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https://www.readbyqxmd.com/read/28924210/kinase-inhibitor-screening-using-artificial-neural-networks-and-engineered-cardiac-biowires
#1
Genevieve Conant, Samad Ahadian, Yimu Zhao, Milica Radisic
Kinase inhibitors are often used as cancer targeting agents for their ability to prevent the activation of cell growth and proliferation signals. Cardiotoxic effects have been identified for some marketed kinase inhibitors that were not detected during clinical trials. We hypothesize that more predictive cardiac functional assessments of kinase inhibitors on human myocardium can be established by combining a high-throughput two-dimensional (2D) screening assay and a high-content three-dimensional (3D) engineered cardiac tissue (Biowire(TM)) based assay, and using human induced pluripotent stem cell-derived CMs (hiPSC-CMs)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924182/an-in-vitro-model-of-lissencephaly-expanding-the-role-of-dcx-during-neurogenesis
#2
M Shahsavani, R J Pronk, R Falk, M Lam, M Moslem, S B Linker, J Salma, K Day, J Schuster, B-M Anderlid, N Dahl, F H Gage, A Falk
Lissencephaly comprises a spectrum of brain malformations due to impaired neuronal migration in the developing cerebral cortex. Classical lissencephaly is characterized by smooth cerebral surface and cortical thickening that result in seizures, severe neurological impairment and developmental delay. Mutations in the X-chromosomal gene DCX, encoding doublecortin, is the main cause of classical lissencephaly. Much of our knowledge about DCX-associated lissencephaly comes from post-mortem analyses of patient's brains, mainly since animal models with DCX mutations do not mimic the disease...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28923480/impact-of-morphine-on-the-expression-of-insulin-receptor-and-protein-levels-of-insulin-igfs-in-rat-neural-stem-cells
#3
Sadegh Salarinasab, AliReza Nourazarian, Masoud Nikanfar, Nima Abdyazdani, Masoumeh Kazemi, Navid Feizy, Reza Rahbarghazi
Alzheimer's disease is correlated with neuronal degeneration and loss of neuronal precursors in different parts of the brain. It has been found disturbance in the homeostasis neural stem cells (NSCs) can cause neurodegeneration. Morphine, an analgesic agent, can disrupt the dynamic and normal state of NSCs. However, more investigations are required to clearly address underlying mechanisms. The current experiment aimed to investigate the effects of morphine on the cell distribution of insulin factor and receptor and insulin-like growth factors (IGF1, IGF2) in NSCs...
September 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28922973/a-new-wnt1-cre-tomatorosa-es-cell-line-a-tool-for-studying-neural-crest-cell-integration-capacity
#4
Soledad Acuna Mendoza, Sabrina Martin, Sabine Kuchler-Bopp, Sandy Ribes, Jeremy H Thalgott, Catherine Chaussain, Sophie Creuzet, Hervé Lesot, Franck Lebrin, Anne Poliard
Neural crest (NC) cells are a migratory, multipotent population giving rise to numerous lineages in the embryo. Their plasticity renders attractive their use in tissue engineering-based therapies but further knowledge on their in vivo behaviour is required before clinical transfer may be envisioned. We here describe isolation and characterization of a new mouse ES line derived from Wnt1-CRE-R26 RosaTomatoTdv blastocyst and show that it displays the characteristics of typical ES cells. Furthermore, these cells can be efficiently directed towards a NC stem cell-like phenotype as attested by concomitant expression of NC marker genes and Tomato fluorescence...
September 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28922350/stem-cells-and-cell-based-therapies-for-cerebral-palsy-a-call-for-rigor
#5
REVIEW
Lauren L Jantzie, Joseph Scafidi, Shenandoah Robinson
Cell-based therapies hold significant promise for infants at risk for cerebral palsy (CP) from perinatal brain injury (PBI). PBI leading to CP results from multi-faceted damage to neural cells. Complex developing neural networks are injured by neural cell damage plus unique perturbations in cell signaling. Given that cell-based therapies can simultaneously repair multiple injured neural components during critical neurodevelopmental windows, these interventions potentially offer efficacy for patients with CP...
