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https://www.readbyqxmd.com/read/28092764/common-deregulated-gene-expression-profiles-and-morphological-changes-in-developing-zebrafish-larvae-exposed-to-environmental-relevant-high-to-low-concentrations-of-glucocorticoids
#1
Qiyu Chen, Caixia Li, Zhiyuan Gong, Eric Chun Yong Chan, Shane A Snyder, Siew Hong Lam
Synthetic glucocorticoids have been detected in environmental waters and their biological potency have raised concerns of their impact on aquatic vertebrates especially fish. In this study, developing zebrafish larvae exposed to representative glucocorticoids (dexamethasone, prednisolone and triamcinolone) at 50 pM to 50 nM from 3 h post-fertilisation to 5 days post-fertilisation were investigated. Microarray analysis identified 1255, 1531, and 2380 gene probes, which correspondingly mapped to 660, 882 and 1238 human/rodent homologs, as deregulated by dexamethasone, prednisolone and triamcinolone, respectively...
January 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#2
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28087637/retinoic-acid-receptor-regulation-of-epimorphic-and-homeostatic-regeneration-in-the-axolotl
#3
Matthew Nguyen, Pankhuri Singhal, Judith Piet, Sandra J Shefelbine, Malcolm Maden, S Randal Voss, James R Monaghan
Salamanders are capable of regenerating amputated limbs by generating a mass of lineage-restricted cells called a blastema. Blastemas only generate structures distal to their origin unless treated with retinoic acid (RA), which results in proximodistal (PD) limb duplications. Little is known about the transcriptional network that regulates PD duplication. In this study, we target specific retinoic acid receptors (RARs) to either PD duplicate (RA treatment or RARγ agonist) or truncate (RARβ antagonist) regenerating limbs...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28073161/the-pnpla3-i148m-variant-modulates-the-fibrogenic-phenotype-of-human-hepatic-stellate-cells
#4
Francesca Virginia Bruschi, Thierry Claudel, Matteo Tardelli, Alessandra Caligiuri, Thomas M Stulnig, Fabio Marra, Michael Trauner
: The genetic polymorphism I148M of PNPLA3 is robustly associated with hepatic steatosis and its progression to steatohepatitis, fibrosis and cancer. Hepatic stellate cells (HSCs) are key players in the development of liver fibrosis, but the role of PNPLA3 and its variant I148M in this process is poorly understood. Here we analyzed the expression of PNPLA3 during human HSC activation and thereby explored how a PNPLA3 variant impacts on hepatic fibrogenesis. We show that PNPLA3 gene and protein expression increase during the early phases of activation and remain elevated in fully activated HSCs (p<0...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28054069/challenge-and-perspective-the-relevance-of-ultraviolet-uv-radiation-and-the-vitamin-d-endocrine-system-vdes-for-psoriasis-and-other-inflammatory-skin-diseases
#5
Jörg Reichrath, Roman Saternus, Thomas Vogt
During evolution, the ability of many organisms to synthesize vitamin D photochemically represented, and still represents, a major driving factor for the development of life on earth. In humans because not more than 10-20% of the requirement of vitamin D can be satisfied by the diet (under most living conditions in the US and Europe), the remaining 80-90% need to be photochemically synthesized in the skin through the action of solar or artificial ultraviolet-B (UV-B) radiation. The skin is a key organ of the human body's vitamin D endocrine system (VDES), representing both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites...
January 5, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28017127/marginal-vitamin-a-deficiency-exacerbates-memory-deficits-following-a%C3%AE-1-42-injection-in-rats
#6
Jiaying Zeng, Tingyu Li, Ming Gong, Wei Jiang, Ting Yang, Jie Chen
BACKGROUND: Although clinical vitamin A deficiency (VAD), which is a public health problem throughout the developing world, has been well controlled, marginal vitamin A deficiency (MVAD) is far more prevalent, especially among pregnant women and preschool children in China. Increasing evidence suggests that VAD is involved in the pathogenesis of Alzheimer's disease (AD). However, whether MVAD, beginning early in life, increases the risk of developing AD has yet to be determined. OBJECTIVE: The goal of this study was to investigate the long-term effects of MVAD on the pathogenesis of AD in rats...
