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https://www.readbyqxmd.com/read/28723673/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#1
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28713615/effects-of-radiofrequency-exposure-emitted-from-a-gsm-mobile-phone-on-proliferation-differentiation-and-apoptosis-of-neural-stem-cells
#2
Mahsa Eghlidospour, Amir Ghanbari, Seyyed Mohammad Javad Mortazavi, Hassan Azari
Due to the importance of neural stem cells (NSCs) in plasticity of the nervous system and treating neurodegenerative diseases, the main goal of this study was to evaluate the effects of radiofrequency radiation emitted from a GSM 900-MHz mobile phone with different exposure duration on proliferation, differentiation and apoptosis of adult murine NSCs in vitro. We used neurosphere assay to evaluate NSCs proliferation, and immunofluorescence assay of neural cell markers to examine NSCs differentiation. We also employed alamarBlue and caspase 3 apoptosis assays to assess harmful effects of mobile phone on NSCs...
June 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28706205/the-alkaloids-of-banisteriopsis-caapi-the-plant-source-of-the-amazonian-hallucinogen-ayahuasca-stimulate-adult-neurogenesis-in-vitro
#3
Jose A Morales-García, Mario de la Fuente Revenga, Sandra Alonso-Gil, María Isabel Rodríguez-Franco, Amanda Feilding, Ana Perez-Castillo, Jordi Riba
Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697342/tumor-evolution-of-glioma-intrinsic-gene-expression-subtypes-associates-with-immunological-changes-in-the-microenvironment
#4
Qianghu Wang, Baoli Hu, Xin Hu, Hoon Kim, Massimo Squatrito, Lisa Scarpace, Ana C deCarvalho, Sali Lyu, Pengping Li, Yan Li, Floris Barthel, Hee Jin Cho, Yu-Hsi Lin, Nikunj Satani, Emmanuel Martinez-Ledesma, Siyuan Zheng, Edward Chang, Charles-Etienne Gabriel Sauvé, Adriana Olar, Zheng D Lan, Gaetano Finocchiaro, Joanna J Phillips, Mitchel S Berger, Konrad R Gabrusiewicz, Guocan Wang, Eskil Eskilsson, Jian Hu, Tom Mikkelsen, Ronald A DePinho, Florian Muller, Amy B Heimberger, Erik P Sulman, Do-Hyun Nam, Roel G W Verhaak
We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single-cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4(+) T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28694236/fibrin-functionalization-with-synthetic-adhesive-ligands-interacting-with-%C3%AE-6%C3%AE-1-integrin-receptor-enhance-neurite-outgrowth-of-embryonic-stem-cell-derived-neural-stem-progenitors
#5
Joana Silva, Ana R Bento, Daniela Barros, Tiago L Laundos, Susana R Sousa, Pedro Quelhas, Mónica M Sousa, Ana P Pêgo, Isabel F Amaral
To enhance fibrin hydrogel affinity towards pluripotent stem cell-derived neural stem/progenitor cells (NSPCs) and its capacity to support NSPC migration and neurite extension, we explored the tethering of synthetic peptides engaging integrin α6β1, a cell receptor enriched in NSPCs. Six α6β1 integrin ligands were tested for their ability to support integrin α6β1-mediated adhesion of embryonic stem cell-derived NSPCs (ES-NSPs) and sustain ES-NSPC viability, migration, and neuronal differentiation. Due to their better performance, peptides T1, HYD1, and A5G81 were immobilized into fibrin and functionalized gels characterized in terms of peptide binding efficiency, structure and viscoelastic properties...
July 7, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28691701/instructing-cells-with-programmable-peptide-dna-hybrids
#6
Ronit Freeman, Nicholas Stephanopoulos, Zaida Álvarez, Jacob A Lewis, Shantanu Sur, Chris M Serrano, Job Boekhoven, Sungsoo S Lee, Samuel I Stupp
The native extracellular matrix is a space in which signals can be displayed dynamically and reversibly, positioned with nanoscale precision, and combined synergistically to control cell function. Here we describe a molecular system that can be programmed to control these three characteristics. In this approach we immobilize peptide-DNA (P-DNA) molecules on a surface through complementary DNA tethers directing cells to adhere and spread reversibly over multiple cycles. The DNA can also serve as a molecular ruler to control the distance-dependent synergy between two peptides...
July 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28690640/wdr62-regulates-early-neural-and-glial-progenitor-specification-of-human-pluripotent-stem-cells
#7
Abdullah J Alshawaf, Ana Antonic, Efstratios Skafidas, Dominic Chi-Hung Ng, Mirella Dottori
Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28687190/a-synthetic-bmp-2-mimicking-peptide-induces-glioblastoma-stem-cell-differentiation
#8
Elena Rampazzo, Monica Dettin, Francesca Maule, Alessandra Scabello, Luisa Calvanese, Gabriella D'Auria, Lucia Falcigno, Elena Porcù, Annj Zamuner, Alessandro Della Puppa, Daniele Boso, Giuseppe Basso, Luca Persano
BACKGROUND: Glioblastoma (GBM) is the most aggressive type of primary brain tumor, characterized by the intrinsic resistance to chemotherapy due to the presence of a highly aggressive Cancer Stem Cell (CSC) sub-population. In this context, Bone Morphogenetic Proteins (BMPs) have been demonstrated to induce CSC differentiation and to sensitize GBM cells to treatments. METHODS: The BMP-2 mimicking peptide, named GBMP1a, was synthesized on solid-phase by Fmoc chemistry...
