity by Dietary Supplements: A Tabular Listing and Clinical Characteristics.
    Int J Mol Sci 2016 Apr 9;17(4):537. Epub 2016 Apr 9.
    Servicio de Farmacología Clíınica and Unidad de Gestión Clínica (UGC) de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), 29010 Málaga, Spain.
    Dietary supplements (DS) are extensively consumed worldwide despite unproven efficacy. The true incidence of DS-induced liver injury (DSILI) is unknown but is probably under-diagnosed due to the general belief of safety of these products. Reported cases of herbals and DS-induced liver injury are increasing worldwide. Read More

    Dietary vitamin A supplementation ameliorates the effects of poly-aromatic hydrocarbons in Atlantic salmon (Salmo salar).
    Aquat Toxicol 2016 Jun 21;175:171-83. Epub 2016 Mar 21.
    NIFES, Bergen, Norway.
    Several studies have reported on the interaction between vitamin A (VA) and aryl hydrocarbon receptor (AhR)-binding toxicants, including poly-aromatic hydrocarbons (PAHs). In aquaculture, the use of plant oils in novel aquafeeds can increase PAH levels while simultaneously lowering natural VA background levels, causing the need to supplement plant oil-based feeds with synthetic VA. To study dietary VA-PAH interactions, Atlantic salmon (initial weight 195±0. Read More

    Cultured networks of excitatory projection neurons and inhibitory interneurons for studying human cortical neurotoxicity.
    Sci Transl Med 2016 Apr;8(333):333ra48
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
    Translating neuroprotective treatments from discovery in cell and animal models to the clinic has proven challenging. To reduce the gap between basic studies of neurotoxicity and neuroprotection and clinically relevant therapies, we developed a human cortical neuron culture system from human embryonic stem cells or human inducible pluripotent stem cells that generated both excitatory and inhibitory neuronal networks resembling the composition of the human cortex. This methodology used timed administration of retinoic acid to FOXG1(+) neural precursor cells leading to differentiation of neuronal populations representative of the six cortical layers with both excitatory and inhibitory neuronal networks that were functional and homeostatically stable. Read More

    Interphotoreceptor Retinoid-Binding Protein Mitigates Cellular Oxidative Stress and Mitochondrial Dysfunction Induced by All-trans-Retinal.
    Invest Ophthalmol Vis Sci 2016 Apr;57(4):1553-62
    Purpose: Point and null mutations in interphotoreceptor retinoid-binding protein (IRBP) cause retinal dystrophy in affected patients and IRBP-deficient mice with unknown mechanism. This study investigated whether IRBP protects cells from damages induced by all-trans-retinal (atRAL), which was increased in the Irbp(-/-) retina.

    Methods: Wild-type and Irbp(-/-) mice retinal explants in buffer with or without purified IBRP were exposed to 800 lux light for different times and subjected to retinoid analysis by high-performance liquid chromatography. Read More

    Effects of dietary lead exposure on vitamin levels in great tit nestlings - An experimental manipulation.
    Environ Pollut 2016 Jun 26;213:688-97. Epub 2016 Mar 26.
    Department of Biology, University of Turku, 20014 Turku, Finland.
    Exposure to metal pollution negatively affects animal physiology, including nutrient metabolism, but in the wild an effect can seldom be attributed to a single metal. Moreover, little is known about how the metabolism of vitamins, essential micronutrients for developing juveniles, is affected by toxic metals. Therefore we experimentally investigated the effects of lead (Pb), a widespread toxic metal, on four fat-soluble vitamins A (total and retinol), D3, E (total and α-tocopherol) and K and carotenoids (lutein, zeaxanthin and unidentified) in great tit (Parus major) nestlings. Read More

    A Changing Landscape for Vitamin A Programs: Implications for Optimal Intervention Packages, Program Monitoring, and Safety.
    Food Nutr Bull 2016 Jun 22;37(2 Suppl):S75-86. Epub 2016 Mar 22.
    UNICEF, West and Central Africa Regional Office, Dakar, Senegal, Africa.
    Background: Vitamin A deficiency (VAD) remains a widespread public health problem in the developing world, despite changes in under-5 mortality rates, morbidity patterns, and intervention options.

    Objective: This article considers the implications of a changing epidemiologic and programmatic landscape for vitamin A (VA) programs.

    Methods: We review progress to prevent VAD and its health consequences, assess gaps in VA status and intervention coverage data, and assess data needed to guide decisions regarding the optimal mix, targeting, and dose of VA interventions to maximize benefit and minimize risk. Read More

    The Effects of Arsenic Trioxide in Combination with Retinoic Acids on Cutaneous T-Cell Lymphoma Cell Lines.
    Skin Pharmacol Physiol 2016 23;29(2):63-70. Epub 2016 Mar 23.
    Skin Cancer Centre Charitx00E9;, Department of Dermatology and Allergy, Charitx00E9; - Universitx00E4;tsmedizin Berlin, Berlin, Germany.
    Cutaneous T-cell lymphomas (CTCL) are characterized by an infiltration of the skin with malignant T cells. Curative treatments for aggressive entities such as Sézary syndrome have not been identified yet. Arsenic trioxide (AsO3) is used for the treatment of acute promyelocytic leukemia in combination with retinoids. Read More

