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Erythropoietin

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https://www.readbyqxmd.com/read/28449418/hif-prolyl-hydroxylases-as-therapeutic-targets-in-erythropoiesis-and-iron-metabolism
#1
REVIEW
Volker H Haase
A classic response to systemic hypoxia is the increase in red blood cell production. This response is controlled by the prolyl hydroxylase domain/hypoxia-inducible factor (HIF) pathway, which regulates a broad spectrum of cellular functions. The discovery of this pathway as a key regulator of erythropoiesis has led to the development of small molecules that stimulate the production of endogenous erythropoietin and enhance iron metabolism. This review provides a concise overview of the cellular and molecular mechanisms that govern HIF-induced erythropoietic responses and provides an update on clinical experience with compounds that target HIF-prolyl hydroxylases for anemia therapy...
June 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28448184/erythropoietin-mediates-brain-vascular-kidney-crosstalk-and-may-be-a-treatment-target-for-pulmonary-and-resistant-essential-hypertension
#2
Emine Meltem Onal, Alan Alper Sag, Oguzhan Sal, Aslihan Yerlikaya, Baris Afsar, Mehmet Kanbay
Organ crosstalk pathways represent the next frontier for target-mining in molecular medicine for existing syndromes. Pulmonary hypertension and resistant essential hypertension are syndromes that have been proven elusive in etiology, and frequently refractory to first-line management. Underlying crosstalk mechanisms, not yet considered in these treatments, may hinder outcomes or unlock novel treatments. This review focuses systematically on erythropoietin, a synthesizable molecule, as a mediator of brain-kidney crosstalk...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28447859/transgene-expression-in-dogs-after-liver-directed-hydrodynamic-delivery-of-i-sleeping-beauty-i-transposons-using-balloon-catheters
#3
Kendra Anne Hyland, Elena L Aronovich, Erik R Olson, Jason B Bell, Myra Urness Rusten, Roland Gunther, David W Hunter, Perry B Hackett, R Scott McIvor
The <i>Sleeping Beauty</i> transposon system has been extensively tested for integration of reporter and therapeutic genes <i>in vitro</i> and <i>in vivo</i> in mice. Dogs were used as a large animal model for human therapy and minimally invasive infusion of DNA solutions. DNA solutions were delivered into the entire liver or the left side of the liver using balloon catheters for temporary occlusion of venous outflow. A peak intravascular pressure between 80 and 140 mmHg supported sufficient DNA delivery in dog liver for detection of secretable reporter proteins...
April 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28446734/iron-deficiency-and-anemia-in-heart-failure
#4
Yüksel Çavuşoğlu, Hakan Altay, Mustafa Çetiner, Tolga Sinan Güvenç, Ahmet Temizhan, Dilek Ural, Dilek Yeşilbursa, Nesligül Yıldırım, Mehmet Birhan Yılmaz
Heart failure is an important community health problem. Prevalence and incidence of heart failure have continued to rise over the years. Despite recent advances in heart failure therapy, prognosis is still poor, rehospitalization rate is very high, and quality of life is worse. Co-morbidities in heart failure have negative impact on clinical course of the disease, further impair prognosis, and add difficulties to treatment of clinical picture. Therefore, successful management of co-morbidities is strongly recommended in addition to conventional therapy for heart failure...
March 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28446125/soluble-transferrin-receptor-as-a-marker-of-erythropoiesis-in-patients-undergoing-high-flux-hemodialysis
#5
Pei Yin, Jijun Li, Yan Song
Anemia is a common complication in chronic kidney disease (CKD) patients receiving hemodialysis. The effect of high-flux dialysis (HFD) on anemia remains unclear. This prospective study aimed to evaluate the effect of HFD on anemia, and the potential of soluble transferrin receptor (sTfR) as a marker of iron status and erythropoiesis in CKD patients on hemodialysis. Forty patients, who switched from conventional low-flux dialysis to HFD for 12 months, were enrolled in this study. The levels of sTfR, hemoglobin, iron, and nutritional markers, as well as the dose of recombinant human erythropoietin (rhEPO) and use of chalybeate were determined at 0, 2, 6, and 12 months after starting HFD...
April 27, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28445874/erythropoietin-treatment-exacerbates-moderate-injury-after-hypoxia-ischemia-in-neonatal-superoxide-dismutase-transgenic-mice
#6
R Ann Sheldon, Christine Windsor, Byong Sop Lee, Olatz Arteaga Cabeza, Donna M Ferriero
The neonatal brain is highly susceptible to oxidative stress as developing endogenous antioxidant mechanisms are overwhelmed. In the neonate, superoxide dismutase (SOD) overexpression worsens hypoxic-ischemic injury due to H2O2 accumulation in the brain. Erythropoietin (EPO) is upregulated in 2 phases after HI, early (4 h) and late (7 days), and exogenous EPO has been effective in reducing the injury, possibly through reducing oxidative stress. We hypothesized that exogenous EPO would limit injury from excess H2O2 seen in SOD1-overexpressing mice, and thus enhance recovery after HI...
