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https://www.readbyqxmd.com/read/28533737/the-alpha-1a-adrenergic-receptor-agonist-a61603-reduces-cardiac-polyunsaturated-fatty-acid-and-endocannabinoid-metabolites-associated-with-inflammation-in-vivo
#1
Monte S Willis, Amro Ilaiwy, Megan D Montgomery, Paul C Simpson, Brian C Jensen
INTRODUCTION: Alpha-1-adrenergic receptors (α1-ARs) are G-protein coupled receptors (GPCRs) with three highly homologous subtypes (α1A, α1B, and α1D). Of these three subtypes, only the α1A and α1B are expressed in the heart. Multiple pre-clinical models of heart injury demonstrate cardioprotective roles for the α1A. Non-selective α1-AR activation promotes glycolysis in the heart, but the functional α1-AR subtype and broader metabolic effects have not been studied. OBJECTIVES: Given the high metabolic demands of the heart and previous evidence indicating benefit from α1A activation, we chose to investigate the effects of α1A activation on the cardiac metabolome in vivo...
October 2016: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28531880/controlled-release-of-moxifloxacin-from-intraocular-lenses-modified-by-ar-plasma-assisted-grafting-with-amps-or-sbma-an-in-vitro-study
#2
A F R Pimenta, A P Vieira, R Colaço, B Saramago, M H Gil, P Coimbra, P Alves, D Bozukova, T R Correia, I J Correia, A J Guiomar, A P Serro
Intraocular lenses (IOLs) present an alternative for extended, local drug delivery in the prevention of post-operative acute endophthalmitis. In the present work, we modified the surface of a hydrophilic acrylic material, used for manufacturing of IOLs, through plasma-assisted grafting copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), with the aim of achieving a controlled and effective drug release. The material was loaded with moxifloxacin (MFX), a commonly used antibiotic for endophthalmitis prevention...
May 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28523947/potentiation-of-trap-6-induced-platelet-dense-granule-release-by-blockade-of-p2y12-signaling-with-mrs2395
#3
Annachiara Mitrugno, Rachel A Rigg, Nicole B Laschober, Anh T P Ngo, Jiaqing Pang, Craig D Williams, Joseph E Aslan, Owen J T McCarty
The release of ADP from platelet dense granules and its binding to platelet P2Y12 receptors is key to amplifying the initial hemostatic response and propagating thrombus formation. P2Y12 has thus emerged as a therapeutic target to safely and effectively prevent secondary thrombotic events in patients with acute coronary syndrome or a history of myocardial infarction. Pharmacological inhibition of P2Y12 receptors represents a useful approach to better understand the signaling mediated by these receptors and to elucidate the role of these receptors in a multitude of platelet hemostatic and thrombotic responses...
May 19, 2017: Platelets
https://www.readbyqxmd.com/read/28523577/ffa3-activation-stimulates-duodenal-bicarbonate-secretion-and-prevents-nsaid-induced-enteropathy-via-the-glp-2-pathway-in-rats
#4
Hyder Said, Yasutada Akiba, Kazuyuki Narimatsu, Koji Maruta, Ayaka Kuri, Ken-Ichi Iwamoto, Atsukazu Kuwahara, Jonathan D Kaunitz
BACKGROUND: Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO3(-) secretion...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28505588/hydroxylated-2-ethylhexyl-tetrabromobenzoate-isomers-in-house-dust-and-their-agonistic-potencies-with-several-nuclear-receptors
#5
Hui Peng, Jianxian Sun, David M V Saunders, Garry Codling, Steve Wiseman, Paul D Jones, John P Giesy
In the current study, by combining ultra-high resolution (UHR) MS(1) spectra, MS(2) spectra, and derivatization, three hydroxylated isomers of 2-ethylhexyl tetrabromobenzoate (OH-TBB) were identified in Firemaster(®) 550 and BZ-54 technical products. Also, a new LC-UHRMS method, using atmospheric pressure chemical ionization (APCI), was developed for simultaneous analysis of OH-TBB, TBB, hydroxylated bis(2-ethylhexyl)-tetrabromophthalate (OH-TBPH) and TBPH in 23 samples of dust collected from houses in Saskatoon, SK, Canada...
