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https://www.readbyqxmd.com/read/28324272/lusutrombopag-increases-hematocytes-in-a-compensated-liver-cirrhosis-patient
#1
Akira Sakamaki, Takayuki Watanabe, Satoshi Abe, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai
A 56-year-old Japanese man with liver cirrhosis (LC) due to hepatitis C virus was admitted to our hospital for radiofrequency ablation of residual tumor following lusutrombopag administration. Laboratory tests revealed thrombocytopenia and leukopenia. The patient's LC was managed, and he was classified as Child-Pugh A. After admission, lusutrombopag was administered for 7 days. The platelet count increased to over 50,000/mm(3) after 7-14 days and returned to previous levels 50 days after administration. Leukocyte and erythrocyte counts also increased in response to the treatment and stayed elevated for over 120 days...
March 21, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28324211/comparison-of-in-vitro-osteogenic-potential-of-iliac-crest-and-degenerative-facet-joint-bone-autografts-for-intervertebral-fusion-in-lumbar-spinal-stenosis
#2
Jeroen Geurts, Daniela Ramp, Stefan Schären, Cordula Netzer
PURPOSE: The promotion of spinal fusion using bone autografts is largely mediated by the osteoinductive potential of progenitors/mesenchymal stem cells (MSC) that reside in the marrow spaces of cancellous bone. Iliac crest is the common autograft donor site, but its use presents an increased risk for donor site pain, morbidity and infection. Degenerative bone samples harvested during facetectomy might provide an alternative viable source of osteoinductive autografts. In this study, we conducted an intra-individual comparison of the osteogenic potential of isolated low passage MSC from both sources...
March 21, 2017: European Spine Journal
https://www.readbyqxmd.com/read/28324104/vasoprotective-activities-of-the-adrenomedullin-ramp2-system-in-endothelial-cells
#3
Xian Xian, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Megumu Tanaka, Teruhide Koyama, Hisaka Kawate, Lei Yang, Tian Liu, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Neointimal hyperplasia is the primary lesion underlying atherosclerosis and restenosis after coronary intervention. We previously described the essential angiogenic function of the adrenomedullin (AM)-receptor activity-modifying protein 2 (RAMP2) system. In the present study, we assessed the vasoprotective actions of the endogenous AM-RAMP2 system using a wire-induced vascular injury model. We found that neointima formation and vascular smooth muscle cell proliferation were enhanced in RAMP2+/- male mice. The injured vessels from RAMP2+/- mice showed greater macrophage infiltration, inflammatory cytokine expression and oxidative stress than vessels from wild-type mice, and less re-endothelialization...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323942/incretin-therapies-do-not-expand-%C3%AE-cell-mass-or-alter-pancreatic-histology-in-young-male-mice
#4
Aaron R Cox, Carol J Lam, Matthew M Rankin, Jacqueline S Rios, Julia Chavez, Claire W Bonnyman, Kourtney B King, Roger A Wells, Deepti Anthony, Justin X Tu, Jenny J Kim, Changhong Li, Jake A Kushner
The impact of incretins upon pancreatic β-cell expansion remains extremely controversial. Multiple studies indicate that incretin-based therapies can increase β-cell proliferation, and incretins have been hypothesized to expand β-cell mass. However, considerable disagreement exists on whether incretins actually increase β-cell mass. Moreover, some reports indicate that incretins may cause metaplastic changes in pancreatic histology. To resolve these questions we treated a large cohort of mice with incretin-based therapies and carried out a rigorous analysis of β-cell turnover and pancreatic histology using high-throughput imaging...
March 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323899/lawsonia-intracellularis-exploits-%C3%AE-catenin-wnt-and-notch-signalling-pathways-during-infection-of-intestinal-crypt-to-alter-cell-homeostasis-and-promote-cell-proliferation
#5
Yang W Huan, Rebecca J Bengtsson, Neil MacIntyre, Jack Guthrie, Heather Finlayson, Sionagh H Smith, Alan L Archibald, Tahar Ait-Ali
Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification...
