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https://www.readbyqxmd.com/read/27916837/chloroquine-an-endocytosis-blocking-agent-inhibits-zika-virus-infection-in-different-cell-models
#1
Rodrigo Delvecchio, Luiza M Higa, Paula Pezzuto, Ana Luiza Valadão, Patrícia P Garcez, Fábio L Monteiro, Erick C Loiola, André A Dias, Fábio J M Silva, Matthew T Aliota, Elizabeth A Caine, Jorge E Osorio, Maria Bellio, David H O'Connor, Stevens Rehen, Renato Santana de Aguiar, Andrea Savarino, Loraine Campanati, Amilcar Tanuri
Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres...
November 29, 2016: Viruses
https://www.readbyqxmd.com/read/27916472/generation-of-neural-cells-using-ipscs-from-sleep-bruxism-patients-with-5-ht2a-polymorphism
#2
Yurie Hoashi, Satoshi Okamoto, Yuka Abe, Takashi Matsumoto, Junichi Tanaka, Yuya Yoshida, Kent Imaizumi, Kenji Mishima, Wado Akamatsu, Hideyuki Okano, Kazuyoshi Baba
PURPOSE: Sleep bruxism (SB) is classified as a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep, which is responsible for a variety of clinical problems such as abnormal tooth attrition and fracture of teeth or roots. Little is known about the etiology of SB. Our previous study identified a genomic association of the serotonin 2A receptor (5-HT2A) single nucleotide polymorphism (SNP), rs6313 C>T, with SB, where the C allele carrier is associated with a 4...
December 1, 2016: Journal of Prosthodontic Research
https://www.readbyqxmd.com/read/27909720/tetrandrine-inhibits-glioma-stem-like-cells-by-repressing-%C3%AE-catenin-expression
#3
Yong Zhang, Yu-Lin Wen, Ji-Wei Ma, Jie-Cheng Ye, Xiao Wang, Jian-Xian Huang, Chao-Yue Meng, Xiao-Ze Xu, Shao-Xiang Wang, Xue-Yun Zhong
Cancer stem cells (CSCs) in glioma are often responsible for relapse and resistance to therapy. The purpose of the present study was to confirm the self-renewal and migration inhibitory effects of tetrandrine (Tet), which is a compound extracted from the dried root of Stephania tetrandra S. Moore, toward glioma stem-like cells (GSLCs) and to examine the associated molecular mechanisms. Using a neurosphere culture technique, we enriched the GSLC population from the human glioblastoma cell lines U87 and U251...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27903708/astrocyte-elevated-gene-1-regulates-beta-catenin-signaling-to-maintain-glioma-stem-like-stemness-and-self-renewal
#4
Bin Hu, Luni Emdad, Timothy P Kegelman, Xue-Ning Shen, Swadesh K Das, Devanand Sarkar, Paul B Fisher
: Glioblastoma multiforme (GBM) is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSCs) are responsible for GBM escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers including GBM, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology...
November 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27893719/novel-kdm1a-inhibitors-induce-differentiation-and-apoptosis-of-glioma-stem-cells-via-unfolded-protein-response-pathway
#5
G R Sareddy, S Viswanadhapalli, P Surapaneni, T Suzuki, A Brenner, R K Vadlamudi
Glioma stem cells (GSCs) have a central role in glioblastoma (GBM) development and chemo/radiation resistance, and their elimination is critical for the development of efficient therapeutic strategies. Recently, we showed that lysine demethylase KDM1A is overexpressed in GBM. In the present study, we determined whether KDM1A modulates GSCs stemness and differentiation and tested the utility of two novel KDM1A-specific inhibitors (NCL-1 and NCD-38) to promote differentiation and apoptosis of GSCs. The efficacy of KDM1A targeting drugs was tested on purified GSCs isolated from established and patient-derived GBMs using both in vitro assays and in vivo orthotopic preclinical models...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27884342/optimizing-neurogenic-potential-of-enteric-neurospheres-for-treatment-of-neurointestinal-diseases
#6
Lily S Cheng, Hannah K Graham, Wei Hua Pan, Nandor Nagy, Alfonso Carreon-Rodriguez, Allan M Goldstein, Ryo Hotta
BACKGROUND: Enteric neurospheres derived from postnatal intestine represent a promising avenue for cell replacement therapy to treat Hirschsprung disease and other neurointestinal diseases. We describe a simple method to improve the neuronal yield of spontaneously formed gut-derived neurospheres. MATERIALS AND METHODS: Enteric neurospheres were formed from the small and large intestines of mouse and human subjects. Neurosphere size, neural crest cell content, cell migration, neuronal differentiation, and neuronal proliferation in culture were analyzed...
