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https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#1
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28505164/human-decellularized-bone-scaffolds-from-aged-donors-show-improved-osteoinductive-capacity-compared-to-young-donor-bone
#2
Christopher A Smith, Tim N Board, Paul Rooney, Mark J Eagle, Stephen M Richardson, Judith A Hoyland
To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC) osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC)...
2017: PloS One
https://www.readbyqxmd.com/read/28501647/application-of-optical-action-potentials-in-human-induced-pluripotent-stem-cells-derived-cardiomyocytes-to-predict-drug-induced-cardiac-arrhythmias
#3
H R Lu, M P Hortigon-Vinagre, V Zamora, I Kopljar, A De Bondt, D J Gallacher, G Smith
INTRODUCTION: Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. METHODS: Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds...
May 10, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28491099/induction-of-pluripotent-stem-cells-from-a-manifesting-carrier-of-duchenne-muscular-dystrophy-and-characterization-of-their-x-inactivation-status
#4
Yuko Miyagoe-Suzuki, Takashi Nishiyama, Miho Nakamura, Asako Narita, Fusako Takemura, Satoru Masuda, Narihiro Minami, Kumiko Murayama, Hirofumi Komaki, Yu-Ichi Goto, Shin'ichi Takeda
Three to eight percent of female carriers of Duchenne muscular dystrophy (DMD) develop dystrophic symptoms ranging from mild muscle weakness to a rapidly progressive DMD-like muscular dystrophy due to skewed inactivation of X chromosomes during early development. Here, we generated human induced pluripotent stem cells (hiPSCs) from a manifesting female carrier using retroviral or Sendai viral (SeV) vectors and determined their X-inactivation status. Although manifesting carrier-derived iPS cells showed normal expression of human embryonic stem cell markers and formed well-differentiated teratomas in vivo, many hiPS clones showed bi-allelic expression of the androgen receptor (AR) gene and loss of X-inactivation-specific transcript and trimethyl-histone H3 (Lys27) signals on X chromosomes, suggesting that both X chromosomes of the hiPS cells are in an active state...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28481220/mrna-mediated-glycoengineering-ameliorates-deficient-homing-of-human-stem-cell-derived-hematopoietic-progenitors
#5
Jungmin Lee, Brad Dykstra, Joel A Spencer, Laurie L Kenney, Dale L Greiner, Leonard D Shultz, Michael A Brehm, Charles P Lin, Robert Sackstein, Derrick J Rossi
Generation of functional hematopoietic stem and progenitor cells (HSPCs) from human pluripotent stem cells (PSCs) has been a long-sought-after goal for use in hematopoietic cell production, disease modeling, and eventually transplantation medicine. Homing of HSPCs from bloodstream to bone marrow (BM) is an important aspect of HSPC biology that has remained unaddressed in efforts to derive functional HSPCs from human PSCs. We have therefore examined the BM homing properties of human induced pluripotent stem cell-derived HSPCs (hiPS-HSPCs)...
May 8, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28461922/bone-grafts-bone-graft-extenders-substitutes-and-enhancers-for-acetabular-reconstruction-in-revision-total-hip-arthroplasty
#6
REVIEW
Luca Pierannunzii, Luigi Zagra
Acetabular bone loss is a relevant concern for surgeons dealing with a failed total hip arthroplasty.Since the femoral head is no longer available, allografts represent the first choice for most reconstructive solutions, either as a structural buttress or impacted bone chips.Even though fresh-frozen bone is firmly recommended for structural grafts, freeze-dried and/or irradiated bone may be used alternatively for impaction grafting. Indeed, there are some papers on freeze-dried or irradiated bone impaction grafting, but their number is limited, as is the number of cases...
December 2016: EFORT Open Rev
https://www.readbyqxmd.com/read/28423718/itraq-based-quantitative-proteomic-analysis-of-yamanaka-factors-reprogrammed-breast-cancer-cells
#7
Kun Wang, Zhiyan Shan, Lian Duan, Tiantian Gong, Feng Liu, Yue Zhang, Zhendong Wang, Jingling Shen, Lei Lei
Cancer cells had been developed to be reprogrammed into embryonic stem like cells by induced pluripotent stem cells (iPSCs) technology, however, the tumor differentiation/dedifferentiation mechanisms had not yet been analyzed on a genome-wide scale. Here, we inserted the four stem cell transcription factor genes OCT4, SOX2, C-MYC and KLF4 into MCF cells (MCFs), represented a female breast cancer cell type, and obtained iPSCs (Mcfips) in about 3 weeks. By using the LC MS/MS iTRAQ technology, we analyzed the proteomic changes between MCFs and Mcfips...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420864/insulin-growth-factor-1-protects-neural-stem-cells-against-apoptosis-induced-by-hypoxia-through-akt-mitogen-activated-protein-kinase-extracellular-signal-regulated-kinase-akt-mapk-erk-pathway-in-hypoxia-ishchemic-encephalopathy
#8
Bing Zhao, Zebao Zheng
BACKGROUND Insulin growth factor 1 (IGF-1) is reported to modulate cell growth and acts as potential therapy for traumatic brain injury. This study was designed to investigate the effect of IGF-1 on hypoxia-induced apoptosis in neural stem cells (NSCs). MATERIAL AND METHODS A hypoxia model was constructed using NSCs separated from the hippocampus of rat. NSCs were divided into four groups: cells under normoxic conditions that acted as controls (C group), cells under hypoxia (H group), cells under hypoxia with IGF-1 (HI group), and cells under hypoxia with IGF-1 as well as picropodophyllin (PPP), which acts as an inhibitor of the IGF-1 receptor (HIP group)...
