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https://www.readbyqxmd.com/read/28935977/zebrafish-in-vivo-screening-for-compounds-amplifying-hematopoietic-stem-and-progenitor-cells-preclinical-validation-in-human-cd34-stem-and-progenitor-cells
#1
Guruchandar Arulmozhivarman, Martin Kräter, Manja Wobus, Jens Friedrichs, Elham Pishali Bejestani, Katrin Müller, Katrin Lambert, Dimitra Alexopoulou, Andreas Dahl, Martin Stöter, Marc Bickle, Nona Shayegi, Jochen Hampe, Friedrich Stölzel, Michael Brand, Malte von Bonin, Martin Bornhäuser
The identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28930551/uremic-toxins-are-conditional-danger-or-homeostasis-associated-molecular-patterns
#2
Yu Sun, Candice Johnson, Jun Zhou, Luqiao Wang, Ya-Feng Li, Yifan Lu, Gayani Nanayakkara, Hangfei Fu, Ying Shao, Claudette Sanchez, William Y Yang, Xin Wang, Eric T Choi, Rongshan Li, Hong Wang, Xiao-Feng Yang
We mined novel uremic toxin (UT) metabolomics/gene databases, and analyzed the expression changes of UT receptors and UT synthases in chronic kidney disease (CKD) and cardiovascular disease (CVD). We made the following observations: 1) UTs represent only 1/80(th) of human serum small-molecule metabolome; 2) Some UTs are increased in CKD and CVD; 3) UTs either induce or suppress the expression of inflammatory molecules; 4) The expression of UT genes is significantly modulated in CKD patients, and coronary artery disease (CAD) patients; 5) The expression of UT genes is upregulated by caspase-1 and TNF-alpha pathways but is inhibited in regulatory T cells...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28917245/a-single-nucleotide-polymorphism-in-transferrin-is-associated-with-soluble-transferrin-receptor-in-chinese-adolescents
#3
Wei Piao, Li Wang, Ting Zhang, Zhen Wang, Shaofang Shangguan, Jing Sun, Junsheng Huo
BACKGROUND AND OBJECTIVES: Associations between genetic variants in the hepcidin regulation pathway and iron status have been reported in previous studies. Most of these studies were conducted in populations of European descent and relatively few studies have been conducted in Chinese populations. In this study, we evaluated associations between single-nucleotide polymorphisms (SNPs) in the hepcidin regulation pathway, serum ferritin (SF) and soluble transferrin receptor (sTfR) in Chinese adolescents...
2017: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28911864/multiscale-approach-to-the-activation-and-phosphotransfer-mechanism-of-cpxa-histidine-kinase-reveals-a-tight-coupling-between-conformational-and-chemical-steps
#4
Franco Marsico, Osvaldo Burastero, Lucas A Defelipe, Elias Daniel Lopez, Mehrnoosh Arrar, Adrián G Turjanski, Marcelo A Marti
Sensor histidine kinases (SHKs) are an integral component of the molecular machinery that permits bacteria to adapt to widely changing environmental conditions. CpxA, an extensively studied SHK, is a multidomain homodimeric protein with each subunit consisting of a periplasmic sensor domain, a transmembrane domain, a signal-transducing HAMP domain, a dimerization and histidine phospho-acceptor sub-domain (DHp) and a catalytic and ATP-binding subdomain (CA). The key activation event involves the rearrangement of the HAMP-DHp helical core and translation of the CA towards the acceptor histidine, which presumably results in a autokinase-competent complex...
September 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28898874/associations-between-liver-enzyme-levels-and-parameters-of-the-metabolic-syndrome-in-obese-children
#5
Christiane S Hampe, Michele L Shaffer, Christian L Roth
BACKGROUND: Obesity is strongly associated with insulin resistance, hypertension, dyslipidemia, and therefore risk for metabolic syndrome (MetS), which is an increasing problem in youth. The potential role of elevated liver enzyme levels in this context needs to be further investigated. METHODS: This paper provides a post hoc analysis of a cross-sectional study of 77 obese nondiabetic children (51% female; median age 11.7 years; BMI >97th percentile) enrolled at the University of Bonn, Bonn, Germany...