December 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27862183/the-antiviral-cytokine-interferon-gamma-restricts-neural-stem-progenitor-cell-proliferation-through-activation-of-stat1-and-modulation-of-retinoblastoma-protein-phosphorylation
#7
Apurva Kulkarni, Taylor J Scully, Lauren A O'Donnell
Neural stem/progenitor cells (NPSCs) express receptors for many inflammatory cytokines, with varying effects on differentiation and proliferation depending on the stage of development and the milieu of inflammatory mediators. In primary neurons and astrocytes, we recently showed that interferon gamma (IFNγ), a potent antiviral cytokine that is required for the control and clearance of many central nervous system (CNS) infections, could differentially affect cell survival and cell cycle progression depending upon the cell type and the profile of activated intracellular signaling molecules...
November 15, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27859025/modeling-drug-induced-neuropathy-using-human-ipscs-for-predictive-toxicology
#8
Ryo Ohara, Keiko Imamura, Fukiko Morii, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Ran Shibukawa, Toshiki Mizuno, Masanori Nakagawa, Haruhisa Inoue
Drugs under development can cause unpredicted toxicity in humans due to differential drug responsiveness between humans and other disease models, resulting in clinical trial failures. Human induced pluripotent stem cells (iPSCs) are expected to represent a useful tool for toxicity testing. However, among many assays, appropriate cellular assays for predicting neurotoxicity in an iPSC-based model are still uncertain. Here, we generated neurons from iPSCs of Charcot-Marie-Tooth disease (CMT) patients, who are sensitive to anti-cancer drugs and present with the adverse reaction of neuropathy, and analyzed cellular phenotypes...
November 9, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27829215/rsk2-activity-mediates-glioblastoma-invasiveness-and-is-a-potential-target-for-new-therapeutics
#9
Florian J Sulzmaier, Shirley Young-Robbins, Pengfei Jiang, Dirk Geerts, Amanda M Prechtl, Michelle L Matter, Santosh Kesari, Joe W Ramos
In glioblastoma (GBM), infiltration of primary tumor cells into the normal tissue and dispersal throughout the brain is a central challenge to successful treatment that remains unmet. Indeed, patients respond poorly to the current therapies of tumor resection followed by chemotherapy with radiotherapy and have only a 16-month median survival. It is therefore imperative to develop novel therapies. RSK2 is a kinase that regulates proliferation and adhesion and can promote metastasis. We demonstrate that active RSK2 regulates GBM cell adhesion and is essential for cell motility and invasion of patient-derived GBM neurospheres...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825148/creating-interactions-between-tissue-engineered-skeletal-muscle-and-the-peripheral-nervous-system
#10
Alec S T Smith, Samantha L Passey, Neil R W Martin, Darren J Player, Vivek Mudera, Linda Greensmith, Mark P Lewis
Effective models of mammalian tissues must allow and encourage physiologically (mimetic) correct interactions between co-cultured cell types in order to produce culture microenvironments as similar as possible to those that would normally occur in vivo. In the case of skeletal muscle, the development of such a culture model, integrating multiple relevant cell types within a biomimetic scaffold, would be of significant benefit for investigations into the development, functional performance, and pathophysiology of skeletal muscle tissue...
