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Megakaryocyte

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https://www.readbyqxmd.com/read/28432529/ginseng-derived-panaxadiol-saponins-promote-hematopoiesis-recovery-in-cyclophosphamide-induced-myelosuppressive-mice-potential-novel-treatment-of-chemotherapy-induced-cytopenias
#1
Xin Sun, Yan-Na Zhao, Song Qian, Rui-Lan Gao, Li-Ming Yin, Li-Pei Wang, Beng-Hock Chong, Su-Zhan Zhang
OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX). METHODS: Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot...
April 22, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28432223/fli1-level-during-megakaryopoiesis-affects-thrombopoiesis-and-platelet-biology
#2
Karen K Vo, Danuta J Jarocha, Randolph B Lyde, Vincent Hayes, Christopher S Thom, Spencer K Sullivan, Deborah L French, Mortimer Poncz
Friend Leukemia Virus Integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is amongst genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a PTSx patient and iPSCs from a control line with a targeted heterozygous FLI1 knockout (FLI1(+/-))...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28430954/increased-multinucleated-megakaryocytes-as-an-isolated-finding-in-bone-marrow-%C3%A2-a-rare-finding-and-its-clinical-significance
#3
Majd D Jawad, Ronald S Go, Kaaren K Reichard, Min Shi
Objectives: Multinucleated megakaryocytes are a unique morphologic form of megakaryocytes characterized by multiple, distinctly separated nuclei. We investigated whether increased multinucleated megakaryocytes (≥25%) in otherwise normal-appearing bone marrow were associated with the development of a myelodysplastic syndrome (MDS). Methods: We retrospectively reviewed the medical records and bone marrow biopsy specimens of patients evaluated at our institution from 2011 to 2015 that met all of the following criteria: (1) 25% or more multinucleated megakaryocytes, (2) no other dysplastic features, (3) absence of a myeloid neoplasm, and (4) absence of neoplastic karyotypic abnormalities...
November 1, 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28428218/gain-of-function-mutation-in-filamin-a-potentiates-platelet-integrin-%C3%AE-iib%C3%AE-3-activation
#4
Eliane Berrou, Frédéric Adam, Marilyne Lebret, Virginie Planche, Patricia Fergelot, Odile Issertial, Isabelle Coupry, Jean-Claude Bordet, Paquita Nurden, Dominique Bonneau, Estelle Colin, Cyril Goizet, Jean-Philippe Rosa, Marijke Bryckaert
OBJECTIVE: Dominant mutations of the X-linked filamin A (FLNA) gene are responsible for filaminopathies A, which are rare disorders including brain periventricular nodular heterotopia, congenital intestinal pseudo-obstruction, cardiac valves or skeleton malformations, and often macrothrombocytopenia. APPROACH AND RESULTS: We studied a male patient with periventricular nodular heterotopia and congenital intestinal pseudo-obstruction, his unique X-linked FLNA allele carrying a stop codon mutation resulting in a 100-amino acid-long FLNa C-terminal extension (NP_001447...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28428120/pathogenesis-of-immune-thrombocytopenia
#5
REVIEW
Sylvain Audia, Matthieu Mahévas, Maxime Samson, Bertrand Godeau, Bernard Bonnotte
Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigen-presenting cell during ITP. CD8(+) T cells also participate to thrombocytopenia by increasing platelet apoptosis...
April 17, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28427432/anti-human-platelet-antigen-hpa-1a-antibodies-may-affect-trophoblast-functions-crucial-for-placental-development-a-laboratory-study-using-an-in-vitro-model
#6
Mariana Eksteen, Gøril Heide, Heidi Tiller, Yan Zhou, Nora Hersoug Nedberg, Inigo Martinez-Zubiaurre, Anne Husebekk, Bjørn R Skogen, Tor B Stuge, Mette Kjær
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies...
April 21, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28423484/mir-494-3p-overexpression-promotes-megakaryocytopoiesis-in-primary-myelofibrosis-hematopoietic-stem-progenitor-cells-by-targeting-socs6
#7
Sebastiano Rontauroli, Ruggiero Norfo, Valentina Pennucci, Roberta Zini, Samantha Ruberti, Elisa Bianchi, Simona Salati, Zelia Prudente, Chiara Rossi, Vittorio Rosti, Paola Guglielmelli, Giovanni Barosi, Alessandro Vannucchi, Enrico Tagliafico, Rossella Manfredini
Primary myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by hematopoietic stem cell-derived clonal myeloproliferation, involving especially the megakaryocyte lineage. To better characterize how the altered expression of microRNAs might contribute to PMF pathogenesis, we have previously performed the integrative analysis of gene and microRNA expression profiles of PMF hematopoietic stem/progenitor cells (HSPCs), which allowed us to identify miR-494-3p as the upregulated microRNA predicted to target the highest number of downregulated mRNAs...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420865/a-novel-variant-t-1-22-translocation-ins-22-1-q13-p13p31-in-a-child-with-acute-megakaryoblastic-leukemia
#8
Elizabeth Margolskee, Jad Saab, Julia T Geyer, Alexander Aledo, Susan Mathew
BACKGROUND The reciprocal translocation t(1;22)(p13;q13) involving the RBM15 and MKL1 genes is an uncommon abnormality that occurs in a subset of acute myeloid leukemia with megakaryocytic differentiation (AMKL). Variant translocations have been infrequently described in this subtype of leukemia. CASE REPORT We describe the case of a 3-month-old girl who presented with progressive abdominal distension, vomiting, and fever. Although there was no morphologic evidence of leukemia in the bone marrow, cytogenetic and metaphase fluorescence in situ hybridization analysis identified an insertion of p13p31 bands of chromosome 1 onto the long arm of chromosome 22, resulting in the karyotype: 46,XX,ins(22;1)(q13;p13p31)...