2017: PloS One
https://www.readbyqxmd.com/read/28323876/pim1-minicircle-as-a-therapeutic-treatment-for-myocardial-infarction
#6
Nan Liu, Bingyan J Wang, Kathleen M Broughton, Roberto Alvarez, Sailay Siddiqi, Rebeca Loaiza, Nicky Nguyen, Pearl Quijada, Natalie Gude, Mark A Sussman
PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28323411/engineering-an-injectable-muscle-specific-microenvironment-for-improved-cell-delivery-using-a-nanofibrous-extracellular-matrix-hydrogel
#7
Nikhil Rao, Gillie Agmon, Matthew T Tierney, Jessica L Ungerleider, Rebecca L Braden, Alessandra Sacco, Karen L Christman
Injection of skeletal muscle progenitors has the potential to be a minimally invasive treatment for a number of diseases that negatively affect vasculature and skeletal muscle, including peripheral artery disease (PAD). However, success with this approach has been limited because of poor transplant cell survival. This is primarily attributed to cell death due to extensional flow through the needle, the harsh ischemic environment of the host tissue, a deleterious immune cell response, and a lack of biophysical cues supporting exogenous cell viability...
March 21, 2017: ACS Nano
https://www.readbyqxmd.com/read/28319735/different-combinations-of-growth-factors-for-the-tenogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-in-monolayer-culture-and-in-fibrin-based-three-dimensional-constructs
#8
Marta Bottagisio, Silvia Lopa, Valentina Granata, Giuseppe Talò, Chiara Bazzocchi, Matteo Moretti, Arianna Barbara Lovati
Tendon injuries are severe burdens in clinics. The poor tendon healing is related to an ineffective response of resident cells and inadequate vascularization. Thanks to the high proliferation and multi-lineage differentiation capability, bone marrow-derived mesenchymal stem cells (BMSCs) are a promising cell source to support the tendon repair. To date, the association of various growth factors to induce the in vitro tenogenic differentiation of multipotent progenitor cells is poorly investigated. This study aimed to investigate the tenogenic differentiation of rabbit BMSCs by testing the combination of bone morphogenetic proteins (BMP-12 and 14) with transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) both in 2D and 3D cultures within fibrin-based constructs...
March 16, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28319168/targeting-chronic-cardiac-remodeling-with-cardiac-progenitor-cells-in-a-murine-model-of-ischemia-reperfusion-injury
#9
Janine C Deddens, Dries A Feyen, Peter-Paul Zwetsloot, Maike A Brans, Sailay Siddiqi, Linda W van Laake, Pieter A Doevendans, Joost P Sluijter
BACKGROUND: Translational failure for cardiovascular disease is a substantial problem involving both high research costs and an ongoing lack of novel treatment modalities. Despite the progress already made, cell therapy for chronic heart failure in the clinical setting is still hampered by poor translation. We used a murine model of chronic ischemia/reperfusion injury to examine the effect of minimally invasive application of cardiac progenitor cells (CPC) in cardiac remodeling and to improve clinical translation...
2017: PloS One
https://www.readbyqxmd.com/read/28319094/targeting-c-fos-and-dusp1-abrogates-intrinsic-resistance-to-tyrosine-kinase-inhibitor-therapy-in-bcr-abl-induced-leukemia
#10
Meenu Kesarwani, Zachary Kincaid, Ahmed Gomaa, Erika Huber, Sara Rohrabaugh, Zain Siddiqui, Muhammad F Bouso, Tahir Latif, Ming Xu, Kakajan Komurov, James C Mulloy, Jose A Cancelas, H Leighton Grimes, Mohammad Azam
Tyrosine-kinase inhibitor (TKI) therapy for human cancers is not curative, and relapse occurs owing to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD stem or progenitor cells in the absence of oncogenic kinase signaling, a phenomenon referred to as intrinsic resistance, depends on diverse growth factors. Here we report that oncogenic kinase and growth-factor signaling converge to induce the expression of the signaling proteins FBJ osteosarcoma oncogene (c-FOS, encoded by Fos) and dual-specificity phosphatase 1 (DUSP1)...