May 12, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28504694/the-prohibitin-repressive-interaction-with-e2f1-is-rapidly-inhibited-by-androgen-signalling-in-prostate-cancer-cells
#6
S Koushyar, G Economides, S Zaat, W Jiang, C L Bevan, D A Dart
Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities across several cellular compartments including mitochondria, cell membrane and the nucleus. PHB and the steroid-activated androgen receptor (AR) have an interplay where AR downregulates PHB, and PHB represses AR. Additionally, their cellular locations and chromatin interactions are in dynamic opposition. We investigated the mechanisms of cell cycle inhibition by PHB and how this is modulated by AR in prostate cancer. Using a prostate cancer cell line overexpressing PHB, we analysed the gene expression changes associated with PHB-mediated cell cycle arrest...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28491857/administration-of-zinc-against-arsenic-induced-nephrotoxicity-during-gestation-and-lactation-in-rat-model
#7
Davood Nasiry Zarrin Ghabaee, Fereshteh Talebpour Amiri, Amir Esmaeelnejad Moghaddam, Ali Reza Khalatbary, Mehryar Zargari
BACKGROUND: Free radicals production by toxicity of arsenic (Ar) is most important in the nephrotoxicity. There is accumulating evidence that zinc (Zn), has anti-oxidant properties. OBJECTIVES: The aim of present study was to evaluate protective and ameliorative effects of Zn against Ar-induced nephrotoxicity in rat pups during gestation and lactation. MATERIALS AND METHODS: Twenty-four adult pregnant wistar rats were randomly divided into four groups (n = 6)...
March 2017: Journal of Nephropathology
https://www.readbyqxmd.com/read/28490267/darolutamide-odm-201-for-the-treatment-of-prostate-cancer
#8
Neal D Shore
Androgen deprivation therapy (ADT) is a mainstay initial treatment for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to castration-resistant prostate cancer (CRPC) invariably occurs when patients do not succumb to another disease or comorbidity. Recognition that the androgen receptor (AR) axis continues to drive disease progression has led to the development of several AR-directed approved agents, including abiraterone acetate and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788), has completed early-phase clinical trials, and two global phase III trials are currently accruing patients...
May 24, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28487837/the-role-of-vitamin-d-in-allergic-rhinitis
#9
REVIEW
Hui-Qin Tian, Lei Cheng
Recent studies suggest that vitamin D is related to allergic rhinitis (AR). In this review, we first discuss the physiology and metabolism of vitamin D, then we review the function of vitamin D in the immune system, and above all, we highlight the current research regarding the role of vitamin D in AR. Finally, we find that there are both experimental and clinical studies showing that vitamin D is associated with AR, although the results are not consistent and even conflicting. Evidences from those clinical studies show a slightly tendency that serum vitamin D level might be inversely associated with the risk of AR...
April 2017: Asia Pacific Allergy
https://www.readbyqxmd.com/read/28487342/calcium-calmodulin-dependent-protein-kinase-ii-activity-persists-during-chronic-%C3%AE-adrenoceptor-blockade-in-experimental-and-human-heart-failure
#10
Matthias Dewenter, Stefan Neef, Christiane Vettel, Simon Lämmle, Christina Beushausen, Laura C Zelarayan, Sylvia Katz, Albert von der Lieth, Stefanie Meyer-Roxlau, Silvio Weber, Thomas Wieland, Samuel Sossalla, Johannes Backs, Joan H Brown, Lars S Maier, Ali El-Armouche
BACKGROUND: Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF...
May 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28485963/high-useful-yield-and-isotopic-analysis-of-uranium-by-resonance-ionization-mass-spectrometry
#11
Michael R Savina, Brett H Isselhardt, Andrew Kucher, Reto Trappitsch, Bruce V King, David Ruddle, Raja Gopal, Ian Hutcheon
Useful yields from resonance ionization mass spectrometry can be extremely high compared to other mass spectrometry techniques, but uranium analysis shows strong matrix effects arising from the tendency of uranium to form strongly bound oxide molecules that do not dissociate appreciably on energetic ion bombardment. We demonstrate a useful yield of 24% for metallic uranium. Modeling the laser ionization and ion transmission processes shows that the high useful yield is attributable to a high ion fraction achieved by resonance ionization...