2016: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/27818039/regenerative-potential-of-ependymal-cells-for-spinal-cord-injuries-over-time
#11
Xiaofei Li, Elisa M Floriddia, Konstantinos Toskas, Karl J L Fernandes, Nicolas Guérout, Fanie Barnabé-Heider
Stem cells have a high therapeutic potential for the treatment of spinal cord injury (SCI). We have shown previously that endogenous stem cell potential is confined to ependymal cells in the adult spinal cord which could be targeted for non-invasive SCI therapy. However, ependymal cells are an understudied cell population. Taking advantage of transgenic lines, we characterize the appearance and potential of ependymal cells during development. We show that spinal cord stem cell potential in vitro is contained within these cells by birth...
October 28, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27809850/the-association-and-significance-of-h3k27me3-and-a-folate-metabolic-gene-acat2-in-neural-tube-defects
#12
Sifan Zhai, Mingzuo Zhao, Changcheng Zhou, Fenggang Lu, Huankai Zhang, Li Na, Shanshan Feng, Xiaoxin Qiang, Yong Du
AIM: To study the association between the expression of H3K27me3 and ACat2 (a folate metabolic protein), in order to elucidate the protective mechanism of folic acid (FA) in neural tube defects (NTDs). METHODS: Eighteen female SD rats were randomly divided into normal, NTD and FA group. NTD group was induced by all-trans retinoic acid (ATRA) at E10d. FA group was fed with FA supplementation since 2 weeks before pregnancy, followed by ATRA induction. At E15d, FA level in the embryonic neural tube was determined by ELISA...
November 3, 2016: Nutrition Journal
https://www.readbyqxmd.com/read/27807176/hiv-tat-impairs-neurogenesis-through-functioning-as-a-notch-ligand-and-activation-of-notch-signaling-pathway
#13
Yan Fan, Xiang Gao, Jinhui Chen, Ying Liu, Johnny J He
: Alterations in adult neurogenesis have been noted in the brain of HIV-infected individuals and are likely linked to HIV-associated neurocognitive deficits, including those in learning and memory. But the underlying molecular mechanisms are not fully understood. In the study, we took advantage of doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) and determined the relationship between Tat expression and neurogenesis. Tat expression in astrocytes was associated with fewer neuron progenitor cells (NPCs), fewer immature neurons, and fewer mature neurons in the dentate gyrus of the hippocampus of the mouse brain...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27801899/analysis-of-induced-pluripotent-stem-cells-carrying-22q11-2-deletion
#14
M Toyoshima, W Akamatsu, Y Okada, T Ohnishi, S Balan, Y Hisano, Y Iwayama, T Toyota, T Matsumoto, N Itasaka, S Sugiyama, M Tanaka, M Yano, B Dean, H Okano, T Yoshikawa
Given the complexity and heterogeneity of the genomic architecture underlying schizophrenia, molecular analyses of these patients with defined and large effect-size genomic defects could provide valuable clues. We established human-induced pluripotent stem cells from two schizophrenia patients with the 22q11.2 deletion (two cell lines from each subject, total of four cell lines) and three controls (total of four cell lines). Neurosphere size, neural differentiation efficiency, neurite outgrowth, cellular migration and the neurogenic-to-gliogenic competence ratio were significantly reduced in patient-derived cells...