April 27, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28441110/effects-of-the-us-food-and-drug-administration-boxed-warning-of-erythropoietin-stimulating-agents-on-utilization-and-adverse-outcome
#7
John Bian, Brian Chen, Dawn L Hershman, Norman Marks, LeAnn Norris, Richard Schulz, Charles Bennett
Purpose In March 2007, a US Food and Drug Administration boxed warning was issued for erythropoietin-stimulating agents (ESAs) regarding serious adverse events, such as venous thromboembolism (VTE). We evaluated the US Food and Drug Administration's boxed warning of ESAs used to treat chemotherapy-induced anemia because evidence on the effectiveness of boxed warnings remains inconclusive. Patients and Methods Using 2004 to 2009 SEER-Medicare data, we exploited a natural experiment to examine the effects of ESA boxed warnings on utilization and risk of VTE...
April 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28438754/smad1-5-is-required-for-erythropoietin-mediated-suppression-of-hepcidin-in-mice
#8
Chia-Yu Wang, Amanda B Core, Susanna Canali, Kimberly B Zumbrennen-Bullough, Sinan Ozer, Lieve Umans, An Zwijsen, Jodie L Babitt
Anemia suppresses liver hepcidin expression to supply adequate iron for erythropoiesis. Erythroferrone mediates hepcidin suppression by anemia, but its mechanism of action remains uncertain. The bone morphogenetic protein (BMP)-SMAD signaling pathway has a central role in hepcidin transcriptional regulation. Here, we explored the contribution of individual receptor-activated SMADs in hepcidin regulation and their involvement in erythroferrone suppression of hepcidin. In Hep3B cells, SMAD5 or SMAD1, but not SMAD8, knockdown inhibited hepcidin (HAMP) mRNA expression...
April 24, 2017: Blood
https://www.readbyqxmd.com/read/28435991/polycythemia-capillary-rarefaction-and-focal-glomerulosclerosis-in-two-adolescents-born-extremely-low-birth-weight-and-premature
#9
Nariaki Asada, Takanori Tsukahara, Megumi Furuhata, Daisuke Matsuoka, Shunsuke Noda, Kuniaki Naganuma, Akinori Hashiguchi, Midori Awazu
BACKGROUND: Low birthweight infants have a reduced number of nephrons and are at high risk of chronic kidney disease. Preterm birth and/or intrauterine growth restriction (IUGR) may also affect peritubular capillary development, as has been shown in other organs. CASE-DIAGNOSIS/TREATMENT: We report two patients with a history of preterm birth and extremely low birthweight who showed polycythemia and renal capillary rarefaction. Patient 1 and 2, born at 25 weeks of gestation with a birthweight of 728 and 466 g, showed mild proteinuria at age 8 and 6 years, respectively...
April 24, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28433798/randomized-trial-of-early-erythropoietin-supplementation-after-preterm-birth-iron-metabolism-and-outcome
#10
O M Peltoniemi, E Anttila, T Kaukola, G Buonocore, M Hallman
BACKGROUND: Excess of iron and oxidant injury shortly after birth may be associated with neonatal morbidities in preterm infants. AIMS: The aim was to determine whether administration of erythropoietin without iron supplementation decreases iron load and morbidity. STUDY DESIGN AND SUBJECTS: In a randomized trial, we administered erythropoietin (EPO 250IU/kg daily during the first 6days of life) or placebo to 39 preterm infants (BW 700-1500g, GA≤30...
April 20, 2017: Early Human Development
https://www.readbyqxmd.com/read/28433433/design-selection-and-development-of-cyclic-peptide-ligands-for-human-erythropoietin
#11
William S Kish, Hiroyuki Sachi, Amith D Naik, Matthew K Roach, Benjamin G Bobay, Robert K Blackburn, Stefano Menegatti, Ruben G Carbonell
This work presents the selection and characterization of erythropoietin (EPO)-binding cyclic peptide ligands. The sequences were selected by screening a focused library of cyclic depsipeptides cyclo[(Nα-Ac)Dap(A)-X1-X6-AE], whose structure and amino acid compositions were tailored to mimic the EPO receptor. The sequences identified through library screening were synthesized on chromatographic resin and characterized via binding-and-elution studies against EPO to select a pool of candidate ligands. Sequences with higher hydrophobicity consistently showed stronger binding to EPO, with the exception of FSLLSH, which was noted for its lower hydrophobicity and high EPO binding...
April 12, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28426392/design-and-validation-of-a-new-method-to-detect-and-quantify-residual-host-cell-dna-in-human-recombinant-erythropoietin-repo
#12
Shima Zamanian, Samira Mohammadi-Yeganeh, Vahid Kia, Hooman Kaghazian, Mahdi Paryan
During the purification of Human Recombinant EPO (rEPO) from host cells, residual DNA may remain in final products. This contamination is a risk factor for patients and may result in the inactivation of some tumor suppressor genes (TSG) or activation of oncogenes if its concentration is more than the standard defined by WHO. Based on WHO's criteria, acceptable level of residual DNA in biopharmaceuticals is less than 10-100 picograms/dose. In this study we have designed a sensitive and specific Quantitative Real-time PCR assay for detection of residual DNA in human rEPO products...