September 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28922152/brain-biomarkers-in-familial-alzheimer-s-disease-mouse-models
#6
Yafit Kuttner-Hirshler, Palamadai N Venkatasubramanian, Joan Apolinario, Jacqueline Bonds, Alice M Wyrwicz, Orly Lazarov
Alzheimer's disease (AD) is characterized by progressive loss of memory and cognitive deterioration. It is thought that the onset of the disease takes place several decades before memory deficits are apparent. Reliable biomarkers for the diagnosis or prognostication of the disease are highly desirable. Neural stem cells (NSC) exist in the adult brain throughout life and give rise to neural progenitor cells (NPC), which differentiate into neurons or glia. The level of NPC proliferation and new neuron formation is significantly compromised in mouse models of familial Alzheimer's disease (FAD)...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28921950/highly-efficient-and-rapid-neural-differentiation-of-mouse-embryonic-stem-cells-based-on-retinoic-acid-encapsulated-porous-nanoparticle
#7
Se-Jin Park, Seongchan Kim, Sung-Yon Kim, Noo Li Jeon, Joon Myong Song, Cheolhee Won, Dal-Hee Min
An improved cell conversion strategy for neural differentiation of mouse embryonic stem (mES) cells is developed by incorporating functionalized mesoporous silica nanoparticle (MSN) as an efficient delivery carrier of retinoic acid (RA), which is pleiotropic factor required for initiation of neural differentiation. Traditional RA-mediated neural differentiation methods required either pre-activation of the cells to the differentiating state by embryoid body (EB) formation or repetitive treatment of the differentiation factor...
September 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28919261/top-down-inhibition-of-bmp-signaling-enables-robust-induction-of-hpscs-into-neural-crest-in-fully-defined-xeno-free-conditions
#8
James O S Hackland, Tom J R Frith, Oliver Thompson, Ana Marin Navarro, Martin I Garcia-Castro, Christian Unger, Peter W Andrews
Defects in neural crest development have been implicated in many human disorders, but information about human neural crest formation mostly depends on extrapolation from model organisms. Human pluripotent stem cells (hPSCs) can be differentiated into in vitro counterparts of the neural crest, and some of the signals known to induce neural crest formation in vivo are required during this process. However, the protocols in current use tend to produce variable results, and there is no consensus as to the precise signals required for optimal neural crest differentiation...
September 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28918057/one-step-piggybac-transposon-based-crispr-cas9-activation-of-multiple-genes
#9
Shenglan Li, Anqi Zhang, Haipeng Xue, Dali Li, Ying Liu
Neural cell fate is determined by a tightly controlled transcription regulatory network during development. The ability to manipulate the expression of multiple transcription factors simultaneously is required to delineate the complex picture of neural cell development. Because of the limited carrying capacity of the commonly used viral vectors, such as lentiviral or retroviral vectors, it is often challenging to perform perturbation experiments on multiple transcription factors. Here we have developed a piggyBac (PB) transposon-based CRISPR activation (CRISPRa) all-in-one system, which allows for simultaneous and stable endogenous transactivation of multiple transcription factors and long non-coding RNAs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916193/ferulic-acid-promotes-survival-and-differentiation-of-neural-stem-cells-to-prevent-gentamicin-induced-neuronal-hearing-loss
#10
Lintao Gu, Xinhua Cui, Wei Wei, Jia Yang, Xuezhong Li
Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed...
September 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28914887/neural-repair-and-rehabilitation-prolonged-neural-stem-cell-maturation-restores-motor-function-in-spinal-cord-lesioned-rats
#11
Mitesh Patel
No abstract text is available yet for this article.
September 15, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28914133/age-of-donor-of-human-mesenchymal-stem-cells-affects-structural-and-functional-recovery-after-cell-therapy-following-ischaemic-stroke
#12
Susumu Yamaguchi, Nobutaka Horie, Katsuya Satoh, Takeshi Ishikawa, Tsuyoshi Mori, Hajime Maeda, Yuhtaka Fukuda, Shunsuke Ishizaka, Takeshi Hiu, Yoichi Morofuji, Tsuyoshi Izumo, Noriyuki Nishida, Takayuki Matsuo
Cell transplantation therapy offers great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is unclear. We investigated the regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischaemic stroke. The quantities of human mesenchymal stem cell (hMSC) secreted brain-derived neurotrophic factor in vitro and of monocyte chemotactic protein-1 at day 7 in vivo were both significantly higher for young hMSC compared with old hMSC...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28913777/diabetes-and-the-small-intestine
#13
REVIEW
Jonathan Gotfried, Stephen Priest, Ron Schey
Diabetes mellitus (DM) and its associated complications are becoming increasingly prevalent. Gastrointestinal symptoms associated with diabetes is known as diabetic enteropathy (DE) and may manifest as either diarrhea, fecal incontinence, constipation, dyspepsia, nausea, and vomiting or a combination of symptoms. The long-held belief that vagal autonomic neuropathy is the primary cause of DE has recently been challenged by newer theories of disease development. Specifically, hyperglycemia and the resulting oxidative stress on neural networks, including the nitrergic neurons and interstitial cells of Cajal (ICC), are now believed to play a central role in the development of DE...