September 12, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28881695/correlation-of-hamp-gene-polymorphisms-and-expression-with-the-susceptibility-and-length-of-hospital-stays-in-taiwanese-children-with-kawasaki-disease
#6
Ying-Hsien Huang, Kuender D Yang, Yu-Wen Hsu, Hsing-Fang Lu, Henry Sung-Ching Wong, Hong-Ren Yu, Hsing-Chun Kuo, Fu-Chen Huang, Mao-Hung Lo, Kai-Sheng Hsieh, Su-Fen Chen, Wei-Chiao Chang, Ho-Chang Kuo
Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28840787/altering-plant-defenses-hamps-and-effector-arsenal-of-chewing-herbivores
#7
Saumik Basu, Suresh Varsani, Joe Louis
Chewing herbivores, such as caterpillars and beetles, while feeding on the host plant cause extensive tissue damage and release a wide array of cues to alter plant defenses. Consequently, the cues can have both beneficial and detrimental impacts on the chewing herbivores. Herbivore-Associated Molecular Patterns (HAMPs) are molecules produced by herbivorous insects that aids them to elicit plant defenses leading to impairment of insect growth, while effectors suppress plant defenses and contribute to increased susceptibility to subsequent feeding by chewing herbivores...
August 25, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28840425/hfe-mrna-expression-is-responsive-to-intracellular-and-extracellular-iron-loading-short-communication
#8
Kosha J Mehta, Sebastien Farnaud, Vinood B Patel
In liver hepatocytes, the HFE gene regulates cellular and systemic iron homeostasis by modulating cellular iron-uptake and producing the iron-hormone hepcidin in response to systemic iron elevation. However, the mechanism of iron-sensing in hepatocytes remain enigmatic. Therefore, to study the effect of iron on HFE and hepcidin (HAMP) expressions under distinct extracellular and intracellular iron-loading, we examined the effect of holotransferrin treatment (1, 2, 5 and 8 g/L for 6 h) on intracellular iron levels, and mRNA expressions of HFE and HAMP in wild-type HepG2 and previously characterized iron-loaded recombinant-TfR1 HepG2 cells...
August 24, 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28793778/peroxiredoxin-2-a-novel-regulator-of-iron-homeostasis-in-ineffective-erythropoiesis
#9
Alessandro Matte, Luigia De Falco, Enrica Federti, Anna Cozzi, Achille Iolascon, Sonia Levi, Narla Mohandas, Alberto Zamo, Mariasole Bruno, Christophe Leboeuf, Anne Janin, Angela Siciliano, Thomas Ganz, Giorgia Federico, Francesca Carlomagno, Sebastian Mueller, Ines Silva, Carmine Carbone, Davide Melisi, D W Kim, Soo Young Choi, Lucia DE Franceschi
AIMS: Iron-overload (IO) is a life-threatening complication of chronic hemolytic disorders such as β-thalassemia. IO results in severe cellular oxidative damage, leading to organ failure. Peroxiredoxin-2 (Prx2), a typical 2-cysteine-(Cys)-peroxiredoxin, is an important component of cyto-protective system, but its response to IO is still to be fully defined. RESULTS: We studied the effects of IO on Prx2-knockout mice (Prx2-/-). The absence of Prx2 enhanced toxicity due to IO on erythropoiesis...
August 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28780227/insights-into-the-immune-manipulation-mechanisms-of-pollen-allergens-by-protein-domain-profiling
#10
Seema Patel, Aruna Rani, Arun Goyal
Plant pollens are airborne allergens, as their inhalation causes immune activation, leading to rhinitis, conjunctivitis, sinusitis and oral allergy syndrome. A myriad of pollen proteins belonging to profilin, expansin, polygalacturonase, glucan endoglucosidase, pectin esterase, and lipid transfer protein class have been identified. In the present in silico study, the protein domains of fifteen pollen sequences were extracted from the UniProt database and submitted to the interactive web tool SMART (Simple Modular Architecture Research Tool), for finding the protein domain profiles...
