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Giulia Ravasi, Sara Pelucchi, Gaia Buoli Comani, Federico Greni, Raffaella Mariani, Irene Pelloni, Silvia Bombelli, Roberto Perego, Donatella Barisani, Alberto Piperno
OBJECTIVE: During hypoxia hepcidin expression is inhibited to allow iron mobilization to sustain erythropoietic expansion. We analysed molecular mechanisms underlying hypoxia-induced hepcidin inhibition in an in vivo model of acute hypoxia. METHODS: Mice were kept under normal or hypoxic conditions for 6h and 15h and treated with α-PDGF-BB antibody or PDGF-BB receptor inhibitor. Blood, liver, spleen, and bone marrow were collected to extract RNA and protein or to quantify EPO and PDGF-BB...
March 15, 2018: European Journal of Haematology
Charles K Davis, Sreekala S Nampoothiri, G K Rajanikant
The constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential to PHD2, FIH, and pVHL was further verified by re-docking, molecular dynamics (MD) simulation and by Drug Affinity Responsive Target Stability (DARTS) assay...
March 14, 2018: Molecular Neurobiology
Tochukwu C Okwuosa, Cindy Soares, Verena Golwitzer, Rober Habashy, Peter Timmins, Mohamed A Alhnan
A method for the production of liquid capsules with the potential of modifying drug dose and release is presented. For the first time, the co-ordinated use of fused deposition modelling (FDM), 3D printing and liquid dispensing to fabricate individualised dosage form on demand in a fully automated fashion has been demonstrated. Polymethacrylate shells (Eudragit EPO and RL) for immediate and extended release were fabricated using FDM 3D printing and simultaneously filled using a computer-controlled liquid dispenser loaded with model drug solution (theophylline) or suspension (dipyridamole)...
March 11, 2018: European Journal of Pharmaceutical Sciences
Nariaki Asada
Kidneys are physiologically hypoxic due to huge oxygen consumption for tubular reabsorption. The physiological hypoxia makes the kidney an appropriate organ for sensitively detecting oxygen levels and producing erythropoietin (EPO). In preterm neonates, immature kidneys cannot produce sufficient EPO, which results in anemia of prematurity (AOP). The cause of EPO insufficiency in AOP has been unclear, therefore current therapeutic options are transfusion and injection of recombinant human EPO. This report shows that the cause of insufficient EPO production in AOP is elevated renal oxygen levels due to poor oxygen consumption by immature tubules...
March 13, 2018: Scientific Reports
Ying Pang, Garima Gupta, Chunzhang Yang, Herui Wang, Thanh-Truc Huynh, Ziedulla Abdullaev, Svetlana D Pack, Melanie J Percy, Terence R J Lappin, Zhengping Zhuang, Karel Pacak
BACKGROUND: The role of the hypoxia signaling pathway in the pathogenesis of pheochromocytoma/paraganglioma (PPGL)-polycythemia syndrome has been elucidated. Novel somatic mutations in hypoxia-inducible factor type 2A (HIF2A) and germline mutations in prolyl hydroxylase type 1 and type 2 (PHD1 and PHD2) have been identified to cause upregulation of the hypoxia signaling pathway and its target genes including erythropoietin (EPO) and its receptor (EPOR). However, in a minority of patients presenting with this syndrome, the genetics and molecular pathogenesis remain unexplained...
March 13, 2018: BMC Cancer
Chenlang Liu, Fangnan Yu, Qingshu Liu, Xiaoying Bian, Shengbiao Hu, Huansheng Yang, Yulong Yin, Yuezhong Li, Yuemao Shen, Liqiu Xia, Qiang Tu, Youming Zhang
Transporter engineering has been shown to be a positive approach for enhancing natural product titers in microbial cell factories by expelling target compounds out of feasible hosts. In this work, two multidrug efflux pumps, Orf14 and Orf3, were modulated in the epothilone production strain Burkholderia DSM7029::Tn5-km-epo (named G32) via Red/ET engineering to increase heterologous polyketide epothilone yields. Compared with the prior G32 strain, the total production of several epothilones in the G32::orf14-orf3 mutant was meaningfully doubled according to high-performance liquid chromatography-mass spectrometer (HPLC-MS) analysis...