    NPM and BRG1 Mediate Transcriptional Resistance to Retinoic Acid in Acute Promyelocytic Leukemia.
    Cell Rep 2016 Mar 17;14(12):2938-49. Epub 2016 Mar 17.
    Division of Experimental Medicine, Department of Oncology, Segal Cancer Centre and Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC H3T 1E2, Canada. Electronic address:
    Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We uncovered an aberrant interaction among PML/RARA, nucleophosmin (NPM), and topoisomerase II beta (TOP2B). Read More

    Influence of Serum Levels of Vitamins A, D, and E as well as Vitamin D Receptor Polymorphisms on Micronucleus Frequencies and Other Biomarkers of Genotoxicity in Workers Exposed to Formaldehyde.
    J Nutrigenet Nutrigenomics 2015 18;8(4-6):205-14. Epub 2016 Mar 18.
    Environment and Health Research Group, Escola Superior de Tecnologia da Sax00FA;de de Lisboa - IPL, Lisbon, Portugal.
    Background/aim: Formaldehyde is classified as carcinogenic to humans, making it a major concern, particularly in occupational settings. Fat-soluble vitamins, such as vitamins A, D, and E, are documented as antigenotoxic and antimutagenic and also correlate with the cell antioxidant potential. This study investigates the influence of these vitamins on genotoxicity biomarkers of formaldehyde-exposed hospital workers. Read More

    Garlic capsule and selenium-vitamins ACE combination therapy modulate key antioxidant proteins and cellular adenosine triphosphate in lisinopril-induced lung damage in rats.
    Drug Metab Pers Ther 2016 Mar;31(1):47-54
    Background: Garlic capsule (GAR) and/or selenium- vitamin A, C, E (S-VACE) might be useful in the treatment of lung diseases. The present study evaluated the toxicity of lisinopril (LIS) in the lungs of male rats and the reversal effect of GAR and/or selenium-vitamins A, C, and E (S-VACE).

    Methods: Group I served as the control, whereas animals in groups II, III, IV, and V received 28 mg of LIS/kg body weight by gavage. Read More

    All trans-retinoic acid analogs promote cancer cell apoptosis through non-genomic Crabp1 mediating ERK1/2 phosphorylation.
    Sci Rep 2016 Mar 3;6:22396. Epub 2016 Mar 3.
    Department of Pharmacology University of Minnesota, Minneapolis, MN 55455, USA.
    All trans retinoic acid (atRA) is one of the most potent therapeutic agents, but extensive toxicity caused by nuclear RA receptors (RARs) limits its clinical application in treating cancer. AtRA also exerts non-genomic activities for which the mechanism remains poorly understood. We determine that cellular retinoic acid binding protein 1 (Crabp1) mediates the non-genomic activity of atRA, and identify two compounds as the ligands of Crabp1 to rapidly and RAR-independently activate extracellular signal regulated kinase 1/2 (ERK1/2). Read More

    Development of a quantitative morphological assessment of toxicant-treated zebrafish larvae using brightfield imaging and high-content analysis.
    J Appl Toxicol 2016 09 29;36(9):1214-22. Epub 2016 Feb 29.
    National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC, USA.
    One of the rate-limiting procedures in a developmental zebrafish screen is the morphological assessment of each larva. Most researchers opt for a time-consuming, structured visual assessment by trained human observer(s). The present studies were designed to develop a more objective, accurate and rapid method for screening zebrafish for dysmorphology. Read More

    Differential Regulation of Bcl-xL Gene Expression by Corticosterone, Progesterone, and Retinoic Acid.
    J Biochem Mol Toxicol 2016 Jun 25;30(6):309-16. Epub 2016 Feb 25.
    Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, 85724, USA.
    Corticosterone (CT), progesterone (PG), and retinoic acid (RA) are capable of inhibiting Doxorubicin (Dox) from inducing apoptosis in rat cardiomyocytes. Mechanistically, CT, PG, and RA induce increases of Bcl-xL protein and mRNA, and activate a 3.2 kb bcl-x gene promoter. Read More

    Quantification of ecdysteroids and retinoic acids in whole daphnids by liquid chromatography-triple quadrupole mass spectrometry.
    J Chromatogr A 2016 Mar 4;1438:57-64. Epub 2016 Feb 4.
    Department of Chemistry, Université de Sherbrooke, Sherbrooke, QC J1 K 2R1, Canada. Electronic address:
    Quantification of ecdysteroids and retinoic acids at picograms per individual is typically achieved with radioimmunoassay methods. However, those methods cannot identify individual types of ecdysteroids or provide an absolute concentration, which poses problems for comparative assays such as the metabolic profiling approach for toxicity testing. The method described in the present paper, based on liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry, was developed to allow the quantification in whole daphnids extracts of ecdysteroids (20-hydroxyecdysone, ecdysone, ponasterone A) and retinoic acid (sum of isomers). Read More

    The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.
    Neural Plast 2016 3;2016:3707406. Epub 2016 Jan 3.
    Department of Psychiatry, University Hospital Geneva, Chêne-Bourg, 1225 Geneva, Switzerland; Geneva Neuroscience Center, Geneva University, 1211 Geneva, Switzerland.
    The amyloid-β peptide or Aβ is the key player in the amyloid-cascade hypothesis of Alzheimer's disease. Aβ appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer's disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. Read More

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