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https://www.readbyqxmd.com/read/27923259/-established-therapies-and-new-therapeutic-strategies-in-alcoholic-liver-disease
#1
Helmut Karl Seitz, Sebastian Mueller
Chronical alcohol abuse causes more than 200 diseases and/or symptoms and among these alcoholic liver disease (ALD) is of special importance since it occurs frequently and may be life-threatening. In Europe alcohol consumption as well as ALD increased as compared to the rest of the world. It has been estimated that in Europe approximately 500 000 people die every year due to ALD. ALD consists of alcoholic fatty liver, alcoholic steatohepatitis (ASH), alcoholic cirrhosis and hepatocellar cancer (HCC ). Alcohol hepatitis (AH) is a clinical feature with jaundice and liver failure and a high mortality...
December 6, 2016: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/27923152/hydronephrosis-in-the-wnt5a-ablated-kidney-is-caused-by-an-abnormal-ureter-bladder-connection
#2
Kangsun Yun, Alan O Perantoni
The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme...
December 3, 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27923110/impact-of-oligonucleotide-structure-chemistry-and-delivery-method-on-in-vitro-cytotoxicity
#3
Maja M Janas, Yongfeng Jiang, Mark K Schlegel, Scott Waldron, Satya Kuchimanchi, Scott A Barros
Single-stranded (ss) 2'-fluoro (2'-F)-modified oligonucleotides (ONs) with a full phosphorothioate (PS) backbone have been reported to be cytotoxic and cause DNA double-strand breaks (DSBs) when transfected into HeLa cells. However, the molecular determinants of these effects have not been fully explored. In this study, we investigated the impact of ON structure, chemistry, delivery method, and cell type on in vitro cytotoxicity and DSBs. We found that ss PS-ONs were more cytotoxic than double-stranded (ds) PS-ONs, irrespective of the 2'-ribose chemistry, inclusive of the 2'-F modification...
December 6, 2016: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/27923069/characterization-in-helicobacter-pylori-of-a-nickel-transporter-essential-for-colonization-that-was-acquired-during-evolution-by-gastric-helicobacter-species
#4
Frédéric Fischer, Marie Robbe-Saule, Evelyne Turlin, Francesco Mancuso, Valérie Michel, Pierre Richaud, Frédéric J Veyrier, Hilde De Reuse, Daniel Vinella
Metal acquisition is crucial for all cells and for the virulence of many bacterial pathogens. In particular, nickel is a virulence determinant for the human gastric pathogen Helicobacter pylori as it is the cofactor of two enzymes essential for in vivo colonization, urease and a [NiFe] hydrogenase. To import nickel despite its scarcity in the human body, H. pylori requires efficient uptake mechanisms that are only partially defined. Indeed, alternative ways of nickel entry were predicted to exist in addition to the well-described NixA permease...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27923035/biomarkers-in-anal-cancer-from-biological-understanding-to-stratified-treatment
#5
Christopher M Jones, Vicky Goh, David Sebag-Montefiore, Duncan C Gilbert
Squamous cell carcinomas of the anus and anal canal represent a model of a cancer and perhaps the first where level 1 evidence supported primary chemoradiotherapy (CRT) in treating locoregional disease with curative intent. The majority of tumours are associated with infection with oncogenic subtypes of human papilloma virus and this plays a significant role in their sensitivity to treatment. However, not all tumours are cured with CRT and there remain opportunities to improve outcomes in terms of oncological control and also reducing late toxicities...
December 6, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27922821/identification-of-salvia-haenkei-as-gerosuppressant-agent-by-using-an-integrated-senescence-screening-assay
#6
Ivana Matic, Ajinkya Revandkar, Jingjing Chen, Angela Bisio, Stefano Dall'Acqua, Veronica Cocetta, Paola Brun, Giorgio Mancino, Martina Milanese, Maurizio Mattei, Monica Montopoli, Andrea Alimonti
Cellular senescence is a stable cell cycle arrest that is the causative process of aging. The PI3K/AKT/mTOR pathway is implicated in the control of cellular senescence and inhibitors of this pathway have been successfully used for life span prolongation experiments in mammals. PTEN is the major regulator of the PI3K/AKT/mTOR pathway and loss of PTEN promotes a senescence response termed PICS. Here we report a novel-screening assay, for the identification of compounds that block different types of senescence response...
December 1, 2016: Aging
https://www.readbyqxmd.com/read/27922762/nonchemotherapy-drug-induced-agranulocytosis-in-children-detected-by-a-prospective-pharmacovigilance-program
#7
Nicolás Medrano-Casique, Hoi Y Tong, Alberto M Borobia, Antonio J Carcas, Jesús Frías, Elena Ramírez
OBJECTIVES: A prospective evaluation of nonchemotherapy drug-induced agranulocytosis (DIA) cases, which are infrequent in the pediatric population. We characterize agranulocytosis cases and assess lab test differences between drug- and nondrug-induced agranulocytosis. METHODS: Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital we detected pediatric agranulocytosis cases from July 2007 to December 2010. This program estimates the incidence, drug causality, clinical features, outcomes of DIA pediatric cases, and assesses laboratory differences with respect to non-DIA...