September 15, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28913662/effects-of-short-term-exposure-to-sevoflurane-on-the-survival-proliferation-apoptosis-and-differentiation-of-neural-precursor-cells-derived-from-human-embryonic-stem-cells
#14
Jin-Woo Park, Mi-Sun Lim, So Yeon Ji, Myung Soo Cho, Seong-Joo Park, Sung-Hee Han, Jin-Hee Kim
PURPOSE: Data from animal experiments suggest that exposure to general anesthetics in early life inhibits neurogenesis and causes long-term memory deficit. Considering short operating times and the popularity of sevoflurane in pediatric anesthesia, it is important to verify the effects of short-period exposure to sevoflurane on the developing brain. METHODS: We measured the effects of short-term exposure (2 h) to 3%, 6%, or 8% sevoflurane, the most commonly used anesthetic, on neural precursor cells derived from human embryonic stem cells, SNUhES32...
September 14, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28912571/comparative-global-immune-related-gene-profiling-of-somatic-cells-human-pluripotent-stem-cells-and-their-derivatives-implication-for-human-lymphocyte-proliferation
#15
Chia-Eng Wu, Chen-Wei Yu, Kai-Wei Chang, Wen-Hsi Chou, Chen-Yu Lu, Elisa Ghelfi, Fang-Chun Wu, Pey-Shynan Jan, Mei-Chi Huang, Patrick Allard, Shau-Ping Lin, Hong-Nerng Ho, Hsin-Fu Chen
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity...
September 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28911165/cellular-retinoic-acid-binding-protein-1-modulates-stem-cell-proliferation-to-affect-learning-and-memory-in-male-mice
#16
Yu-Lung Lin, Shawna D Persaud, Jennifer Nhieu, Li-Na Wei
Retinoic acid (RA) is the active ingredient of vitamin A. It exerts its canonical activity by binding to nuclear RA receptors (RARs) to regulate gene expression. Increasingly, RA is also known to elicit nongenomic RAR-independent activities, most widely detected in activating extracellular regulated kinase (ERK)1/2. This study validated the functional role of cellular retinoic acid-binding protein 1 (Crabp1) in mediating nongenomic activity in RA, specifically activating ERK1/2 to rapidly augment the cell cycle by expanding the growth 1 phase and slowing down embryonic stem cell and neural stem cell (NSC) proliferation...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28904534/three-dimensional-organoid-system-transplantation-technologies-in-future-treatment-of-central-nervous-system-diseases
#17
REVIEW
NaiLi Wei, ZiFang Quan, Hailiang Tang, JianHong Zhu
In recent years, scientists have made great achievements in understanding the development of human brain and elucidating critical elements of stepwise spatiotemporal control strategies in neural stem cell specification lineage, which facilitates successful induction of neural organoid in vitro including the cerebral cortex, cerebellar, neural tube, hippocampus cortex, pituitary, and optic cup. Besides, emerging researches on neural organogenesis promote the application of 3D organoid system transplantation in treating central nervous system (CNS) diseases...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28904337/toxoplasma-modulates-signature-pathways-of-human-epilepsy-neurodegeneration-cancer
#18
Huân M Ngô, Ying Zhou, Hernan Lorenzi, Kai Wang, Taek-Kyun Kim, Yong Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Seesandra V Rajagopala, Craig W Roberts, Fiona L Henriquez, Alexandre Montpetit, Jenefer M Blackwell, Sarra E Jamieson, Kelsey Wheeler, Ian J Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez, Roderick G Davis, Liliana Soroceanu, Charles Cobbs, Dennis A Steindler, Kenneth Boyer, A Gwendolyn Noble, Charles N Swisher, Peter T Heydemann, Peter Rabiah, Shawn Withers, Patricia Soteropoulos, Leroy Hood, Rima McLeod
One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28903548/role-of-the-unfolded-protein-response-in-the-development-of-central-nervous-system
#19
Naoya Murao, Hideki Nishitoh
The unfolded protein response (UPR) is an intracellular homeostatic signalling pathway that is induced by accumulated misfolded/unfolded proteins in the endoplasmic reticulum (ER). The UPR is closely associated with the development of disease in several tissues, including the central nervous system (CNS), in response to ER stress. More recently, the unique features and importance of the UPR have been revealed in neural stem cells (NSCs) and differentiated CNS cells [neurons and glial cells (astrocytes and oligodendrocytes)]...
September 1, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28903496/editor-s-highlight-development-of-novel-neural-embryonic-stem-celltests-for-high-throughput-screening-of-embryotoxic-chemicals
#20
Kumiko Kobayashi, Noriyuki Suzuki, Kiyoshi Higashi, Akane Muroi, Florian Le Coz, Hirohisa Nagahori, Koichi Saito
There is a great demand for appropriate alternative methods to rapidly evaluate the developmental and reproductive toxicity of a wide variety of chemicals. We used the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes as a basis for establishing a rapid and highly reproducible invitro embryotoxicity test known as the Hand1-Luc Embryonic Stem Cell Test (Hand1-Luc EST). In this study, we developed novel neural-Luc ESTs using two marker genes for neural development, tubulin beta-3 (Tubb3) and Reelin (Reln), and evaluated the capacity of these tests to predict developmental toxicity...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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