July 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28768181/long-term-cold-adaptation-does-not-require-fgf21-or-ucp1
#11
Susanne Keipert, Maria Kutschke, Mario Ost, Thomas Schwarzmayr, Evert M van Schothorst, Daniel Lamp, Laura Brachthäuser, Isabel Hamp, Sithandiwe E Mazibuko, Sonja Hartwig, Stefan Lehr, Elisabeth Graf, Oliver Plettenburg, Frauke Neff, Matthias H Tschöp, Martin Jastroch
Brown adipose tissue (BAT)-dependent thermogenesis and its suggested augmenting hormone, FGF21, are potential therapeutic targets in current obesity and diabetes research. Here, we studied the role of UCP1 and FGF21 for metabolic homeostasis in the cold and dissected underlying molecular mechanisms using UCP1-FGF21 double-knockout mice. We report that neither UCP1 nor FGF21, nor even compensatory increases of FGF21 serum levels in UCP1 knockout mice, are required for defense of body temperature or for maintenance of energy metabolism and body weight...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28741998/retention-of-virulence-following-colistin-adaptation-in-klebsiella-pneumoniae-is-strain-dependent-rather-than-associated-with-specific-mutations
#12
Matthew E Wand, Lucy J Bock, J Mark Sutton
This study aimed to understand the impact on virulence and fitness of mutations in specific genes found after adaptation of Klebsiella pneumoniae to colistin. Isolates with an increase in their inhibitory concentration (MIC) to colistin of 32- to >128-fold were shown to have mutations in mgrB, phoPQ and pmrAB, all known regulators of pathways affecting membrane lipid content. When these strains were used in studies in Galleria mellonella there was no clear correlation between mutations in specific genes per se and loss of virulence...
July 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28735778/yoga-for-military-veterans-with-chronic-low-back-pain-a-randomized-clinical-trial
#13
Erik J Groessl, Lin Liu, Douglas G Chang, Julie L Wetherell, Jill E Bormann, J Hamp Atkinson, Sunita Baxi, Laura Schmalzl
INTRODUCTION: Chronic low back pain (cLBP) is prevalent, especially among military veterans. Many cLBP treatment options have limited benefits and are accompanied by side effects. Major efforts to reduce opioid use and embrace nonpharmacological pain treatments have resulted. Research with community cLBP patients indicates that yoga can improve health outcomes and has few side effects. The benefits of yoga among military veterans were examined. DESIGN: Participants were randomized to either yoga or delayed yoga treatment in 2013-2015...
July 17, 2017: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/28714907/genetic-contribution-to-alcohol-dependence-investigation-of-a-heterogeneous-german-sample-of-individuals-with-alcohol-dependence-chronic-alcoholic-pancreatitis-and-alcohol-related-cirrhosis
#14
Jens Treutlein, Josef Frank, Fabian Streit, Céline S Reinbold, Dilafruz Juraeva, Franziska Degenhardt, Liz Rietschel, Stephanie H Witt, Andreas J Forstner, Monika Ridinger, Jana Strohmaier, Norbert Wodarz, Helene Dukal, Jerome C Foo, Per Hoffmann, Stefan Herms, Stefanie Heilmann-Heimbach, Michael Soyka, Wolfgang Maier, Wolfgang Gaebel, Norbert Dahmen, Norbert Scherbaum, Bertram Müller-Myhsok, Susanne Lucae, Marcus Ising, Felix Stickel, Thomas Berg, Ulla Roggenbuck, Karl-Heinz Jöckel, Henrike Scholz, Ulrich S Zimmermann, Stephan Buch, Wolfgang H Sommer, Rainer Spanagel, Benedikt Brors, Sven Cichon, Karl Mann, Falk Kiefer, Jochen Hampe, Jonas Rosendahl, Markus M Nöthen, Marcella Rietschel
The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10(-6); pcorrected = 0.020). This was driven by the AD subsample...
July 17, 2017: Genes
https://www.readbyqxmd.com/read/28709862/1st-european-congress-of-medical-physics-september-1-4-2016-medical-physics-innovation-and-vision-within-europe-and-beyond
#15
EDITORIAL
Virginia Tsapaki, George C Kagadis, Marco Brambilla, Mario Ciocca, Catharine H Clark, Harry Delis, Giovanni Mettivier
Medical Physics is the scientific healthcare profession concerned with the application of the concepts and methods of physics in medicine. The European Federation of Organisations for Medical Physics (EFOMP) acts as the umbrella organization for European Medical Physics societies. Due to the rapid advancements in related scientific fields, medical physicists must have continuous education through workshops, training courses, conferences, and congresses during their professional life. The latest developments related to this increasingly significant medical speciality were presented during the 1st European Congress of Medical Physics 2016, held in Athens, September 1-4, 2016, organized by EFOMP, hosted by the Hellenic Association of Medical Physicists (HAMP), and summarized in the current volume...