May 24, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28485785/study-on-the-influence-of-metformin-on-castration-resistant-prostate-cancer-pc-3-cell-line-biological-behavior-by-its-inhibition-on-plc%C3%AE%C2%B5-gene-mediated-notch1-hes-and-androgen-receptor-signaling-pathway
#12
Y Yang, X-H Wu
OBJECTIVE: To study the regulation of metformin on the biological behaviors of the castration-resistant prostate cancer (CRPC) PC-3 cell such as proliferation, invasion, apoptosis through influencing Notch1/Hes and androgen receptor (AR) signaling pathway activity by its inhibition on the expression of PLCε gene. MATERIALS AND METHODS: Human prostate cancer-3 (PC-3) cell line was divided into PC-3 cell line (group A), PC-3 cell line + metformin (10 mM) (group B), PC-3 cell line + metformin (20 mM) (group C), PLCε gene knockout cell line (group D), PLCε knockout cell line + metformin (10 mM)_ (group E) and PLCε knockout cell line + metformin (20 mM) (group F), which were respectively tested at 24 h, 48 h and 72 h, and five duplicate wells were set at each time point in each group...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28484763/electron-stimulated-desorption-from-condensed-pyrimidine-and-pyridazine
#13
L Ellis-Gibbings, A D Bass, P Cloutier, G García, L Sanche
Low energy electron (LEE) interactions and the formation of transient negative ions play a dominant role in radiation-induced dissociation of condensed-phase biomolecules (e.g. in radiotherapy). Here we present data on the LEE-induced dissociation and desorption of the DNA/RNA-base and radiosensitizing agent analogues pyrimidine and pyridazine. Vapors of each molecule were condensed on either a Pt or Ar substrate to form a multilayer film or a submonolayer molecular target, respectively. These were irradiated with electrons of 0-80 eV and the desorbing anionic and cationic fragments analysed via time of flight mass spectrometry...
May 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28481074/atomic-resolution-transmission-electron-microscopic-movies-for-study-of-organic-molecules-assemblies-and-reactions-the-first-10-years-of-development
#14
Eiichi Nakamura
A molecule is a quantum mechanical entity. "Watching motions and reactions of a molecule with our eyes" has therefore been a dream of chemists for a century. This dream has come true with the aid of the movies of atomic-resolution transmission electron microscopic (AR-TEM) molecular images through real-time observation of dynamic motions of single organic molecules (denoted hereafter as single-molecule atomic-resolution real-time (SMART) TEM imaging). Since 2007, we have reported movies of a variety of single organic molecules, organometallic molecules, and their assemblies, which are rotating, stretching, and reacting...
May 8, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28481057/mapping-and-comparing-bacterial-microbiota-in-the-sinonasal-cavity-of-healthy-allergic-rhinitis-and-chronic-rhinosinusitis-subjects
#15
Devyani Lal, Paul Keim, Josie Delisle, Bridget Barker, Matthew A Rank, Nicholas Chia, James M Schupp, John D Gillece, Emily K Cope
BACKGROUND: The role of microbiota in sinonasal inflammation can be further understood by targeted sampling of healthy and diseased subjects. We compared the microbiota of the middle meatus (MM) and inferior meatus (IM) in healthy, allergic rhinitis (AR), and chronic rhinosinusitis (CRS) subjects to characterize intrasubject, intersubject, and intergroup differences. METHODS: Subjects were recruited in the office, and characterized into healthy, AR, and CRS groups...
May 8, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28480649/regional-difference-of-causative-pollen-in-children-with-allergic-rhinitis
#16
Myongsoon Sung, Sung Won Kim, Jeong Hee Kim, Dae Hyun Lim
The aim of this study was to investigate role of common pollen in Korean school-aged children with allergic rhinitis (AR) in 5 provinces (Incheon Metropolitan City-Gyeonggi Province, Chungcheongbuk-do, Gwangju Metropolitan City, Busan Metropolitan City, and Jeju Special Self-Governing Province), using a questionnaire and skin prick test, and to assess the differences among the residential regions. Among the enrolled 14,678 total children, 1,641 (22.0%) had AR. The sensitization rate to pollen (38.7%) was the second highest among examined allergens and significant differences were in the sensitization rates to trees, weeds, and grasses among the 5 provinces (P < 0...