December 23, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/28013364/rest-activity-patterns-and-falls-and-fractures-in-older-men
#7
Tara S Rogers, Terri L Blackwell, Nancy E Lane, Greg Tranah, Eric S Orwoll, Jane A Cauley, Sonia Ancoli-Israel, Katie L Stone, Steven R Cummings, Peggy M Cawthon
: Dysregulated rest-activity rhythm (RAR) patterns have been associated with several health conditions in older adults. This study showed that later acrophase was associated with a modestly greater risk of falls but not fractures in elderly men. Associations between dysregulated RAR patterns and osteoporosis risk warrant further investigation. PURPOSE: The purpose of this study was to investigate the relationship between rest-activity rhythm (RAR) patterns and risk of falls/fractures in older men...
December 24, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/28009151/comparing-conventional-laparoscopic-to-robotic-assisted-extended-pelvic-lymph-node-dissection-in-men-with-intermediate-and-high-risk-prostate-cancer-a-matched-pair-analysis
#8
Simone Albisinni, Fouad Aoun, Dam LE Dinh, Marc Zanaty, Eric Hawaux, Alexandre Peltier, Roland VAN Velthoven
BACKGROUND: In intermediate and high-risk prostate cancer patients, a robotic-assisted approach is increasingly being used for prostatectomy and extended pelvic lymph node dissection (ePLND). This is reducing the number of conventional laparoscopic radical prostatectomies (LR P) and laparoscopic ePLNDs for prostate cancer in Europe. Aim of this study is to compare laparoscopic ePLND to robotic-assisted ePLND in a cohort of patients with intermediate and high risk prostate cancer. METHODS: We performed a matched-pair analysis matching 1:1 70 patients who underwent LRP+ePLND (2004-2009) to 70 who underwent RAR P+ePLND (2010-2014)...
February 2017: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/28009147/ten-year-experience-of-robot-assisted-radical-prostatectomy-the-road-from-cherry-picking-to-standard-procedure
#9
Jonas Schiffmann, Alexander Haese, Katharina Boehm, Georg Salomon, Thomas Steuber, Hans Heinzer, Hartwig Huland, Markus Graefen, Pierre I Karakiewicz
BACKGROUND: Patients treated with robot-assisted radical prostatectomy (RARP) are frequently selected according to more favorable characteristics. Such patient selection might decrease according to increasing experience. METHODS: We relied on the Martini Clinic Prostate Cancer Center database and focused on patients treated with RARP between 2004 and 2013. Differences in clinical, pathological and surgical characteristics at RARP over time (2004-2010, 2011-2012 and 2013) were assessed...
February 2017: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/28007475/mechanisms-of-retinoic-acid-signaling-during-cardiogenesis
#10
REVIEW
Sonia Stefanovic, Stéphane Zaffran
Substantial experimental and epidemiological data have highlighted the interplay between nutritional and genetic factors in the development of congenital heart defects. Retinoic acid (RA), a derivative of vitamin A, plays a key role during vertebrate development including the formation of the heart. Retinoids bind to RA and retinoid X receptors (RARs and RXRs) which then regulate tissue-specific genes. Here, we will focus on the roles of RA signaling and receptors in gene regulation during cardiogenesis, and the consequence of deregulated retinoid signaling on heart formation and congenital heart defects...
December 19, 2016: Mechanisms of Development
https://www.readbyqxmd.com/read/28000295/drug-availability-adjustments-in-population-based-studies-of-prescription-opioid-abuse
#11
Alex Secora, James Phillip Trinidad, Rongmei Zhang, Rajdeep Gill, Gerald Dal Pan
PURPOSE: Population-based prescription opioid abuse studies in which one drug is compared to another, or drugs are compared across time, often account for the availability of those drugs in the community. The objective of this investigation is to assess consistency in the relative abuse ratios (RARs) across different approaches for adjusting for drug availability. METHODS: For the years 2004 through 2010, RARs for each of four prescription opioids (hydrocodone, oxycodone, hydromorphone, and morphine) were calculated using negative binomial regression...