April 20, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/28423937/concordance-of-several-subcellular-interactions-initiates-alzheimer-s-dementia-their-reversal-requires-combination-treatment
#13
W J Fessel
The pathogenesis of Alzheimer's disease involves multiple pathways that, at the macrolevel, include decreased proliferation plus increased loss affecting neurons, astrocytes, and capillaries and, at the subcellular level, involve several elements: amyloid/amyloid precursor protein, presenilins, the unfolded protein response, the ubiquitin/proteasome system, the Wnt/catenin system, the Notch signaling system, mitochondria, mitophagy, calcium, and tau. Data presented show the intimate, anatomical interactions between neurons, astrocytes, and capillaries; the interactions between the several subcellular factors affecting those cells; and the treatments that are currently available and that might correct dysfunctions in the subcellular factors...
May 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28423608/anthracyclines-suppress-pheochromocytoma-cell-characteristics-including-metastasis-through-inhibition-of-the-hypoxia-signaling-pathway
#14
Ying Pang, Chunzhang Yang, Jan Schovanek, Herui Wang, Petra Bullova, Veronika Caisova, Garima Gupta, Katherine I Wolf, Gregg L Semenza, Zhengping Zhuang, Karel Pacak
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423311/physiological-plasticity-of-neural-crest-derived-stem-cells-in-the-adult-mammalian-carotid-body
#15
Valentina Annese, Elena Navarro-Guerrero, Ismael Rodríguez-Prieto, Ricardo Pardal
Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28421649/decreased-expression-of-epha5-is-associated-with-fuhrman-nuclear-grade-and-pathological-tumour-stage-in-ccrcc
#16
Xiaolin Wang, Haifei Xu, Zhijun Wu, Xiao Chen, Jiandong Wang
The incidence of renal cell carcinoma is increasing all over the world. The molecular mechanisms for tumorigenesis, progression and prognosis are still unknown. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors have been reported to be expressed aberrantly in many types of human cancers and in particular EphA5 may play a role in certain human cancers. In this study, a set of clear cell renal cell carcinoma (ccRCC) tissues were subjected to immunohistochemistry. The relationship between EphA5 protein expression and clinicopathological parameters was statistically analysed...
April 19, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28419985/erythropoietin-derived-peptide-protects-against-acute-lung-injury-after-rat-traumatic-brain-injury
#17
Yuan Liu, Junyu Lu, Xiaoya Wang, Liu Chen, Su Liu, Zhiren Zhang, Wei Yao
BACKGROUND: Traumatic brain injury (TBI) can be complicated by TBI-triggered acute lung injury (ALI), in which inflammation plays a central role. It has been reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate TBI; however, its function in TBI-caused ALI has not been reported yet. METHODS: In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight-drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and eosin (H&E) staining of lung sections was carried out...
April 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28419696/risk-factors-associated-with-pain-on-chronic-intermittent-hemodialysis-a-systematic-review
#18
REVIEW
Tonci Brkovic, Eliana Burilovic, Livia Puljak
OBJECTIVES: The aim of the study was to define risk factors related to pain in adult end-stage renal disease (ESRD) patients on chronic intermittent hemodialysis (HD) by developing a systematic review of published data. METHODS: The search was conducted from MEDLINE, Scopus, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). Manuscripts in all languages were considered. Two authors performed each step independently, and all disagreements were resolved after discussion with the third author...
April 18, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28418910/erythropoietin-drives-breast-cancer-progression-by-activation-of-its-receptor-epor
#19
Ka Kui Chan, Kyle B Matchett, Jonathan A Coulter, Hiu-Fung Yuen, Cian M McCrudden, Shu-Dong Zhang, Gareth W Irwin, Matthew A Davidson, Thomas Rülicke, Sophie Schober, Ludger Hengst, Heidelinde Jaekel, Angela Platt-Higgins, Philip S Rudland, Ken I Mills, Perry Maxwell, Mohamed El-Tanani, Terence R Lappin
Breast cancer is a leading cause of cancer-related deaths. Anemia is common in breast cancer patients and can be treated with blood transfusions or with recombinant erythropoietin (EPO) to stimulate red blood cell production. Clinical studies have indicated decreased survival in some groups of cancer patients treated with EPO. Numerous tumor cells express the EPO receptor (EPOR), posing a risk that EPO treatment would enhance tumor growth, but the mechanisms involved in breast tumor progression are poorly understood...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417130/iron-isotopic-composition-of-blood-serum-in-anemia-of-chronic-kidney-disease
#20
Yulia Anoshkina, Marta Costas-Rodríguez, Marijn Speeckaert, Wim Van Biesen, Joris Delanghe, Frank Vanhaecke
Chronic kidney disease (CKD) is a general term for disorders that affect the structure and function of the kidneys. Iron deficiency (ID) and anemia occur in the vast majority of CKD patients, most of whom are elderly. However, establishing the cause of anemia in CKD, and therefore making an informed decision concerning the corresponding therapeutic treatment, is still a challenge. High-precision Fe isotopic analysis of blood serum samples of CKD patients with and without ID/anemia was performed via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose...
April 18, 2017: Metallomics: Integrated Biometal Science
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