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Dirk Fahrenkamp, Jinyu Li, Sabrina Ernst, Hildegard Schmitz-Van de Leur, Nicolas Chatain, Andrea Küster, Steffen Koschmieder, Bernhard Lüscher, Giulia Rossetti, Gerhard Müller-Newen
STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins...
October 18, 2016: Scientific Reports
Guang-Fu Chen, Hui-Tao Li, Jin-Jie Huang, Zhang-Xing Wang, Yun Li, Chuan-Zhong Yang, Ben-Qing Wu, Wen-Lan Liu, Li-Hui Liu, Qi Kong, Rong-Tian Liu
OBJECTIVE: To study the relationship between the levels of erythropoietin (EPO) in serum and brain injury in preterm infants. METHODS: Three hundred and four preterm infants (gestational age: 28-34 weeks) born between October 2014 and September 2015 were enrolled in this study. Brain injury was diagnosed using cerebral ultrasound and MRI. The levels of EPO, S100 protein, neuron-specific enolase (NSE) and myelin basic protein (MBP) in serum were detected using ELISA...
October 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Michael J Feldman, Saman Sizdahkhani, Nancy A Edwards, Marsha J Merrill, Abhik Ray-Chaudhury, Zhengping Zhuang, Russell R Lonser, Edward H Oldfield, Prashant Chittiboina
von Hippel-Lindau (VHL) patients develop multiple central nervous system hemangioblastomas (HB). Some HBs become symptomatic with exponential growth or cyst formation following long periods of quiescence. Understanding the factors underlying growth in hemangioblastoma may lead to better strategies to arrest or prevent tumor growth. In 5 VHL patients, we resected quiescent hemangioblastomas (Q-HB) that were en-route during surgical access to symptomatic hemangioblastomas (S-HB), for matched tumor analysis. Quantitative reverse transcriptase analysis demonstrated a 2-fold increase in EPO expression in all S-HB, while 4/5 showed either Hypoxia Inducible Factor-1α or 2α upregulation...
October 17, 2016: Scientific Reports
Anna Ngo, Ann Koay, Christian Pecquet, Carmen C Diaconu, Yasmine Ould-Amer, Qiwei Huang, Congbao Kang, Anders Poulsen, May Ann Lee, David Jenkins, Andrew Shiau, Stefan N Constantinescu, Meng Ling Choo
BACKGROUND: Rather than a Janus Kinase 2 inhibitor (ruxolitinib), a specific thrombopoietin receptor (TpoR) inhibitor would be more specific for the treatment of myeloproliferative neoplasms due to TpoR mutations. OBJECTIVE: A cell-based phenotypic approach to identify specific TpoR inhibitors was implemented and a library of 505,483 small molecules was screened for inhibitory effects on cells transformed by TpoR mutants. RESULTS: Among the identified hits are two analogs of 3-(4-piperidinyl) indole...
October 10, 2016: Combinatorial Chemistry & High Throughput Screening
Daniel Gruneberg, Felipe A Montellano, Konstanze Plaschke, Lexiao Li, Hugo H Marti, Reiner Kunze
Episodes of cerebral hypoxia/ischemia increase the risk of dementia, which is associated with impaired learning and memory. Previous studies in rodent models of dementia indicated a favorable effect of the hypoxia-inducible factor (HIF) targets VEGF (vascular endothelial growth factor) and erythropoietin (Epo). In the present study we thus investigated whether activation of the entire adaptive HIF pathway in neurons by cell-specific deletion of the HIF suppressor prolyl-4-hydroxylase 2 (PHD2) improves cognitive abilities in young (3months) and old (18-28months) mice suffering from chronic brain hypoperfusion...
October 5, 2016: Experimental Neurology
Qing Ren, Xing-Fang Zhang, Jin-Ying Yang
OBJECTIVE: The aim of the study was to investigate whether erythropoietin (EPO) could protect against white matter damage (WMD) in a preterm equivalent neonatal rat hypoxic-ischemia (HI) model. METHODS: 113 two-day-old male rat pups were divided randomly into three groups: sham-treated, bilateral carotid artery occlusion (BCAO)-treated, BCAO + EPO-treated group. EPO (50 U/10 g body weight) or saline alone was administered intraperitoneally immediately after BCAO surgery...