April 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28395796/derivation-of-human-ips-cell-lines-from-monozygotic-twins-in-defined-and-xeno-free-conditions
#9
Elias Uhlin, Harriet Rönnholm, Kelly Day, Malin Kele, Kristiina Tammimies, Sven Bölte, Anna Falk
Human induced pluripotent stem (hiPS) cell lines CTRL-9-II and CTRL-10-I were derived from healthy monozygotic twin donors using non-integrating RNA based Sendai virus reprogramming and cultured in a xeno-free chemically defined condition. The established hiPS cell lines, CTRL-9-II and CTRL-10-I, are karyotypically normal, free from reprogramming vectors, display endogenously expression of pluripotency factors at levels similar to embryonic stem cells. The generated iPS cell lines demonstrate pluripotency by passing bioinformatics assay PluriTest and by embryonic body assay...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28395738/a-feeder-and-xeno-free-human-induced-pluripotent-stem-cell-line-obtained-from-primary-human-dermal-fibroblasts-with-epigenetic-repression-of-reprogramming-factors-expression-gpcci001-a
#10
Michał Stefan Lach, Joanna P Wroblewska, Ewelina Augustyniak, Katarzyna Kulcenty, Wiktoria Maria Suchorska
The primary human dermal fibroblasts (PHDFs) from breast cancer patient were obtained to generate the human induced pluripotent stem cell line GPCCi001-A via lentiviral transfection. Thus, a modified EF1a-hSTEMCCA-loxP with tetO operator which regulates transgene expression was used. This method takes advantage of epigenetic regulation of transcription and allows for stable silencing of the reprogramming factors in obtained hiPS cells. To increase the potential utility of hiPSCs for clinical applications, they were adapted to feeder- and xeno-free conditions...
April 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28351853/pharmaceutical-characterization-of-tropomyosin-receptor-kinase-b-agonistic-antibodies-on-human-ips-cell-derived-neurons
#11
Stefanie Traub, Heiko Stahl, Holger Rosenbrock, Eric Simon, Lore Florin, Lisa Hospach, Stefan Hoerer, Ralf Heilker
Brain-derived neurotrophic factor (BDNF) is a central modulator of neuronal development and synaptic plasticity in the central nervous system (CNS). This renders the BDNF-modulated tropomyosin receptor kinase B (TrkB) a promising drug target to treat synaptic dysfunctions. Using GRowth factor-driven expansion and INhibition of NotCH during maturation, the so-called GRINCH neurons were derived from human induced pluripotent stem (hiPS) cells. These GRINCH neurons were employed as model cells for pharmacological profiling of two TrkB-agonistic antibodies, hereafter referred to as AB2 and AB20...
March 28, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28340154/irradiation-strongly-reduces-tumorigenesis-of-human-induced-pluripotent-stem-cells
#12
Shoki Inui, Kazumasa Minami, Emiko Ito, Hiromasa Imaizumi, Seiji Mori, Masahiko Koizumi, Satsuki Fukushima, Shigeru Miyagawa, Yoshiki Sawa, Nariaki Matsuura
Induced pluripotent stem (iPS) cells have demonstrated they can undergo self-renewal, attain pluripotency, and differentiate into various types of functional cells. In clinical transplantation of iPS cells, however, a major problem is the prevention of tumorigenesis. We speculated that tumor formation could be inhibited by means of irradiation. Since the main purpose of this study was to explore the prevention of tumor formation in human iPS (hiPS) cells, we tested the effects of irradiation on tumor-associated factors such as radiosensitivity, pluripotency and cell death in hiPS cells...