April 19, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28416610/evidence-for-shear-mediated-ca-2-entry-through-mechanosensitive-cation-channels-in-human-platelets-and-a-megakaryocytic-cell-line
#9
Zeki Ilkan, Joy R Wright, Alison H Goodall, Jonathan M Gibbins, Chris I Jones, Martyn P Mahaut-Smith
The role of mechanosensitive (MS) Ca(2+)-permeable ion channels in platelets is unclear, despite the importance of shear stress in platelet function and life-threatening thrombus formation. We therefore sought to investigate the expression and functional relevance of MS channels in human platelets. The effect of shear stress on Ca(2+) entry in human platelets and Meg-01 megakaryocytic cells loaded with Fluo-3 was examined by confocal microscopy. Cells were attached to microscope slides within flow chambers that allowed applications of physiological and pathological shear stress...
April 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28416505/hematopoietic-transcription-factors-mutations-important-players-in-inherited-platelet-defects
#10
Natthapol Songdej, A Koneti Rao
Transcription factors (TF) are proteins that bind to specific DNA sequences and regulate expression of genes. The molecular and genetic mechanisms in most patients with inherited platelet defects are unknown. There is now increasing evidence that mutations in hematopoietic TFs are an important underlying cause for defects in platelet production, morphology, and function. The hematopoietic TFs implicated in patients with impaired platelet function and number include runt related transcription factor 1 (RUNX1), Fli-1 proto-oncogene, ETS transcription factor (FLI1), GATA-binding protein 1 (GATA1), growth factor independent 1B transcriptional repressor (GFI1B), ETS variant 6 (ETV6), ecotropic viral integration site 1 (EVI1), and homeobox A11 (HOXA11)...
April 17, 2017: Blood
https://www.readbyqxmd.com/read/28412372/flavonoids-and-platelet-aggregation-a-brief-review
#11
REVIEW
Caterina Faggio, Antoni Sureda, Silvia Morabito, Ana Sanches Silva, Andrei Mocan, Seyed Fazel Nabavi, Seyed Mohammad Nabavi
Platelets are small anucleated fragments derived from a megakaryocyte precursor. Platelets play a key role in many physiological functions especially in hemostasis and wound healing processes in order to maintain the integrity of the circulatory system. In addition, activated platelets release cytokines and chemokines which modulate the immune response and, in some cases of hyperactivation, they could be associated to the pathogenesis of inflammatory diseases. Flavonoids are polyphenolic compounds ubiquosly found in plants known to be potent antioxidants with positive effects against diverse diseases such as cancer, neurodegenerative or cardiovascular disease...
April 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28411253/a-new-path-to-platelet-production-through-matrix-sensing
#12
Vittorio Abbonante, Christian Andrea Di Buduo, Cristian Gruppi, Carmelo De Maria, Elise Spedden, Aurora De Acutis, Cristian Staii, Mario Raspanti, Giovanni Vozzi, David Kaplan, Francesco Moccia, Katya Ravid, Alessandra Balduini
Megakaryocytes in the bone marrow are immersed in a network of extracellular matrix (ECM) components that regulate platelet release into the circulation. Combining biological and bioengineering approaches, we found that the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechano-sensitive ion channel, is induced upon megakaryocyte adhesion on softer matrices. This response promoted platelet production by triggering a cascade of events that lead to calcium influx, β1 integrin activation and internalization, and Akt phosphorylation, responses not found on stiffer matrices...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28410150/platelet-toll-like-receptors-in-thromboinflammation
#13
Lina Paola D' Atri, Mirta Schattner
Besides their undiscussed role in hemostasis and thrombosis, platelets are also key effector cells capable of assisting and modulating inflammatory reactions and immune responses. Platelets play a sentinel role in immune surveillance by recognizing danger signals from pathogens and cell damage through the expression of toll-like receptors (TLRs) on its surface and internal compartments. Platelets express all 10 TLRs transcripts and its signalosome, including adaptor proteins and transcription factors. The activation of these receptors in platelets triggers hemostatic and inflammatory responses which participate in the host's response to bacterial and viral infections, linking thrombosis with infection and immunity...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28405618/efficacy-of-alk5-inhibition-in-myelofibrosis
#14
Lanzhu Yue, Matthias Bartenstein, Wanke Zhao, Wanting Tina Ho, Ying Han, Cem Murdun, Adam W Mailloux, Ling Zhang, Xuefeng Wang, Anjali Budhathoki, Kith Pradhan, Franck Rapaport, Huaquan Wang, Zonghong Shao, Xiubao Ren, Ulrich Steidl, Ross L Levine, Zhizhuang Joe Zhao, Amit Verma, Pearlie K Epling-Burnette
Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28404913/a-novel-role-of-ckip-1-in-promoting-megakaryocytic-differentiation
#15
Jiao Fan, Yiwu Wang, Yuan Shen, Qingyan Liu, Rong Gao, Ya Qiu, Chanjuan Wang, Lingqiang Zhang
Casein kinase 2-interacting protein-1 (CKIP-1) is a known regulator of cardiomyocytes and macrophage proliferation. In this study, we showed that CKIP-1 was involved in the process of megakaryocytic differentiation. During megakaryocytic differentiation of K562 cells, CKIP-1 was dramatically upregulated and this upregulation induced by PMA was mediated through downregulation of transcription factor GATA-1. By transient transfection, oligonucleotide-directed mutagenesis and chromatin immunoprecipitation assays, we identified the transcriptional regulation of CKIP-1 by GATA-1...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402443/effect-of-radiation-induced-endothelial-cell-injury-on-platelet-regeneration-by-megakaryocytes
#16
Fang Chen, Mingqiang Shen, Dongfeng Zeng, Cheng Wang, Song Wang, Shilei Chen, Yong Tang, Mengjia Hu, Mo Chen, Yongping Su, Xinze Ran, Yang Xu, Junping Wang
Thrombocytopenia is an important cause of hemorrhage and death after radiation injury, but the pathogenesis of radiation-induced thrombocytopenia has not been fully characterized. Here, we investigated the influence of radiation-induced endothelial cell injury on platelet regeneration. We found that human umbilical vein endothelial cells (HUVECs) underwent a high rate of apoptosis, accompanied by a significant reduction in the expression of vascular endothelial growth factor (VEGF) at 96 h after radiation. Subsequent investigations revealed that radiation injury lowered the ability of HUVECs to attract migrating megakaryocytes (MKs)...
April 11, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28401061/transcription-factor-gfi1b-in-health-and-disease
#17
REVIEW
Eduardo Anguita, Francisco J Candel, Alberto Chaparro, Juan J Roldán-Etcheverry
Many human diseases arise through dysregulation of genes that control key cell fate pathways. Transcription factors (TFs) are major cell fate regulators frequently involved in cancer, particularly in leukemia. The GFI1B gene, coding a TF, was identified by sequence homology with the oncogene growth factor independence 1 (GFI1). Both GFI1 and GFI1B have six C-terminal C2H2 zinc fingers and an N-terminal SNAG (SNAIL/GFI1) transcriptional repression domain. Gfi1 is essential for neutrophil differentiation in mice...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28391511/normal-and-pathological-dynamics-of-platelets-in-humans
#18
Gabriel P Langlois, Morgan Craig, Antony R Humphries, Michael C Mackey, Joseph M Mahaffy, Jacques Bélair, Thibault Moulin, Sean R Sinclair, Liangliang Wang
We develop a mathematical model of platelet, megakaryocyte, and thrombopoietin dynamics in humans. We show that there is a single stationary solution that can undergo a Hopf bifurcation, and use this information to investigate both normal and pathological platelet production, specifically cyclic thrombocytopenia. Carefully estimating model parameters from laboratory and clinical data, we then argue that a subset of parameters are involved in the genesis of cyclic thrombocytopenia based on clinical information...
April 8, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28391186/dual-channel-active-contour-model-for-megakaryocytic-cell-segmentation-in-bone-marrow-trephine-histology-images
#19
Tzu-Hsi Song, Victor Sanchez, Hesham ElDaly, Nasir Rajpoot
Assessment of morphological features of megakaryocytes (special kind of cells) in bone marrow trephine biopsies play an important role in the classification of different subtypes of Philadelphia-chromosome-negative myeloproliferative neoplasms (Ph-negative MPNs). In order to aid hematopathologists in the study of megakaryocytes, we propose a novel framework that can efficiently delineate the nuclei and cytoplasm of these cells in digitized images of bone marrow trephine biopsies. The framework first employs a supervised machine learning approach that utilizes color and texture features to delineate megakaryocytic nuclei...
April 4, 2017: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/28388313/arachidonic-acid-and-docosahexanoic-acid-enhance-platelet-formation-from-human-apheresis-derived-cd34-cells
#20
Ankita Dhenge, Kedar Limbkar, Sameer Melinkeri, Vaijayanti Prakash Kale, Lalita Limaye
An Aberration in megakaryopoiesis and thrombopoiesis, 2 important processes that maintain hemostasis, leads to thrombocytopenia. Though platelet transfusions are used to treat this condition, blood banks frequently face a shortage of platelets. Therefore, methods to generate platelets on a large scale are strongly desirable. However, to generate megakaryocytes (MKs) and platelets (PLTs) in numbers sufficient for clinical application, it is essential to understand the mechanism of platelet production and explore efficient strategies accordingly...
April 7, 2017: Cell Cycle
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