March 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28319093/human-haematopoietic-stem-cell-lineage-commitment-is-a-continuous-process
#11
Lars Velten, Simon F Haas, Simon Raffel, Sandra Blaszkiewicz, Saiful Islam, Bianca P Hennig, Christoph Hirche, Christoph Lutz, Eike C Buss, Daniel Nowak, Tobias Boch, Wolf-Karsten Hofmann, Anthony D Ho, Wolfgang Huber, Andreas Trumpp, Marieke A G Essers, Lars M Steinmetz
Blood formation is believed to occur through stepwise progression of haematopoietic stem cells (HSCs) following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on the analysis of predefined flow-sorted cell populations. Here we integrated flow cytometric, transcriptomic and functional data at single-cell resolution to quantitatively map early differentiation of human HSCs towards lineage commitment. During homeostasis, individual HSCs gradually acquire lineage biases along multiple directions without passing through discrete hierarchically organized progenitor populations...
March 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28319048/amino-acid-insensitive-mtorc1-regulation-enables-nutritional-stress-resilience-in-hematopoietic-stem-cells
#12
Demetrios Kalaitzidis, Dongjun Lee, Alejo Efeyan, Youmna Kfoury, Naema Nayyar, David B Sykes, Francois E Mercier, Ani Papazian, Ninib Baryawno, Gabriel D Victora, Donna Neuberg, David M Sabatini, David T Scadden
The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity. Here, we have evaluated differential nutrient-sensing dependence through RagA and mTORC1 in hematopoietic progenitors, which dynamically drive mature cell production, and hematopoietic stem cells (HSC), which provide a quiescent cellular reserve...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318761/the-bone-marrow-microenvironment-home-of-the-leukemic-blasts
#13
REVIEW
Manar S Shafat, Bruno Gnaneswaran, Kristian M Bowles, Stuart A Rushworth
Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML...
March 12, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28318485/shaping-the-sound-of-voice
#14
Ralph Marcucio
The proper development of the vocal cords requires embryos to contain a certain number of progenitor cells, and mutations that lead to an overflow of cells can cause malformations of the voice box.
March 20, 2017: ELife
https://www.readbyqxmd.com/read/28318017/thymic-crosstalk-restrains-the-pool-of-cortical-thymic-epithelial-cells-with-progenitor-properties
#15
Catarina Meireles, Ana R Ribeiro, Rute D Pinto, Catarina Leitão, Pedro M Rodrigues, Nuno L Alves
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs)...
March 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28317875/chd7-is-indispensable-for-mammalian-brain-development-through-activation-of-a-neuronal-differentiation-programme
#16
Weijun Feng, Daisuke Kawauchi, Huiqin Körkel-Qu, Huan Deng, Elisabeth Serger, Laura Sieber, Jenna Ariel Lieberman, Silvia Jimeno-González, Sander Lambo, Bola S Hanna, Yassin Harim, Malin Jansen, Anna Neuerburg, Olga Friesen, Marc Zuckermann, Vijayanad Rajendran, Jan Gronych, Olivier Ayrault, Andrey Korshunov, David T W Jones, Marcel Kool, Paul A Northcott, Peter Lichter, Felipe Cortés-Ledesma, Stefan M Pfister, Hai-Kun Liu
Mutations in chromatin modifier genes are frequently associated with neurodevelopmental diseases. We herein demonstrate that the chromodomain helicase DNA-binding protein 7 (Chd7), frequently associated with CHARGE syndrome, is indispensable for normal cerebellar development. Genetic inactivation of Chd7 in cerebellar granule neuron progenitors leads to cerebellar hypoplasia in mice, due to the impairment of granule neuron differentiation, induction of apoptosis and abnormal localization of Purkinje cells, which closely recapitulates known clinical features in the cerebella of CHARGE patients...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28317842/bde-99-impairs-differentiation-of-human-and-mouse-npcs-into-the-oligodendroglial-lineage-by-species-specific-modes-of-action