June 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28473535/androgen-receptor-variant-ar-v9-is-co-expressed-with-ar-v7-in-prostate-cancer-metastases-and-predicts-abiraterone-resistance
#17
Manish Kohli, Yeung Ho, David W Hillman, Jamie L Van Etten, Christine Henzler, Rendong Yang, Jame M Sperger, Yingming Li, Elizabeth Tseng, Ting Hon, Tyson Clark, Winston Tan, Rachel E Carlson, Liguo Wang, Hugues Sicotte, Ho Thai, Rafael Jimenez, Haojie Huang, Peter T Vedell, Bruce W Eckloff, J Fernando Quevedo, Henry C Pitot, Brian Costello, Jin Jen, Eric D Wieben, Kevin A T Silverstein, Joshua M Lang, Liewei Wang, Scott M Dehm
Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies.  Accordingly, efforts are underway to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC).  The purpose of this study was to understand whether other AR variants may be co-expressed with AR-V7 and promote resistance to AR-targeted therapies.<br /><br /> Experimental Design:  We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models...
May 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28473532/novel-androgen-receptor-co-regulator-grhl2-exerts-both-oncogenic-and-anti-metastatic-functions-in-prostate-cancer
#18
Steve Paltoglou, Rajdeep Das, Scott L Townley, Theresa Hickey, Gerard Tarulli, Isabel Coutinho, Rayzel C Fernandes, Adrienne Hanson, Iza Denis, Jason Carroll, Scott M Dehm, Ganesh V Raj, Steve Plymate, Wayne D Tilley, Luke A Selth
Alterations to the expression and activity of androgen receptor (AR) co-regulators in prostate cancer is an important mechanism driving disease progression and therapy resistance. Using a novel proteomic technique, we identified a new AR co-regulator, the transcription factor Grainyhead-like 2 (GRHL2), and demonstrated its essential role in the oncogenic AR signaling axis. GRHL2 colocalized with AR in prostate tumors and was frequently amplified and upregulated in prostate cancer. Importantly, GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR's transcriptional activity, and co-located with AR at specific sites on chromatin to regulate genes relevant to disease progression...
May 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28472366/androgen-receptor-gene-status-in-plasma-dna-associates-with-worse-outcome-on-enzalutamide-or-abiraterone-for-castration-resistant-prostate-cancer-a-multi-institution-correlative-biomarker-study
#19
V Conteduca, D Wetterskog, M T A Sharabiani, E Grande, M P Fernandez-Perez, A Jayaram, S Salvi, D Castellano, A Romanel, C Lolli, V Casadio, G Gurioli, D Amadori, A Font, S Vazquez-Estevez, A González Del Alba, B Mellado, O Fernandez-Calvo, M J Méndez-Vidal, M A Climent, I Duran, E Gallardo, A Rodriguez, C Santander, M I Sáez, J Puente, D Gasi Tandefelt, A Wingate, D Dearnaley, F Demichelis, U De Giorgi, E Gonzalez-Billalabeitia, G Attard
Background: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. Methods: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data...
May 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28470764/glyoxalase-2-drives-tumorigenesis-in-human-prostate-cells-in-a-mechanism-involving-androgen-receptor-and-p53-p21-axis
#20
Cinzia Antognelli, Ivana Ferri, Guido Bellezza, Paola Siccu, Harold D Love, Vincenzo Nicola Talesa, Angelo Sidoni
Glyoxalase 2 (Glo2), a metabolic enzyme, is overexpressed in some human cancers which suggests this enzyme may play a role in human tumorigenesis. In prostate cancer (PCa) the role of Glo2 has been scarcely investigated and there are no studies addressing a causative involvement of this protein in this neoplasia. Here we examined the immunohistochemical profile of Glo2 in human PCa and benign adjacent tissues and investigated Glo2 involvement in PCa development in human prostate cell lines. PCa and matched adjacent normal tissues were obtained from paraffin sections of primary PCa from 20 patients who had undergone radical prostatectomy...
May 4, 2017: Molecular Carcinogenesis
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