March 3, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28326353/in-vitro-osteogenic-capacity-of-bone-marrow-mscs-from-postmenopausal-women-reflect-the-osseointegration-of-their-cementless-hip-stems
#13
Jessica J Alm, Niko Moritz, Hannu T Aro
Age-related dysfunction of mesenchymal stromal cells (MSCs) is suggested as a main cause of altered bone repair with aging. We recently showed that in postmenopausal women undergoing cementless total hip arthroplasty (THA) aging, low bone mineral density (BMD) and age-related geometric changes of the proximal femur are risk factors for increased early migration and delayed osseointegration of the femoral stems. Extending these analyses, we have here explored how the in vitro osteogenic capacity of bone marrow MSCs from these patients reflects implant osseointegration, representing the patient's in vivo bone healing capacity...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28321048/evaluation-of-the-effects-of-power-frequency-magnetic-fields-on-the-electrical-activity-of-cardiomyocytes-differentiated-from-human-induced-pluripotent-stem-cells
#14
Masayuki Takahashi, Atsushi Saito, Yasuhiko Jimbo, Satoshi Nakasono
Although cardiac activity is known to differ between species in many respects, most evaluations of the cardiac effects of low-frequency electric and magnetic fields, which have a stimulant effect on electrically activated cells, have been performed in non-human experimental animals and cells, and the effects in humans have been assessed using theoretical models. In recent years, it has been verified that human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CM) are useful for evaluating human responses to various cardioactive compounds...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28290232/retention-of-human-induced-pluripotent-stem-cells-hips-with-injectable-ha-hydrogels-for-vocal-fold-engineering
#15
Mitsuyoshi Imaizumi, Nicole Y K Li-Jessen, Yuka Sato, David T Yang, Susan L Thibeault
OBJECTIVE: One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds. METHODS: Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls...
April 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/28256115/serum-preadipocyte-factor-1-levels-are-not-associated-with-bone-mineral-density-among-healthy-postmenopausal-korean-women
#16
Hoon Sung Choi, Sang Wook Kim, Eun Hee Cho
BACKGROUND: Multipotent mesenchymal stem cells can differentiate into adipocytes or osteoblasts through closely regulated lineage-control processes. However, adipocyte precursor cells release preadipocyte factor 1 (Pref-1), which inhibits the differentiation of mesenchymal stem cells into mature adipocytes and osteoblasts. Previous studies have also reported an inverse association between Pref-1 levels and bone mineral density (BMD) among patients with anorexia nervosa. METHODS: In this retrospective study, we examined the correlations between Pref-1 levels and BMD among 124 healthy postmenopausal women (>50 years old)...
March 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28246930/association-of-plasma-sdf-1-with-bone-mineral-density-body-composition-and-hip-fractures-in-older-adults-the-cardiovascular-health-study
#17
Laura D Carbone, Petra Bůžková, Howard A Fink, John A Robbins, Monique Bethel, Mark W Hamrick, William D Hill
Aging is associated with an increase in circulating inflammatory factors. One, the cytokine stromal cell-derived factor 1 (SDF-1 or CXCL12), is critical to stem cell mobilization, migration, and homing as well as to bone marrow stem cell (BMSC), osteoblast, and osteoclast function. SDF-1 has pleiotropic roles in bone formation and BMSC differentiation into osteoblasts/osteocytes, and in osteoprogenitor cell survival. The objective of this study was to examine the association of plasma SDF-1 in participants in the cardiovascular health study (CHS) with bone mineral density (BMD), body composition, and incident hip fractures...
February 28, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28231034/upscaling-of-hips-cell-derived-neurons-for-high-throughput-screening
#18
Stefanie Traub, Heiko Stahl, Holger Rosenbrock, Eric Simon, Ralf Heilker
The advent of human-induced pluripotent stem (hiPS) cell-derived neurons promised to provide better model cells for drug discovery in the context of the central nervous system. This work demonstrates both the upscaling of cellular expansion and the acceleration of neuronal differentiation to accommodate the immense material needs of a high-throughput screening (HTS) approach. Using GRowth factor-driven expansion and INhibition of NotCH (GRINCH) during maturation, the derived cells are here referred to as GRINCH neurons...
March 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28191778/generation-of-human-induced-pluripotent-stem-cell-derived-bona-fide-neural-stem-cells-for-ex-vivo-gene-therapy-of-metachromatic-leukodystrophy
#19
Vasco Meneghini, Giacomo Frati, Davide Sala, Silvia De Cicco, Marco Luciani, Chiara Cavazzin, Marianna Paulis, Wieslawa Mentzen, Francesco Morena, Serena Giannelli, Francesca Sanvito, Anna Villa, Alessandro Bulfone, Vania Broccoli, Sabata Martino, Angela Gritti
Allogeneic fetal-derived human neural stem cells (hfNSCs) that are under clinical evaluation for several neurodegenerative diseases display a favorable safety profile, but require immunosuppression upon transplantation in patients. Neural progenitors derived from patient-specific induced pluripotent stem cells (iPSCs) may be relevant for autologous ex vivo gene-therapy applications to treat genetic diseases with unmet medical need. In this scenario, obtaining iPSC-derived neural stem cells (NSCs) showing a reliable "NSC signature" is mandatory...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28174491/comprehensive-evaluation-of-nutritional-status-before-and-after-hematopoietic-stem-cell-transplantation-in-170-patients-with-hematological-diseases
#20
Peng Liu, Boshi Wang, Xia Yan, Jingjing Cai, Yu Wang
OBJECTIVE: To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation (HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases. METHODS: This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May 2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002), Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA) and Malnutrition Universal Screening Tools (MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
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