November 1, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27799894/deciphering-the-role-of-emx1-in-neurogenesis-a-neuroproteomics-approach
#15
Firas H Kobeissy, Katharina Hansen, Melanie Neumann, Shuping Fu, Kulin Jin, Jialing Liu
Emx1 has long been implicated in embryonic brain development. Previously we found that mice null of Emx1 gene had smaller dentate gyri and reduced neurogenesis, although the molecular mechanisms underlying this defect was not well understood. To decipher the role of Emx1 gene in neural regeneration and the timing of its involvement, we determine the frequency of neural stem cells (NSCs) in embryonic and adult forebrains of Emx1 wild type (WT) and knock out (KO) mice in the neurosphere assay. Emx1 gene deletion reduced the frequency and self-renewal capacity of NSCs of the embryonic brain but did not affect neuronal or glial differentiation...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27791206/metformin-treatment-reduces-temozolomide-resistance-of-glioblastoma-cells
#16
Seung Ho Yang, Shenglan Li, Guangrong Lu, Haipeng Xue, Dong H Kim, Jay-Jiguang Zhu, Ying Liu
It has been reported that metformin acts synergistically with temozolomide (TMZ) to inhibit proliferation of glioma cells including glioblastoma multiforme (GBM). However, the molecular mechanism underlying how metformin exerts its anti-cancer effects remains elusive. We used a combined experimental and bioinformatics approach to identify genes and complex regulatory/signal transduction networks that are involved in restoring TMZ sensitivity of GBM cells after metformin treatment. First, we established TMZ resistant GBM cell lines and found that the resistant cells regained TMZ sensitivity after metformin treatment...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27790794/p27kip1-is-required-for-functionally-relevant-adult-hippocampal-neurogenesis-in-mice
#17
Henrik Hörster, Alexander Garthe, Tara L Walker, Muhammad Ichwan, Barbara Steiner, M Amir Khan, D Chichung Lie, Zeina Nicola, Gerardo Ramirez-Rodriguez, Gerd Kempermann
We asked whether cell-cycle associated protein p27kip1 might be involved in the transition of precursor cells to postmitotic maturation in adult hippocampal neurogenesis. p27kip1 was expressed throughout the dentate gyrus with a strong nuclear expression in early postmitotic, calretinin-positive neurons and neuronally determined progenitor cells (type-3 and some type-2b), lower or absent expression in radial glia-like precursor cells (type-1) and type-2a cells and essentially no expression in granule cells...
October 28, 2016: Stem Cells
https://www.readbyqxmd.com/read/27779678/heb-silencing-induces-anti-proliferative-effects-on-u87mg-cells-cultured-as-neurospheres-and-monolayers
#18
Paulo R D V Godoy, Ana Paula L Montaldi, Elza T Sakamoto-Hojo
Glioblastoma multiforme (GBM) is a lethal tumor and novel strategies are required to overcome resistance. Transcription factor 12 (HEB) has been associated with neural and stem cell proliferation, is overexpressed in certain tumor types and is induced in irradiated U87MG cells. The present study aimed to determine whether HEB knockdown, with or without irradiation, may sensitize GBM cells. U87MG GBM and ACBRI‑371 primary human astrocytes were cultured in monolayers or neurospheres. Cell proliferation and death, cell cycle and sub‑G1 detection, and cluster of differentiation (CD) 133 immunofluorescence were analyzed by flow cytometry, whereas HEB protein expression was analyzed by immunocytochemistry and western blotting...
October 21, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27770487/medial-ganglionic-eminence-cells-freshly-obtained-or-expanded-as-neurospheres-show-distinct-cellular-and-molecular-properties-in-reducing-epileptic-seizures
#19
Simone A A Romariz, Daisyléa S Paiva, Layla T Galindo, Gabriela F Barnabé, Vivian A Guedes, Cesario V Borlongan, Beatriz M Longo
AIMS: Medial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large-scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the culture medium of MGE neurospheres affect neuronal differentiation and expression of MGE-specific genes. In vivo, we compared anticonvulsant effects and cell differentiation pattern among neurospheres grown in different culture media and compared them with freshly harvested MGE cells...
October 21, 2016: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27768074/enumeration-of-neural-stem-cells-using-clonal-assays
#20
Gunaseelan Narayanan, Yuan Hong Yu, Muly Tham, Hui Theng Gan, Srinivas Ramasamy, Shvetha Sankaran, Srivats Hariharan, Sohail Ahmed
Neural stem cells (NSCs) have the ability to self-renew and generate the three major neural lineages - astrocytes, neurons and oligodendrocytes. NSCs and neural progenitors (NPs) are commonly cultured in vitro as neurospheres. This protocol describes in detail how to determine the NSC frequency in a given cell population under clonal conditions. The protocol begins with the seeding of the cells at a density that allows for the generation of clonal neurospheres. The neurospheres are then transferred to chambered coverslips and differentiated under clonal conditions in conditioned medium, which maximizes the differentiation potential of the neurospheres...
October 4, 2016: Journal of Visualized Experiments: JoVE
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