December 21, 2016: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/27996177/peroxisome-proliferator-activated-receptor-%C3%AE-%C3%AE-inhibits-human-neuroblastoma-cell-tumorigenesis-by-inducing-p53-and-sox2-mediated-cell-differentiation
#12
Pei-Li Yao, Liping Chen, Tomasz P Dobrzański, Bokai Zhu, Boo-Hyon Kang, Rolf Müller, Frank J Gonzalez, Jeffrey M Peters
Neuroblastoma is a common childhood cancer typically treated by inducing differentiation with retinoic acid (RA). Peroxisome proliferator-activated receptor-β/δ, (PPARβ/δ) is known to promote terminal differentiation of many cell types. In the present study, PPARβ/δ was over-expressed in three human neuroblastoma cell lines, NGP, SK-N-BE(2) and IMR-32, that exhibit high, medium and low sensitivity, respectively, to retinoic acid-induced differentiation to determine if PPARβ/δ and retinoic acid receptors (RARs) could be jointly targeted to increase the efficacy of treatment...
December 20, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27994837/treatment-of-refractory-anemia-with-ring-sideroblasts-associated-with-marked-thrombocytosis-with-lenalidomide-in-a-patient-testing-negative-for-5q-deletion-and-jak2-v617f-and-mpl-w515k-l-mutations
#13
Ryan Keen, Jeremy Pantin, Natasha Savage, Paul M Dainer
Refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T) is a hematologic malignancy that often results in transfusion dependency and a hypercoagulable state. This rare disease currently lacks formal guidelines for treatment; however, various case reports have demonstrated efficacy in the use of lenalidomide. This immunomodulatory drug has shown promise in patients with 5q deletions, with reports of achieving transfusion independence and normalization of platelet counts. Herein we present the case of a 68-year-old African American woman with RARS-T who tested negative for 5q deletion and JAK2 V617F and MPL W515K/L mutations...
November 2, 2016: Hematology Reports
https://www.readbyqxmd.com/read/27992436/transcriptomic-analysis-shows-decreased-cortical-expression-of-nr4a1-nr4a2-and-rxrb-in-schizophrenia-and-provides-evidence-for-nuclear-receptor-dysregulation
#14
Susan M Corley, Shan-Yuan Tsai, Marc R Wilkins, Cynthia Shannon Weickert
Many genes are differentially expressed in the cortex of people with schizophrenia, implicating factors that control transcription more generally. Hormone nuclear receptors dimerize to coordinate context-dependent changes in gene expression. We hypothesized that members of two families of nuclear receptors (NR4As), and retinoid receptors (RARs and RXRs), are altered in the dorsal lateral prefrontal cortex (DLPFC) of people with schizophrenia. We used next generation sequencing and then qPCR analysis to test for changes in mRNA levels for transcripts encoding nuclear receptors: orphan nuclear receptors (3 in the NR4A, 3 in the RAR, 3 in the RXR families and KLF4) in total RNA extracted from the DLPFC from people with schizophrenia compared to controls (n = 74)...
2016: PloS One
https://www.readbyqxmd.com/read/27973560/identification-of-the-functional-variant-s-that-explain-the-low-density-lipoprotein-receptor-ldlr-gwas-snp-rs6511720-association-with-lower-ldl-c-and-risk-of-chd
#15
Roaa Hani Fairoozy, Jon White, Jutta Palmen, Anastasia Z Kalea, Steve E Humphries
BACKGROUND: The Low-Density Lipoprotein Receptor (LDLR) SNP rs6511720 (G>T), located in intron-1 of the gene, has been identified in genome-wide association studies (GWAS) as being associated with lower plasma levels of LDL-C and a lower risk of coronary heart disease (CHD). Whether or not rs6511720 is itself functional or a marker for a functional variant elsewhere in the gene is not known. METHODS: The association of LDLR SNP rs6511720 with incidence of CHD and levels of LDL-C was determined by reference to CARDIoGRAM, C4D and Global lipids genetics consortium (GLGC) data...
