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https://www.readbyqxmd.com/read/28284560/computational-discovery-of-niclosamide-ethanolamine-a-repurposed-drug-candidate-that-reduces-growth-of-hepatocellular-carcinoma-cells-in-vitro-and-in-mice-by-inhibiting-cdc37-signaling
#1
Bin Chen, Wei Wei, Li Ma, Bin Yang, Ryan M Gill, Mei-Sze Chua, Atul J Butte, Samuel So
BACKGROUND & AIMS: Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS: We searched public databases of mRNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are downregulated in HCCs and reduce expression of genes upregulated in HCCs using a non-parametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic...
March 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28273762/natural-killer-cell-subpopulations-are-associated-with-mri-activity-in-a-relapsing-remitting-multiple-sclerosis-patient-cohort-from-australia
#2
P Caruana, K Lemmert, K Ribbons, R Lea, J Lechner-Scott
BACKGROUND: The importance of the innate immune system in multiple sclerosis (MS) is increasingly recognized and the role of natural killer (NK) cells in controlling autoimmunity may be an important modulator of disease activity. OBJECTIVE: To examine NK subsets in MS patients on different treatments and to evaluate the role of NK subsets as indicators for disease activity. METHODS: We measured NK subset levels in blood obtained from 110 relapsing-remitting MS patients...
November 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28273348/performance-evaluation-of-18-f-radioluminescence-microscopy-using-computational-simulation
#3
Qian Wang, Debanti Sengupta, Tae Jin Kim, Guillem Pratx
PURPOSE: Radioluminescence microscopy can visualize the distribution of beta-emitting radiotracers in live single cells with high resolution. Here, we perform a computational simulation of (18) F positron imaging using this modality to better understand how radioluminescence signals are formed and to assist in optimizing the experimental setup and image processing. METHODS: First, the transport of charged particles through the cell and scintillator and the resulting scintillation is modeled using the GEANT4 Monte-Carlo simulation...
March 8, 2017: Medical Physics
https://www.readbyqxmd.com/read/28253977/high-throughput-quantification-of-gfp-lc3-dots-by-automated-fluorescence-microscopy
#4
J M Bravo-San Pedro, F Pietrocola, V Sica, V Izzo, A Sauvat, O Kepp, M C Maiuri, G Kroemer, L Galluzzi
Macroautophagy is a specific variant of autophagy that involves a dedicated double-membraned organelle commonly known as autophagosome. Various methods have been developed to quantify the size of the autophagosomal compartment, which is an indirect indicator of macroautophagic responses, based on the peculiar ability of microtubule-associated protein 1 light chain 3 beta (MAP1LC3B; best known as LC3) to accumulate in forming autophagosomes upon maturation. One particularly convenient method to monitor the accumulation of mature LC3 within autophagosomes relies on a green fluorescent protein (GFP)-tagged variant of this protein and fluorescence microscopy...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28246291/-11-c-5-hydroxy-tryptophan-pet-for-assessment-of-islet-mass-during-progression-of-type-2-diabetes
#5
Lina Carlbom, Daniel Espes, Mark Lubberink, Mats Martinell, Lars Johansson, Håkan Ahlström, Per-Ola Carlsson, Olle Korsgren, Olof Eriksson
[(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28223128/a-screening-assay-for-the-identification-of-host-cell-requirements-and-antiviral-targets-for-hepatitis-d-virus-infection
#6
Bettina Buchmann, Katinka Döhner, Thomas Schirdewahn, Beate Sodeik, Michael P Manns, Heiner Wedemeyer, Sandra Ciesek, Thomas von Hahn
Hepatitis delta virus (HDV) is a minimalistic satellite virus of hepatitis B virus (HBV). HBV/HDV co-infection, i.e. "hepatitis D", is the most severe form of viral hepatitis. No effective therapy for HDV infection is available partly due to the fact that HDV is a highly host-dependent virus devoid of any potentially drugable enzyme encoded in its small genome. In this study we present a semi-automated method to evaluate HDV infection and replication under the influence of different drugs. We utilized a Huh-7/hNTCP cell culture based system in a 96-well plate format, an automated microscope and image acquisition as well as analysis with the CellProfiler software to quantify the impact of these drugs on HDV infection...
February 20, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28212878/evaluation-of-macular-vascular-abnormalities-identified-by-optical-coherence-tomography-angiography-in-sickle-cell-disease
#7
Ian C Han, Mongkol Tadarati, Katia D Pacheco, Adrienne W Scott
PURPOSE: To evaluate macular vascular flow abnormalities identified by optical coherence tomography angiography (OCT-A) in patients with various sickle cell genotypes. DESIGN: Prospective, observational case series. METHODS: This is a single institution case series of adult patients with various sickle cell genotypes. All patients underwent macular OCT-A (Avanti RTVue XR, Optovue Inc, Fremont, CA). Images were analyzed qualitatively for areas of flow loss and quantitatively for measures of foveal avascular area, parafoveal flow, and vascular density...