#17
Katharina Dach, Farina Bendt, Ulrike Huebenthal, Susanne Giersiefer, Pamela J Lein, Heike Heuer, Ellen Fritsche
Polybrominated diphenyl ethers (PBDEs) are bioaccumulating flame retardants causing developmental neurotoxicity (DNT) in humans and rodents. Their DNT effects are suspected to involve thyroid hormone (TH) signaling disruption. Here, we tested the hypothesis whether disturbance of neural progenitor cell (NPC) differentiation into the oligodendrocyte lineage (O4(+) cells) by BDE-99 involves disruption of TH action in human and mouse (h,m)NPCs. Therefore, we quantified differentiation of NPCs into O4(+) cells and measured their maturation via expression of myelin-associated genes (hMBP, mMog) in presence and absence of TH and/or BDE-99...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317340/production-of-pancreatic-progenitor-cells-from-human-induced-pluripotent-stem-cells-using-a-three-dimensional-suspension-bioreactor-system
#18
Yuichiro Mihara, Katsuhisa Matsuura, Yoshihiro Sakamoto, Teruo Okano, Norihiro Kokudo, Tatsuya Shimizu
Islet replacement is a promising strategy for the treatment of patients with type 1 diabetes and patients who have undergone total pancreatectomy. Recent progress in cellular reprogramming technology may allow the transplantation of a patient's own pancreatic cells. Although many studies have reported the differentiation of pancreatic progenitor cells from mouse and human pluripotent stem cells (PSCs), obtaining sufficient cell numbers for clinical applications remains problematic. Here, we describe the mass production of human pancreatic progenitor cells from human induced (i)PSCs using a three-dimensional suspension bioreactor system...
March 20, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28317180/anti-acsa-2-defines-a-novel-monoclonal-antibody-for-prospective-isolation-of-living-neonatal-and-adult-astrocytes
#19
Christina G Kantzer, Camille Boutin, Ina D Herzig, Carolina Wittwer, Sandy Reiß, Marie Catherine Tiveron, Jan Drewes, Thomas D Rockel, Stefanie Ohlig, Jovica Ninkovic, Harold Cremer, Sandra Pennartz, Melanie Jungblut, Andreas Bosio
Astrocytes are the most abundant cell type of the central nervous system and cover a broad range of functionalities. We report here the generation of a novel monoclonal antibody, anti-astrocyte cell surface antigen-2 (Anti-ACSA-2). Flow cytometry, immunohistochemistry and immunocytochemistry revealed that Anti-ACSA-2 reacted specifically with a not yet identified glycosylated surface molecule of murine astrocytes at all developmental stages. It did not show any labeling of non-astroglial cells such as neurons, oligodendrocytes, NG2(+) cells, microglia, endothelial cells, leukocytes, or erythrocytes...
March 20, 2017: Glia
https://www.readbyqxmd.com/read/28316325/silencing-of-the-small-gtpase-diras3-induces-cellular-senescence-in-human-white-adipose-stromal-progenitor-cells
#20
Asim Ejaz, Monika Mattesich, Werner Zwerschke
Inhibition of Akt-mTOR signaling protects from obesity and extends life span in animals. In the present study, we analyse the impact of the small GTPase, GTP-binding RAS-like 3 (DIRAS3), a recently identified weight-loss target gene, on cellular senescence in adipose stromal/progenitor cells (ASCs) derived from human subcutaneous white adipose tissue (sWAT). We demonstrate that DIRAS3 knock-down (KD) in ASCs induces activation of Akt-mTOR signaling and proliferation arrest. DIRAS3 KD ASCs lose the potential to form colonies and are negative for Ki-67...
March 17, 2017: Aging
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