February 26, 2018: FEMS Microbiology Letters
Yanjie Li, Clemens Altaner
Time and resource are the restricting factors for the wider use of chemical information of wood in tree breeding programs. NIR offers an advantage over wet-chemical analysis in these aspects and is starting to be used for tree breeding. This work describes the development of a NIR-based assessment of extractive content in heartwood of E. bosistoana, which does not require milling and conditioning of the samples. This was achieved by applying the signal processing algorithms (external parameter orthogonalisation (EPO) and significance multivariate correlation (sMC)) to spectra obtained from solid wood cores, which were able to correct for moisture content, grain direction and sample form...
March 1, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Katsuhiro Yamanaka, Mohamed Eldeiry, Muhammad Aftab, Joshua Mares, Thomas J Ryan, Xianzhong Meng, Michael J Weyant, Joseph C Cleveland, David A Fullerton, T Brett Reece
BACKGROUND: Paraplegia remains the most feared complication of complex thoracoabdominal aortic intervention. Although erythropoietin (EPO) has demonstrated neuroprotective effects in spinal cord ischemia, it does not work until expression of the beta common receptor subunit of the EPO receptor (βcR) is induced by ischemia. We hypothesized that the βcR can be induced by diazoxide (DZ), amplifying the neuroprotective effects of EPO in spinal cord ischemia-reperfusion injury. METHODS: For the DZ time trial, adult male C57/BL6 mice received DZ (20 mg/kg) by oral gavage...
February 9, 2018: Journal of Thoracic and Cardiovascular Surgery
Ting Hong, Zhijuan Ge, Ran Meng, Hongdong Wang, Pengzi Zhang, Sunyinyan Tang, Jing Lu, Tianwei Gu, Dalong Zhu, Yan Bi
Erythropoietin (EPO), besides its stimulatory effect on erythropoiesis, is beneficial to insulin resistance and obesity. However, its role in hepatic steatosis remains unexplored. Activating autophagy seems a promising mechanism for improving fatty liver disease. The present study investigated the role of EPO in alleviating hepatic steatosis and sought to determine whether its function is mediated by the activation of autophagy. Here, we show that EPO decreased hepatic lipid content significantly in vivo and in vitro...
March 6, 2018: Biochimica et Biophysica Acta
Wenxing Zhu, Lujiang Hao, Xinli Liu, Borrás-Hidalgo Orlando, Yuyu Zhang
Epothilones constitute a new class of microtubule-stabilizing anticancer agents with promising preclinical and clinical activity. However, its systemic application still causes some toxic side effects. To reduce these undesired effects, advanced drug delivery systems based on cell targeting carriers are needed currently. In this study, the high quality bacterial ghosts of the probiotic Escherichia coli Nissle 1917 (EcN) were prepared in a large scale and retained fully intact surface structures for specific attachment to mammalian cells...
March 9, 2018: Drug Development and Industrial Pharmacy
Dariusz Sitkowski, Zbigniew Szygula, Andrzej Pokrywka, Dariusz Turowski, Jadwiga Malczewska-Lenczowska
Interrelationships between physiological changes (Δ) in erythropoietin (EPO), plasma volume (PV), haemoglobin concentration ([Hb]), and total haemoglobin mass (tHb-mass) were examined in cyclists who trained in different altitudes. Regardless of differences in pattern of changes observed in three training locations, ΔEPO was correlated positively with ΔPV, negatively with Δ[Hb], and trivially with ΔtHb-mass. Δ[Hb] was negatively correlated with ΔPV. In the pooled data the Spearman's rank correlation coefficients were as follows: r = 0...
March 8, 2018: Research in Sports Medicine
Sandra E Juul, Bryan A Comstock, Patrick J Heagerty, Dennis E Mayock, Amy M Goodman, Stephanie Hauge, Fernando Gonzalez, Yvonne W Wu
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and frequently leads to significant long-term disability in survivors. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Adjunctive therapies are needed, and erythropoietin (Epo) has the potential to provide additional neuroprotection. OBJECTIVES: The aim of this study was to review the current incidence, mechanism of injury, and sequelae of HIE, and to describe a new phase III randomized, placebo-controlled trial of Epo neuroprotection in term and near-term infants with moderate to severe HIE treated with therapeutic hypothermia...
March 7, 2018: Neonatology
Frank Friedersdorff, Therese-Marie Koch, Beatriz Banuelos-Marco, Ricardo Gonzalez, Tom Florian Fuller, Stefanie von Mechow, Dominik Müller, Anja Lingnau
INTRODUCTION: To evaluate graft- and patient survival after paediatric kidney transplantation and detecting influence factors, which affect the post-transplant time. MATERIALS AND METHODS: We analysed long-term survival rates and complications after paediatric kidney transplantation and searched for predictive parameters for graft function. RESULTS: In 132 patients, 143 kidney transplantations were performed. Graft failure occurred in 25%...