February 14, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#8
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197211/therapeutic-effects-of-fermented-flax-seed-oil-on-nc-nga-mice-with-atopic-dermatitis-like-skin-lesions
#9
Joonhyoung Yang, Sangyeon Min, Seungug Hong
Background. Atopic Dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Objective. This experiment aimed to study the effects of Fermented Flax Seed Oil (FFSO) on symptoms such as redness, eczema, and pruritus induced by AD. Materials and Methods. AD-induced NC/Nga mice were used to observe the immunological and therapeutic effects of FFSO on skin in vivo. Raw 264.7 cells were used to investigate the effects of FFSO in cells. Fc receptor expression and concentration of beta-hexosaminidase were measured...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28196319/common-skin-conditions-in-children-congenital-melanocytic-nevi-and-infantile-hemangiomas
#10
Brian Z Rayala, Dean S Morrell
Congenital melanocytic nevi (CMN) are hamartomas present at birth that are composed of nevomelanocytes and thought to originate from faulty migration of precursor melanocytes in the neural crest. Classification is based on projected adult size of the lesion. CMN size correlates positively with risk of melanoma and neurocutaneous melanocytosis. Management requires a patient-centered approach that weighs the risks and benefits of and alternatives to complete removal. All children with large and giant CMN, regardless of surgical status, should be monitored closely and undergo periodic skin examination...
February 2017: FP Essentials
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#11
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28174113/involvement-of-glun2b-subunit-containing-n-methyl-d-aspartate-nmda-receptors-in-mediating-the-acute-and-chronic-synaptotoxic-effects-of-oligomeric-amyloid-beta-a%C3%AE-in-murine-models-of-alzheimer-s-disease-ad
#12
Gerhard Rammes, Corinna Mattusch, Matthias Wulff, Franziska Seeser, Matthias Kreuzer, Kaichuan Zhu, Jan M Deussing, Jochen Herms, Chris G Parsons
To elucidate whether a permanent reduction of the GluN2B subunit affects the pathology of Alzheimer's disease (AD), we cross-bred mice heterozygous for GluN2B receptors in the forebrain (hetGluN2B) with a mouse model for AD carrying a mutated amyloid precursor protein with the Swedish and Arctic mutation (mAPP) resulting in a hetGluN2B/mAPP transgenic. By means of voltage-sensitive dye imaging (VSDI) in the di-synaptic hippocampal pathway and the recording of field excitatory postsynaptic potentials (fEPSPs), hippocampal slices of all genotypes (WT, hetGluN2B, mAPP and hetGluN2B/mAPP, age 9-18 months) were tested for spatiotemporal activity propagation and LTP induction...
February 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28161954/two-photon-dye-cocktail-for-dual-color-3d-imaging-of-pancreatic-beta-and-alpha-cells-in-live-islets
#13
Bikram Keshari Agrawalla, Hyo Won Lee, Wut-Hmone Phue, Anandhkumar Raju, Jong-Jin Kim, Hwan Myung Kim, Nam-Young Kang, Young-Tae Chang
Insulin-secreting beta cells together with glucagon-producing alpha cells play an essential role in maintaining the optimal blood glucose level in the body, so the development of selective probes for imaging of these cell types in live islets is highly desired. Herein we report the development of a 2-glucosamine-based two-photon fluorescent probe, TP-β, that is suitable for imaging of beta cells in live pancreatic islets from mice. Flow cytometry studies confirmed that TP-β is suitable for isolation of primary beta cells...
