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Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N Uversky, Chul Geun Kim
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis...
March 14, 2018: Nucleic Acids Research
Ruchita Dixit, Sowmya Nettem, Simerjit S Madan, Htoo Htoo Kyaw Soe, Adinegara Bl Abas, Leah D Vance, Patrick J Stover
BACKGROUND: Sickle cell disease (SCD) is a group of disorders that affects haemoglobin, which causes distorted sickle- or crescent-shaped red blood cells. It is characterized by anaemia, increased susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with SCD, it is hypothesized that they are at an increased risk for folate deficiency...
March 16, 2018: Cochrane Database of Systematic Reviews
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
Carole Therasse, Isabelle Fusier, Anne-Laure Cordonnier, Florence Bérard, Olivier Parent de Curzon, François Bocquet, Pascal Paubel
AIM: Erythropoiesis-stimulating agents (ESAs) are particularly used to treat dialysis patients suffering from anemia due to renal failure. Since March 2014, ESAs have no longer been funded on top-of-diagnosis-related groups (DRGs) in French hospitals and are funded via DRGs. There are two ways to fund dialysis in French hospitals: the 'DRG for dialysis in session' and the 'off-dialysis DRG', which is not a DRG and consists in a supplement tariff specific to dialysis for patients hospitalized for another main reason than dialysis...
March 14, 2018: Journal of Comparative Effectiveness Research
Roxanne Labranche, Guillaume Gilbert, Milena Cerny, Kim-Nhien Vu, Denis Soulières, Damien Olivié, Jean-Sébastien Billiard, Takeshi Yokoo, An Tang
Iron overload is a systemic disorder and is either primary (genetic) or secondary (exogenous iron administration). Primary iron overload is most commonly associated with hereditary hemochromatosis and secondary iron overload with ineffective erythropoiesis (predominantly caused by β-thalassemia major and sickle cell disease) that requires long-term transfusion therapy, leading to transfusional hemosiderosis. Iron overload may lead to liver cirrhosis and hepatocellular carcinoma, in addition to cardiac and endocrine complications...
March 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Thijs Thomas Jansz, Akin Özyilmaz, Muriel P C Grooteman, Tiny Hoekstra, Marieke Romijn, Peter J Blankestijn, Michael L Bots, Brigit C van Jaarsveld
OBJECTIVES: Nocturnal haemodialysis (NHD), characterised by 8-hour sessions ≥3 times a week, is known to improve clinical parameters in the short term compared with conventional-schedule haemodialysis (HD), generally 3×3.5-4 hours a week. We studied long-term effects of NHD and used patients on conventional HD/haemodiafiltration (HDF) as controls. DESIGN: Four-year prospective follow-up of patients who switched to NHD; we compared patients with patients on HD/HDF using propensity score matching...
March 8, 2018: BMJ Open
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
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
Sabrina Giampaolo, Gabriela Wójcik, Stefan Klein-Hessling, Edgar Serfling, Amiya K Patra
The role of NFAT family transcription factors in erythropoiesis is so far unknown, although their involvement has been suggested previously. We have shown recently that Il2 -/- mice develop severe anemia due to defects in KLF1 activity during BM erythropoiesis. Although, KLF1 activity is indispensable for erythropoiesis, the molecular details of Klf1 expression have not yet been elucidated. Here we show that an enhanced NFATc1 activity induced by increased integrin-cAMP signaling plays a critical role in the dysregulation of Klf1 expression and thereby cause anemia in Il2 -/- mice...
February 9, 2018: Oncotarget
Neha Thakre, Priyanka Fernandes, Ann-Kristin Mueller, Frederik Graw
The blood-stage of the Plasmodium parasite is one of the key phases within its life cycle that influences disease progression during a malaria infection. The efficiency of the parasite in infecting red blood cells (RBC) determines parasite load and parasite-induced hemolysis that is responsible for the development of anemia and potentially drives severe disease progression. However, the molecular factors defining the infectivity of Plasmodium parasites have not been completely identified so far. Using the Plasmodium berghei mouse model for malaria, we characterized and compared the blood-stage infection dynamics of Pb ANKA WT and a mutant parasite strain lacking a novel Plasmodium antigen, Pb maLS_05, that is well conserved in both human and animal Plasmodium parasite strains...
2018: Frontiers in Microbiology
Hitesh H Shah, Steven Fishbane
Anemia is a common complication of advanced chronic kidney disease (CKD). Treatment with erythropoiesis-stimulating agents (ESAs) remains a common approach in managing anemia of CKD. The 2012 Kidney Disease Improving Global Outcomes Clinical Practice Guideline for Anemia in CKD suggests avoiding ESA therapy use to maintain Hb level above 11.5 g/dL. However, optimal Hb target range in adult patients undergoing chronic dialysis remains unknown. Clinical studies suggest risks associated with normalization of Hb levels in adult patients with CKD...
March 6, 2018: Seminars in Dialysis
J Lévy, D Haye, N Marziliano, G Casu, F Guimiot, C Dupont, N Teissier, B Benzacken, P Gressens, E Pipiras, A Verloes, A-C Tabet
Ephrin B2, one of the ligand of the EphB receptors, is involved in a complex signaling pathway regulating the development of the nervous system, neuronal migration, erythropoiesis and vasculogenesis. We report a patient with a de novo variant in EFNB2 and a family in which segregates a 610-kb deletion at chromosome 13q33 encompassing only ARGLU1 and EFNB2 genes. The de novo variant was observed in a patient with anal stenosis, hypoplastic left ventricle and mild developmental delay. The deletion was identified in 2 sibs with congenital heart defect and mild developmental delay...