March 7, 2018: Urologia Internationalis
Jakub Zmajkovic, Pontus Lundberg, Ronny Nienhold, Maria L Torgersen, Anders Sundan, Anders Waage, Radek C Skoda
Familial erythrocytosis with elevated erythropoietin levels is frequently caused by mutations in genes that regulate oxygen-dependent transcription of the gene encoding erythropoietin ( EPO). We identified a mutation in EPO that cosegregated with disease with a logarithm of the odds (LOD) score of 3.3 in a family with autosomal dominant erythrocytosis. This mutation, a single-nucleotide deletion (c.32delG), introduces a frameshift in exon 2 that interrupts translation of the main EPO messenger RNA (mRNA) transcript but initiates excess production of erythropoietin from what is normally a noncoding EPO mRNA transcribed from an alternative promoter located in intron 1...
March 8, 2018: New England Journal of Medicine
Friederike Grosse-Holz, Luisa Madeira, Muhammad Awais Zahid, Molly Songer, Jiorgos Kourelis, Mary Fesenko, Sabrina Ninck, Farnusch Kaschani, Markus Kaiser, Renier A L van der Hoorn
Agroinfiltrated Nicotiana benthamiana is a flexible and scalable platform for recombinant protein (RP) production, but its great potential is hampered by plant proteases that degrade RPs. Here, we tested 29 candidate protease inhibitors (PIs) in agroinfiltrated N. benthamiana leaves for enhancing accumulation of three unrelated RPs: glycoenzyme α-Galactosidase; glycohormone erythropoietin (EPO); and IgG antibody VRC01. Of the previously described PIs enhancing RP accumulation, we found only cystatin SlCYS8 to be effective...
March 6, 2018: Plant Biotechnology Journal
Charlotte Harrison
No abstract text is available yet for this article.
March 6, 2018: Nature Biotechnology
Niels J Aachmann-Andersen, Soren J Christensen, Kristian Lisbjerg, Peter Oturai, Pär I Johansson, Niels-Henrik Holstein-Rathlou, Niels V Olsen
The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance)...
March 2018: Physiological Reports
Michele F Eisenga, Lyanne M Kieneker, Daan J Touw, Ilja M Nolte, Peter van der Meer, Gerwin Huls, Carlo A J M Gaillard, Stephan J L Bakker
Cigarette smoking continues to be one of the major risk factors for increased morbidity and mortality worldwide. Among many adverse health effects, smoking can induce erythrocytosis, which is commonly believed to result from elevated serum erythropoietin (EPO) levels. Currently, however, this notion is only alleged, without data available to substantiate it. Hence, we analyzed data from the Prevention of Renal and Vascular End-Stage Disease study, a prospective population-based cohort study. Smoking behavior was quantified as number of cigarettes smoked per day and as 24-hour urinary cotinine excretion levels, an objective and quantitative measure of nicotine exposure...
March 2018: Mayo Clinic Proceedings
Jin Hyen Baek, Ayla Yalamanoglu, So-Eun Moon, Yamei Gao, Paul W Buehler
BACKGROUND: Red blood cell (RBC) oxygen (O2 ) delivery may be impacted at the tissue, cellular, and molecular levels after storage duration, preservation strategies, and pathogen reduction. Collectively, the preclinical measurement of arterial and venous PO2 , systemic blood flow, tissue hypoxia-inducible factors (HIFs), pimonidazole adduction, and erythropoietin (EPO) regulation can serve to elucidate differential RBC quality after storage and processing. STUDY DESIGN AND METHODS: Donor guinea pig blood was collected, leukoreduced, and stored at 4°C in AS-3 for 1 (fresh) or 14 (stored) days...
March 1, 2018: Transfusion
N K Singhal, K Alkhayer, J Shelestak, R Clements, E Freeman, J McDonough
Multiple sclerosis (MS) is a neuro-inflammatory and demyelinating disease. Downregulation of neuronal mitochondrial gene expression and activity have been reported in several studies of MS. We have previously shown that hemoglobin-β (Hbb) signals to the nucleus of neurons and upregulates H3K4me3, a histone mark involved in regulating cellular metabolism and differentiation. The present study was undertaken to evaluate the effect of erythropoietin (EPO) on the upregulation of hemoglobin and mitochondrial-associated neuroprotection...
March 1, 2018: Molecular Neurobiology
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