2016: PloS One
https://www.readbyqxmd.com/read/27964926/retinoic-acid-receptor-signalling-directly-regulates-osteoblast-and-adipocyte-differentiation-from-mesenchymal-progenitor-cells
#16
A C Green, P Kocovski, T Jovic, M K Walia, R A S Chandraratna, T J Martin, E K Baker, L E Purton
Low and high serum retinol levels are associated with increased fracture risk and poor bone health. We recently showed retinoic acid receptors (RARs) are negative regulators of osteoclastogenesis. Here we show RARs are also negative regulators of osteoblast and adipocyte differentiation. The pan-RAR agonist, all-trans retinoic acid (ATRA), directly inhibited differentiation and mineralisation of early osteoprogenitors and impaired the differentiation of more mature osteoblast populations. In contrast, the pan-RAR antagonist, IRX4310, accelerated differentiation of early osteoprogenitors...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27957850/comparative-toxicogenomic-responses-to-the-flame-retardant-mitp-in-developing-zebrafish
#17
Derik E Haggard, Siba R Das, Robert L Tanguay
Monosubstituted isopropylated triaryl phosphate (mITP) is a major component of Firemaster 550, an additive flame retardant mixture commonly used in polyurethane foams. Developmental toxicity studies in zebrafish established mITP as the most toxic component of FM 550, which causes pericardial edema and heart looping failure. Mechanistic studies showed that mITP is an aryl hydrocarbon receptor (AhR) ligand; however, the cardiotoxic effects of mITP were independent of the AhR. We performed comparative whole genome transcriptomics in wild-type and ahr2(hu3335) zebrafish, which lack functional ahr2, to identify transcriptional signatures causally involved in the mechanism of mITP-induced cardiotoxicity...
December 13, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27937121/statistical-inference-for-response-adaptive-randomization-procedures-with-adjusted-optimal-allocation-proportions
#18
Hongjian Zhu
Seamless phase II/III clinical trials have attracted increasing attention recently. They mainly use Bayesian response adaptive randomization (RAR) designs. There has been little research into seamless clinical trials using frequentist RAR designs because of the difficulty in performing valid statistical inference following this procedure. The well-designed frequentist RAR designs can target theoretically optimal allocation proportions, and they have explicit asymptotic results. In this paper, we study the asymptotic properties of frequentist RAR designs with adjusted target allocation proportions, and investigate statistical inference for this procedure...
December 12, 2016: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/27933608/assessing-fear-learning-via-conditioned-respiratory-amplitude-responses
#19
Giuseppe Castegnetti, Athina Tzovara, Matthias Staib, Samuel Gerster, Dominik R Bach
Respiratory physiology is influenced by cognitive processes. It has been suggested that some cognitive states may be inferred from respiration amplitude responses (RAR) after external events. Here, we investigate whether RAR allow assessment of fear memory in cued fear conditioning, an experimental model of aversive learning. To this end, we built on a previously developed psychophysiological model (PsPM) of RAR, which regards interpolated RAR time series as the output of a linear time invariant system. We first establish that average RAR after CS+ and CS- are different...
December 8, 2016: Psychophysiology
https://www.readbyqxmd.com/read/27930681/transcriptomic-changes-in-liver-of-young-bulls-caused-by-diets-low-in-mineral-and-protein-contents-and-supplemented-with-n-3-fatty-acids-and-conjugated-linoleic-acid
#20
Sara Pegolo, Alessio Cecchinato, Núria Mach, Massimiliano Babbucci, Marianna Pauletto, Luca Bargelloni, Stefano Schiavon, Giovanni Bittante
The aim of the present study was to identify transcriptional modifications and regulatory networks accounting for physiological and metabolic responses to specific nutrients in the liver of young Belgian Blue × Holstein bulls using RNA-sequencing. A larger trial has been carried out in which animals were fed with different diets: 1] a conventional diet; 2] a low-protein/low-mineral diet (low-impact diet) and 3] a diet enriched in n-3 fatty acids (FAs), conjugated linoleic acid (CLA) and vitamin E (nutraceutical diet)...
2016: PloS One
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