October 8, 2016: Neurological Research
Gaurav Agarwal, Padam Hirachan, Jonathan Gelfond, Paolo Fanti, Claudia Hura, Shweta Bansal
BACKGROUND: Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency (VDD) is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effect of oral ergocalciferol supplementation on requirement of erythropoietin (EPO) and active vitamin D analogues, and hospitalization rate in maintenance hemodialysis (HD) patients. METHODS: This retrospective cohort study included 186 patients who were on HD for 3 months and had 25(OH)D levels < 30 ng/ml...
October 7, 2016: BMC Nephrology
Masato Okano, Mitsuhiko Sato, Shinji Kageyama
Human erythropoietin (EPO) and recombinant human EPO (rEPO) are approximately 30-kDa glycosylated proteins comprising 165 amino acids. Darbepoetin alfa (NESP) is a glycosylated protein encompassing five changes in the amino acid sequence of human EPO, which contains two extra sugar chains. NESP is under patent protection in the USA until May 2024 and in Europe until July 2016, which suggests that the number of NESP biosimilars might substantially increase. The detailed characterization of biosimilar products are required to ensure the identity and purity of the biosimilar products in terms of safety and efficacy for patients...
October 5, 2016: Drug Testing and Analysis
Ruixing Liu, Yanling Wang, Mingliang Pu, Jie Gao
PURPOSE: This study was conducted to determine whether alpha lipoic acid (ALA) promotes the survival of retinal ganglion cells (RGCs) in a rat model of optic nerve crush (ONC) injury and to investigate the neuroprotective mechanisms of ALA in the retina in this ONC injury model. METHODS: Adult male Sprague-Dawley rats (180-220 g) were subjected to ONC injury surgery. ALA (63 mg/kg) was injected intravenously 1 day before or after the ONC injury. Animals were euthanized after 10 days, and the number of ganglion cells positive for RNA-binding protein with multiple splicing (Rbpms), which is an RGC marker, were counted on the whole mount retinas...
2016: Molecular Vision
Yan Zhao, Yuan Zuo, Jianming Jiang, Huibo Yan, Xiliang Wang, Hunjun Huo, Yulong Xiao
Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group)...
October 2016: Experimental and Therapeutic Medicine
Caroline Bengtsson, Eva Lindberg, Lars Jonsson, Mats Holmström, Fredrik Sundbom, Jan Hedner, Andrei Malinovschi, Roelinde Middelveld, Bertil Forsberg, Christer Janson
STUDY OBJECTIVES: To analyse the prevalence of sleep problems in subjects with CRS and to determine whether the disease severity of CRS affects sleep quality. METHODS: Questionnaires were sent to a random sample of 45 000 adults in four Swedish cities. Questions on CRS, asthma, allergic rhinitis, co-morbidities, tobacco use, educational level and physical activity were included. CRS was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) epidemiological criteria...
September 26, 2016: Sleep
Evanthia Pangou, Christina Befani, Ilias Mylonis, Martina Samiotaki, George Panayotou, George Simos, Panagiotis Liakos
Hypoxia Inducible Factor 2 (HIF-2) is a transcriptional activator implicated in the cellular response to hypoxia. Regulation of its inducible subunit, HIF-2α, involves post-translational modifications. Here, we demonstrate that casein kinase 1δ (CK1δ) phosphorylates HIF-2α at Ser383 and Thr528 in vitro Disruption of these phosphorylation sites and silencing or chemical inhibition of CK1δ reduced the expression of HIF-2 target genes and the secretion of erythropoietin (EPO) in two hepatic cancer cell lines, Huh7 and HepG2, without affecting levels of HIF-2α protein expression...
September 29, 2016: Journal of Cell Science
Shucheng Gu, Yanjun Xv, Chengming Fei, Chao Xiao, Juan Guo, Youshan Zhao, Feng Xv, Xiao Li, Chunkang Chang
OBJECTIVES: In order to gain an insight into labile plasma iron (LPI) in iron metabolism microenvironment in MDS. METHODS: We performed ELISA, quantitative real-time polymerase chain reaction, flow cytometry, MRI T2* assays to test LPI, iron biochemical parameters, and liver iron concentration (LIC) among 22 MDS patients. RESULTS: LPI has a statistical difference (P < 0.001 by analysis of variance (ANOVA)), which decreased gradually, among three groups, while no difference was found in adjusted serum ferritin (ASF) (P = 0...