December 6, 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27922746/plant-extracts-initial-screening-identification-of-bioactive-compounds-and-effect-against-candida-albicans-biofilms
#8
Fernanda Lourenção Brighenti, Marcos José Salvador, Aline Vidal Lacerda Gontijo, Alberto Carlos Botazzo Delbem, Ádina Cléia Botazzo Delbem, Cristina Pacheco Soares, Maria Alcionéia Carvalho de Oliveira, Camila Miorelli Girondi, Cristiane Yumi Koga-Ito
AIM: This study screened plants from Brazilian Pantanal for Candida albicans antibiofilm activity. MATERIAL & METHODS: Sixty extracts were obtained from ten plants using different extraction methods. Antifungal activity was assessed. Effects on biofilm inhibition and disruption and cytotoxicity were also evaluated. The most active extract was chemically characterized. RESULTS:  Buchenavia tomentosa ethanolic extract showed noticeable antifungal activity and was selected for biofilm experiments...
December 6, 2016: Future Microbiology
https://www.readbyqxmd.com/read/27922739/tyrosine-kinase-aurora-kinase-and-leucine-aminopeptidase-as-attractive-drug-targets-in-anticancer-therapy-characterisation-of-their-inhibitors
#9
Joanna Ziemska, Jolanta Solecka
Cancers are the leading cause of deaths all over the world. Available anticancer agents used in clinics exhibit low therapeutic index and usually high toxicity. Wide spreading drug resistance of cancer cells induce a demanding need to search for new drug targets. Currently, many on-going studies on novel compounds with potent anticancer activity, high selectivity as well as new modes of action are conducted. In this work, we describe in details three enzyme groups, which are at present of extensive interest to medical researchers and pharmaceutical companies...
2016: Roczniki Państwowego Zakładu Higieny
https://www.readbyqxmd.com/read/27922672/2-methoxycinnamaldehyde-inhibits-the-tnf-%C3%AE-induced-proliferation-and-migration-of-human-aortic-smooth-muscle-cells
#10
Young-Hee Jin, Soo-A Kim
The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a crucial event in the development of atherosclerosis, and tumor necrosis factor-α (TNF-α) is actively involved in this process by enhancing the proliferation and migration of VSMCs. 2-Methoxycinnamaldehyde (MCA) is a natural compound of Cinnamomum cassia. Although 2-hydroxycinnamaldehyde (HCA), another compound from Cinnamomum cassia, has been widely studied with regard to its antitumor activity, MCA has not attracted researchers' interest due to its mild toxic effects on cancer cells and its mechanisms of action remain unknown...
December 6, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27922549/unreported-side-effect-of-intravitreal-diclofenac-in-chronic-diabetic-macular-edema
#11
Lavanya Chidambara, Rekha Singhal, Priya Srinivasan, Naresh Kumar Yadav
PURPOSE: To evaluate the safety and efficacy of intravitreal diclofenac sodium. METHODS: A 61-year-old male with persistent diabetic macular edema was treated with 450 μg of intravitreal diclofenac sodium (systemic preparation). RESULTS: Postinjection Day 1, the spectral domain optical coherence tomography showed irregular vitreoretinal interface with wrinkling and separation of the internal limiting membrane from the nerve fiber layer with homogeneity of the inner layers...
December 2, 2016: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/27922528/lung-cancer-risk-associated-with-regulated-and-unregulated-chrysotile-asbestos-fibers
#12
Ghassan B Hamra, David B Richardson, John Dement, Dana Loomis
BACKGROUND: Regulation of asbestos fibers in the workplace is partly determined by which fibers can be visually counted. However, a majority of fibers are too short and thin to count this way and are, consequently, not subject to regulation. METHODS: We estimate lung cancer risk associated with asbestos fibers of varying length and width. We apply an order-constrained prior both to leverage external information from toxicological studies of asbestos health effects...