February 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28134307/fingolimod-limits-acute-a%C3%AE-neurotoxicity-and-promotes-synaptic-versus-extrasynaptic-nmda-receptor-functionality-in-hippocampal-neurons
#14
Pooja Joshi, Martina Gabrielli, Luisa Ponzoni, Silvia Pelucchi, Matteo Stravalaci, Marten Beeg, Sonia Mazzitelli, Daniela Braida, Mariaelvina Sala, Enrica Boda, Annalisa Buffo, Marco Gobbi, Fabrizio Gardoni, Michela Matteoli, Elena Marcello, Claudia Verderio
Fingolimod, also known as FTY720, is an analogue of the sphingolipid sphingosine, which has been proved to be neuroprotective in rodent models of Alzheimer's disease (AD). Several cellular and molecular targets underlying the neuroprotective effects of FTY720 have been recently identified. However, whether the drug directly protects neurons from toxicity of amyloid-beta (Aβ) still remains poorly defined. Using a combination of biochemical assays, live imaging and electrophysiology we demonstrate that FTY720 induces a rapid increase in GLUN2A-containing neuroprotective NMDARs on the surface of dendritic spines in cultured hippocampal neurons...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28133749/depth-dependent-concentrations-of-hematopoietic-stem-cells-in-the-adult-skeleton-implications-for-active-marrow-dosimetry
#15
Amy M Geyer, Bryan C Schwarz, Shannon E O'Reilly, Robert F Hobbs, George Sgouros, Wesley E Bolch
PURPOSE: The hematopoietically active (or red) bone marrow is the target tissue assigned in skeletal dosimetry models for assessment of stochastic effects (leukemia induction) as well as tissue reactions (marrow toxicity). Active marrow, however, is in reality a surrogate tissue region for specific cell populations, namely the hematopoietic stem and progenitor cells. Present models of active marrow dosimetry implicitly assume that these cells are uniformly localized throughout the marrow spaces of trabecular spongiosa...
February 2017: Medical Physics
https://www.readbyqxmd.com/read/28111350/antiarrhythmic-effects-of-interleukin-1-inhibition-after-myocardial-infarction
#16
Nicole M De Jesus, Lianguo Wang, Johnny Lai, Robert R Rigor, Samantha D Francis Stuart, Donald M Bers, Merry L Lindsey, Crystal M Ripplinger
BACKGROUND: Interleukin 1β (IL-1β) is a key regulator of the inflammatory response after myocardial infarction (MI) by modulating immune cell recruitment, cytokine production, and extracellular matrix turnover. Elevated levels of IL-1β are associated with adverse remodeling, and inhibition of IL-1 signaling after MI results in improved contractile function. OBJECTIVE: The goal of this study was to determine whether IL-1 signaling also contributes to post-MI arrhythmogenesis...
January 19, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28103285/radioiodinated-exendin-4-is-superior-to-the-radiometal-labelled-glucagon-like-peptide-1-receptor-probes-overcoming-their-high-kidney-uptake
#17
Tilman Läppchen, Roswitha Tönnesmann, Jos Eersels, Philipp T Meyer, Helmut R Maecke, Svetlana N Rylova
GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9-39) were studied in vitro using Ins-1E cells...
2017: PloS One
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#18
Rikke Kaae Kirk, Charles Pyke, Matthias G von Herrath, Jane Preuss Hasselby, Lars Pedersen, Pia Gottrup Mortensen, Lotte Bjerre Knudsen, Ken Coppieters
Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of T2D. Immunohistochemical studies for GLP-1R expression have previously been hampered by the use of unspecific polyclonal antibodies. This study used a new monoclonal antibody to assess GLP-1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP-4 inhibitor and 1 with a GLP-1R agonist treatment history...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28067253/whole-organ-and-islet-of-langerhans-dosimetry-for-calculation-of-absorbed-doses-resulting-from-imaging-with-radiolabeled-exendin
#19
Inge van der Kroon, Wietske Woliner-van der Weg, Maarten Brom, Lieke Joosten, Cathelijne Frielink, Mark W Konijnenberg, Eric P Visser, Martin Gotthardt
Radiolabeled exendin is used for non-invasive quantification of beta cells in the islets of Langerhans in vivo. High accumulation of radiolabeled exendin in the islets raised concerns about possible radiation-induced damage to these islets in man. In this work, islet absorbed doses resulting from exendin-imaging were calculated by combining whole organ dosimetry with small scale dosimetry for the islets. Our model contains the tissues with high accumulation of radiolabeled exendin: kidneys, pancreas and islets...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28034704/antioxidants-taken-orally-prior-to-diagnostic-radiation-exposure-can-prevent-dna-injury
#20
Nivethan Velauthapillai, Joe Barfett, Hussein Jaffer, David Mikulis, Kieran Murphy
PURPOSE: To evaluate efficacy of oral antioxidant treatment given to patients before radiologic procedures in reducing x-ray-induced DNA damage. MATERIALS AND METHODS: In a single-center prospective controlled trial, antioxidant treatment with 2 g ascorbate, 1.2 g N-acetylcysteine, 600 mg lipoic acid, and 30 mg beta carotene was given to 5 consecutive participants before undergoing clinically indicated technetium-99m methylene diphosphonate ((99m)Tc MDP) bone scans for cancer staging...
March 2017: Journal of Vascular and Interventional Radiology: JVIR
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