August 11, 2016: Hematology (Amsterdam, Netherlands)
Andres A Urrutia, Aqeela Afzal, Jacob Nelson, Olena Davidoff, Kenneth W Gross, Volker H Haase
A classic response to systemic hypoxia is the increased production of red blood cells due to hypoxia-inducible factor (HIF)-mediated induction of erythropoietin (EPO). EPO is a glycoprotein hormone that is essential for normal erythropoiesis and is predominantly synthesized by peritubular renal interstitial fibroblast-like cells, which express cellular markers characteristic of neuronal cells and pericytes. To investigate whether the ability to synthesize EPO is a general functional feature of pericytes, we used conditional gene targeting to examine the von Hippel-Lindau (VHL) / prolyl-4-hydroxylase domain (PHD) / HIF axis in cell expressing neural glial antigen 2 (NG2), a known molecular marker of pericytes in multiple organs...
September 28, 2016: Blood
Wen-Hung Huang, Ching-Wei Hsu, Cheng-Hao Weng, Dan-Tzu Lin-Tan, Tzung-Hai Yen
The adverse effects of increased blood lead levels have been well discussed. Several antioxidant agents have been reported to offer protection from lead toxicity and to reduce blood lead levels (BLL). Given that erythropoietin (EPO) also has antioxidant properties, the aim of this cross-sectional study was to assess the role of EPO and other clinical variables on BLL in hemodialysis (HD) patients. We recruited 931 maintenance hemodialysis (MHD) patients who had undergone HD for at least 6 months and who had ever received blood lead level (BLL) study...
September 29, 2016: Scientific Reports
Mlc Tanchoco, A S Aguilar
No abstract text is available yet for this article.
November 2015: Journal of Minimally Invasive Gynecology
Hao Lu, Xiaoyue Wu, Zejing Wang, Li Li, Wen Chen, Mingcan Yang, Da Huo, Wen Zeng, Chuhong Zhu
BACKGROUND: Mesenchymal stem cell (MSC) transplantation is an effective treatment therapy for ischemic ulcers. However, in high-glucose microenvironment, the original inflammation-inhibiting function of MSCs leads to turns into secreting large amounts of inflammatory mediators, such as tumor necrosis factor alpha, for example, which decreases their capacity and becomes poor quality stem cells over inflammation cells for diabetic foot ulcers repair in the healing of diabetic foot ulcers...
October 2016: Journal of Surgical Research
Yamila Rodríguez Cruz, Manon Strehaiano, Teresita Rodríguez Obaya, Julío César García Rodríguez, Tangui Maurice
Erythropoietin (EPO) is a cytokine known to have effective cytoprotective action in the brain, particularly in ischemic, traumatic, inflammatory, and neurodegenerative conditions. We previously reported the neuroprotective effect of a low sialic form of EPO, Neuro-EPO, applied intranasally in rodent models of stroke or cerebellar ataxia and in a non-transgenic mouse model of Alzheimer's disease (AD). Here we analyzed the protective effect of Neuro-EPO in APPSwe mice, a reference transgenic mouse model of AD...
September 20, 2016: Journal of Alzheimer's Disease: JAD
Fangfang Yan, Chao Jiang, Yan Meng, Huijuan Li, Lie Yu, Xiaojie Fu, Youcai Tang, Meimei Zhang
Erythropoietin (EPO) is important for angiogenesis after hypoxia/ischemia. In this study, we investigated whether recombinant human erythropoietin (rhEPO) can enhance angiogenesis, and promote cognitive function through vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway in a rat model of hypoxic-ischemic encephalopathy (HIE). RhEPO, selective VEGFR2 inhibitor (SU5416) or vehicle was administrated by intraperitoneal injection. The assessment for cognitive function begins on day 60 after anoxia...
September 19, 2016: Brain Research
Adrienne M Laury, Sarah N Bowe, Joshua Stramiello, Kevin C McMains
OBJECTIVES/HYPOTHESIS: To determine the primary diagnoses for which balloon catheter dilation (BCD) of sinus ostia is being employed in a profit-blind health care system, the Department of Defense. STUDY DESIGN: Retrospective chart review. METHODS: From January 1, 2011 to December 31, 2013, 319 consecutive patient charts were reviewed for International Classification of Diseases, Ninth Edition (ICD-9) diagnoses, presence of chronic rhinosinusitis (CRS) defined by the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), preoperative Lund-Mackay scores, nasal endoscopy findings, sinuses dilated, postoperative outcomes, and complications...
September 23, 2016: Laryngoscope
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