July 11, 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28689299/4-o-methylhonokiol-protects-from-alcohol-carbon-tetrachloride-induced-liver-injury-in-mice
#16
Eleonora Patsenker, Andrea Chicca, Vanessa Petrucci, Sheida Moghadamrad, Andrea de Gottardi, Jochen Hampe, Jürg Gertsch, Nasser Semmo, Felix Stickel
Alcoholic liver disease (ALD) is a leading cause of liver cirrhosis, liver cancer, and related mortality. The endocannabinoid system contributes to the development of chronic liver diseases, where cannabinoid receptor 2 (CB2) has been shown to have a protecting role. Thus, here, we investigated how CB2 agonism by 4'-O-methylhonokiol (MHK), a biphenyl from Magnolia grandiflora, affects chronic alcohol-induced liver fibrosis and damage in mice. A combination of alcohol (10% vol/vol) and CCl4 (1 ml/kg) was applied to C57BL/6 mice for 5 weeks...
July 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28678075/patients-undergoing-orthotopic-liver-transplantation-require-lower-concentrations-of-the-volatile-anesthetic-sevoflurane
#17
Joanna Baron-Stefaniak, Viola Götz, Andreas Allhutter, Judith Schiefer, Thomas Hamp, Peter Faybik, Gabriela Berlakovich, David M Baron, Walter Plöchl
BACKGROUND: Sevoflurane is a volatile anesthetic commonly used to maintain anesthesia in patients with end-stage liver disease (ESLD) undergoing orthotopic liver transplantation (OLT). Growing evidence suggests that patients with ESLD have decreased anesthetic requirements compared to patients with preserved liver function. The potency of volatile anesthetics is expressed as the minimum alveolar concentration (MAC). In this prospective, blinded study, we compared the MAC of sevoflurane among patients with ESLD undergoing OLT and patients with normal liver function undergoing major abdominal surgery...
September 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28673786/diurnal-variations-in-iron-concentrations-and-expression-of-genes-involved-in-iron-absorption-and-metabolism-in-pigs
#18
Yiming Zhang, Dan Wan, Xihong Zhou, Ciming Long, Xin Wu, Lan Li, Liuqin He, Pan Huang, Shuai Chen, Bie Tan, Yulong Yin
Diurnal variations in serum iron levels have been well documented in clinical studies, and serum iron is an important diagnostic index for iron-deficiency anemia. However, the underlying mechanism of dynamic iron regulation in response to the circadian rhythm is still unclear. In this study, we investigated daily variations in iron status in the plasma and liver of pigs. The transcripts encoding key factors involved in iron uptake and homeostasis were evaluated. The results showed that iron levels in the plasma and liver exhibited diurnal rhythms...
September 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28649438/translational-learning-from-clinical-studies-predicts-drug-pharmacokinetics-across-patient-populations
#19
Markus Krauss, Ute Hofmann, Clemens Schafmayer, Svitlana Igel, Jan Schlender, Christian Mueller, Mario Brosch, Witigo von Schoenfels, Wiebke Erhart, Andreas Schuppert, Michael Block, Elke Schaeffeler, Gabriele Boehmer, Linus Goerlitz, Jan Hoecker, Joerg Lippert, Reinhold Kerb, Jochen Hampe, Lars Kuepfer, Matthias Schwab
Early indication of late-stage failure of novel candidate drugs could be facilitated by continuous integration, assessment, and transfer of knowledge acquired along pharmaceutical development programs. We here present a translational systems pharmacology workflow that combines drug cocktail probing in a specifically designed clinical study, physiologically based pharmacokinetic modeling, and Bayesian statistics to identify and transfer (patho-)physiological and drug-specific knowledge across distinct patient populations...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28648331/il-35-as-a-newly-proposed-homeostasis-associated-molecular-pattern-plays-three-major-functions-including-anti-inflammatory-initiator-effector-and-blocker-in-cardiovascular-diseases
#20
Xinyuan Li, Pu Fang, William Y Yang, Hong Wang, Xiaofeng Yang
IL-35 is a new anti-inflammatory cytokine identified in 2007, which inhibits inflammation and immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. The unique initiator and effector anti-inflammatory properties of IL-35 bring tremendous interest in investigating its role during cardiovascular disease (CVD) development, in which inflammatory processes are firmly established as central to its development and complications. In this review, we update recent understanding of how IL-35 is produced and regulated in the cells...
June 22, 2017: Cytokine
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