December 1, 2016: Epidemiology
https://www.readbyqxmd.com/read/27922500/facioscapulohumeral-muscular-dystrophy
#13
Jeffrey M Statland, Rabi Tawil
PURPOSE OF REVIEW: This article describes the clinical characteristics, diagnosis, molecular pathogenesis, and treatment of facioscapulohumeral muscular dystrophy (FSHD). RECENT FINDINGS: FSHD comprises two genetically distinct types that converge on a common downstream pathway of the expression of the toxic protein DUX4. Approximately 95% of patients have FSHD type 1 (FSHD1), in which loss of DNA repetitive elements (D4Z4 repeats) in the subtelomeric region of chromosome 4q causes decreased methylation and epigenetic derepression of DUX4, a gene contained within each D4Z4 repeat...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27922495/toxic-and-endocrine-myopathies
#14
Hans D Katzberg, Charles D Kassardjian
PURPOSE OF REVIEW: This article discusses the clinical features, pathophysiology, and management of toxic and endocrine myopathies. RECENT FINDINGS: Early detection and expeditious correction of metabolic disturbances in endocrinopathies such as Cushing syndrome, thyroid and parathyroid diseases, and acromegaly can minimize and prevent neurologic complications including myopathy. Recently proposed mechanisms of injury in patients with critical illness myopathy include inhibition of protein synthesis, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, oxidative stress, and disruption of intramuscular calcium homeostasis, which can cause a myosin-loss myopathy...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27922333/environmentally-relevant-chronic-low-dose-tritium-and-gamma-exposures-do-not-increase-somatic-intrachromosomal-recombination-in-pkz1-mouse-spleen
#15
Laura Bannister, Mandy Serran, Lindsey Bertrand, Dmitry Klokov, Heather Wyatt, Melinda Blimkie, Yann Gueguen, Nicholas Priest, Jean-René Jourdain, Pamela Sykes
The toxicity of tritium is a public health concern given its presence and mobility in the environment. For risk predictions using radiological protection models, it is essential to allocate an appropriate radiation weighting factor (WR). This in turn should be consistent with the observed relative biological effectiveness (RBE) of tritium beta radiation. Although the International Commission on Radiological Protection (ICRP) currently recommends a WR of 1 for the calculation of committed effective dose for X rays, gamma rays and electrons of all energies, including tritium energies, there are concerns that tritium health risks are underestimated and that current regulatory tritium drinking water standards need revision...
December 6, 2016: Radiation Research
https://www.readbyqxmd.com/read/27922280/ganetespib-for-small-cell-lung-cancer
#16
Deepa S Subramaniam, Eiran A Warner, Giuseppe Giaccone
Heat shock proteins (Hsps) are part of a complex network of chaperone proteins that are critically involved in the conformational maturation of intracellular proteins and regulate their degradation via the proteasome system Hsps (especially Hsp70 and Hsp90) are upregulated in many cancers and are potentially attractive therapeutic targets. Ganetespib is a potent non-geldanamycin analogue, and avoids the toxicities associated with older analogues due to its small molecular weight, lipophilicity and the absence of the benzoquinone moiety; strong pre-clinical data support its evaluation in lung cancer, especially small cell lung cancer (SCLC)...
December 6, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27922184/europium-iii-and-uranium-vi-complexation-by-natural-organic-matter-nom-effect-of-source
#17
Ralf Kautenburger, Jonas M Sander, Christina Hein
For the safe long-term storage of high level radioactive waste (HLW), detailed information about geo-chemical behavior of radioactive and toxic metal ions under environmental conditions is important. Natural organic matter (NOM) can play a crucial role in the immobilization or mobilization of these metal ions due to its complexation and colloid formation tendency. In this study, the complexation of europium (as chemical homologue of trivalent actinides like americium) and uranium (as main component of HLW) by ten humic acids (HA) from different sources and Suwannee NOM river extract has been analyzed...
December 6, 2016: Electrophoresis
https://www.readbyqxmd.com/read/27922119/in-situ-particles-reorientation-during-magnetic-hyperthermia-application-shape-matters-twice
#18
Konstantinos Simeonidis, M Puerto Morales, Marzia Marciello, Makis Angelakeris, Patricia de la Presa, Ana Lazaro-Carrillo, Andrea Tabero, Angeles Villanueva, Oksana Chubykalo-Fesenko, David Serantes
Promising advances in nanomedicine such as magnetic hyperthermia rely on a precise control of the nanoparticle performance in the cellular environment. This constitutes a huge research challenge due to difficulties for achieving a remote control within the human body. Here we report on the significant double role of the shape of ellipsoidal magnetic nanoparticles (nanorods) subjected to an external AC magnetic field: first, the heat release is increased due to the additional shape anisotropy; second, the rods dynamically reorientate in the orthogonal direction to the AC field direction...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922115/perilipin-5-fine-tunes-lipid-oxidation-to-metabolic-demand-and-protects-against-lipotoxicity-in-skeletal-muscle
#19
Claire Laurens, Virginie Bourlier, Aline Mairal, Katie Louche, Pierre-Marie Badin, Etienne Mouisel, Alexandra Montagner, André Marette, Angelo Tremblay, John S Weisnagel, Hervé Guillou, Dominique Langin, Denis R Joanisse, Cedric Moro
Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922088/analysis-of-four-toxic-metals-in-a-single-rice-seed-by-matrix-solid-phase-dispersion-inductively-coupled-plasma-mass-spectrometry
#20
Xiufen He, Lixia Chen, Xin Chen, Huamei Yu, Lixu Peng, Bingjun Han
Toxic metals in rice pose great risks to human health. Metal bioaccumulation in rice grains is a criterion of breeding. Rice breeding requires a sensitive method to determine metal content in single rice grains to assist the variety selection. In the present study, four toxic metals of arsenic (As), cadmium (Cd), chromium (Cr) and lead (Pb) in a single rice grain were determined by a simple and rapid method. The developed method is based on matrix solid phase dispersion using multi-wall carbon nanotubes (MWCNTs) as dispersing agent and analyzed by inductively coupled plasma mass spectrometry...
December 6, 2016: Scientific Reports
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