March 6, 2018: Clinical Genetics
L Martin, N Zouhiri, M Audran, A Marchand
New therapeutic proteins that trap circulating members of the TGF beta superfamily (activins and growth differentiation factors) show promising effects on erythropoiesis and muscular growth. They are dimeric recombinant fusion proteins composed of the extracellular domain of a human activin receptor (ActRIIA or IIB) linked to the Fc part of human IgG1. Sotatercept (ActRIIA-Fc) and Luspatercept (a modified ActRIIB-Fc) in particular are now in phase 2/3 of clinical trials against anemia and included in the prohibited list established by the World Anti-Doping Agency...
March 2, 2018: Drug Testing and Analysis
Paul J Schmidt, Kaifeng Liu, Gary Visner, Kevin Fitzgerald, Shannon Fishman, Tim Racie, Julia L Hettinger, James S Butler, Mark D Fleming
Diminished β-globin synthesis in β-thalassemia is associated with ineffective erythropoiesis, leading to secondary iron overload caused by inappropriately low levels of hepcidin and to splenomegaly in the symptomatic thalassemias. Splenectomy is often employed in patients with β-thalassemia in order to reduce hemolysis. Expression of the iron regulatory peptide hormone hepcidin is repressed by the serine protease TMPRSS6. Hepcidin induction by RNAi-mediated inhibition of TMPRSS6 expression reduces iron overload and mitigates anemia in murine models of β-thalassemia intermedia...
March 2, 2018: American Journal of Hematology
Benoit Stijlemans, Patrick De Baetselier, Stefan Magez, Jo A Van Ginderachter, Carl De Trez
African trypanosomosis (AT) is a chronically debilitating parasitic disease of medical and economic importance for the development of sub-Saharan Africa. The trypanosomes that cause this disease are extracellular protozoan parasites that have developed efficient immune escape mechanisms to manipulate the entire host immune response to allow parasite survival and transmission. During the early stage of infection, a profound pro-inflammatory type 1 activation of the mononuclear phagocyte system (MPS), involving classically activated macrophages (i...
2018: Frontiers in Immunology
Hartmut Beck, Mario Jeske, Kai Thede, Friederike Stoll, Ingo Flamme, Metin Akbaba, Jens-Kerim Ergüden, Gunter Karig, Jörg Keldenich, Felix Oehme, Hans-Christian Militzer, Ingo V Hartung, Uwe Thuss
Small molecule inhibitors of hypoxia inducible factor prolyl hydroxylases (HIF-PHs) are currently under clinical development as novel treatment option for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased EPO expression and subsequently increased erythropoiesis. Herein we describe the discovery, synthesis, SAR and proposed binding mode of novel 2,4-diheteroaryl-1,2-dihydro-3H-pyrazol-3-ones as orally bioavailable HIF-PH inhibitors for the treatment of anemia...
February 27, 2018: ChemMedChem
Leonidas Benetatos, George Vartholomatos
DNA methylation (CpG methylation) exerts an important role in normal differentiation and proliferation of hematopoietic stem cells and their differentiated progeny, while it has also the ability to regulate myeloid versus lymphoid fate. Mutations of the epigenetic machinery are observed in hematological malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) resulting in hyper- or hypo-methylation affecting several different pathways. Enhancers are cis-regulatory elements which promote transcription activation and are characterized by histone marks including H3K27ac and H3K4me1/2...
February 26, 2018: Cellular and Molecular Life Sciences: CMLS
Lulu Liu, Xiaoling Wan, Peipei Zhou, Xiaoyuan Zhou, Wei Zhang, Xinhui Hui, Xiujie Yuan, Xiaodan Ding, Ruihong Zhu, Guangxun Meng, Hui Xiao, Feng Ma, He Huang, Xianmin Song, Bin Zhou, Sidong Xiong, Yan Zhang
BACKGROUND: Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis...
February 26, 2018: Journal of Hematology & Oncology
Rafiou Agoro, Anna Montagna, Regina Goetz, Onyedikachi Aligbe, Gurinder Singh, Lindsay M Coe, Moosa Mohammadi, Stefano Rivella, Despina Sitara
Severe anemia and iron deficiency are common complications in chronic kidney disease. The cause of renal anemia is multifactorial and includes decreased erythropoietin (Epo) production, iron deficiency, and inflammation, and it is currently treated with injections of synthetic Epo. However, the use of recombinant Epo has several adverse effects. We previously reported that high fibroblast growth factor 23 (FGF23) levels in mice are associated with decreased red blood cell production, whereas genetic inactivation of Fgf23 results in expansion of the erythroid lineage...
February 26, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
L Tauzin, V Campos, M Tichet
Reticulocytes and erythrocytes are the ultimate differentiated stages of erythropoiesis. In addition to being anucleate cells, they are characterized by the clearance of their mitochondrial pool or lack thereof. Given that for most research-oriented flow cytometry experiments erythrocytes and reticulocytes are often undesirable cell types, their identification and exclusion from analyses can be essential. Here, we describe a flow cytometric method based on cellular NAD(P)H-related autofluorescence, whose localization is mainly associated with mitochondria...
February 26, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
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