July 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28683812/mechano-growth-factor-a-splice-variant-of-igf-1-promotes-neurogenesis-in-the-aging-mouse-brain
#9
Jason J Tang, Jewel L Podratz, Miranda Lange, Heidi J Scrable, Mi-Hyeon Jang, Anthony J Windebank
Mechano growth factor (MGF) is a splice variant of IGF-1 first described in skeletal muscle. MGF induces muscle cell proliferation in response to muscle stress and injury. In control mice we found endogenous expression of MGF in neurogenic areas of the brain and these levels declined with age. To better understand the role of MGF in the brain, we used transgenic mice that constitutively overexpressed MGF from birth. MGF overexpression significantly increased the number of BrdU+ proliferative cells in the dentate gyrus (DG) of the hippocampus and subventricular zone (SVG)...
July 7, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28674801/high-efficiency-transfection-of-glioblastoma-cells-and-a-simple-spheroid-migration-assay
#10
Carsten Hagemann, Diana Amend, Almuth F Kessler, Thomas Linsenmann, Ralf-Ingo Ernestus, Mario Löhr
Despite international research efforts, patients with glioblastoma multiforme (GBM)-the most common malignant brain tumors in adults-exhibit a very unfavorable prognosis. Their aggressive local growth pattern and increased invasiveness, due to a high motility of the tumor cells, hamper treatment. However, the molecular mechanisms regulating glioblastoma cell migration are still elusive. Here, we describe the combination of a highly efficient cell transfection by Nucleofection(®) technology and the generation of spheroids from these transfected glioblastoma cell lines...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28674431/9-cis-retinoic-acid-induces-neurorepair-in-stroke-brain
#11
Seong-Jin Yu, Mikko Airavaara, Kuo-Jen Wu, Brandon K Harvey, H S Liu, Yihong Yang, Alex Zacharek, Jieli Chen, Yun Wang
The purpose of this study was to examine the neurorestorative effect of delayed 9 cis retinoic acid (9cRA) treatment for stroke. Adult male rats received a 90-min right distal middle cerebral artery occlusion (dMCAo). Animals were separated into two groups with similar infarction sizes, based on magnetic resonance imaging on day 2 after dMCAo. 9cRA or vehicle was given via an intranasal route daily starting from day 3. Stroke rats receiving 9cRA post-treatment showed an increase in brain 9cRA levels and greater recovery in motor function...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28669622/smad4-is-essential-for-directional-progression-from-committed-neural-progenitor-cells-through-neuronal-differentiation-in-the-postnatal-mouse-brain
#12
Motoko Kawaguchi-Niida, Noriyuki Shibata, Yasuhide Furuta
Signaling by the TGFβ super-family, consisting of TGFβ/activin- and bone morphogenetic protein (BMP) branch pathways, is involved in the central nervous system patterning, growth, and differentiation during embryogenesis. Neural progenitor cells are implicated in various pathological conditions, such as brain injury, infarction, Parkinson's disease and Alzheimer's disease. However, the roles of TGFβ/BMP signaling in the postnatal neural progenitor cells in the brain are still poorly understood. We examined the functional contribution of Smad4, a key integrator of TGFβ/BMP signaling pathways, to the regulation of neural progenitor cells in the subventricular zone (SVZ)...
June 29, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28667908/transcription-factor-nrf2-controls-the-fate-of-neural-stem-cells-in-the-subgranular-zone-of-the-hippocampus
#13
Natalia Robledinos-Antón, Ana I Rojo, Elisabete Ferreiro, Ángel Núñez, Karl-Heinz Krause, Vincent Jaquet, Antonio Cuadrado
Neural stem/progenitor cells (NSPCs) located at the subgranular zone (SGZ) of the hippocampus participate in the maintenance of synaptic networks that ensure cognitive functions during life. Although it is known that this neurogenic niche losses activity with oxidative stress and ageing, the molecular events involved in its regulation are largely unknown. Here, we studied the role of transcription factor Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) in the control of NSPCs destinies in the SGZ. We first describe that NRF2-knockout (Nrf2(-/-)) mice exhibit impaired long term potentiation, a function that requires integrity of the SGZ, therefore suggesting a cognitive deficit that might be linked to hippocampal neurogenesis...
June 27, 2017: Redox Biology
https://www.readbyqxmd.com/read/28666838/mmp-2-a-modulator-of-neuronal-precursor-activity-and-cognitive-and-motor-behaviors
#14
Qi Li, Michael Michaud, Ravi Shankar, Sandra Canosa, Michael Schwartz, Joseph A Madri
Matrix Metalloproteinase2, (MMP2, gelatinase A) is a zinc-containing enzyme with a broad substrate specificity including components of the extracellular matrix, cell surface molecules and a wide range bioactive molecules. MMP2 is known to play important roles in a variety of signaling pathways and processes in a wide range of cell types and tissues. In this report we elucidate the effects of the absence of MMP2 in Neural Precursor Cells (NPC) derived from C57BL/6 MMP2 KO mice and in primary and secondary neurosphere formation...
June 27, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28663132/developmental-neurogenesis-in-mouse-and-xenopus-is-impaired-in-the-absence-of-nosip
#15
Meike Hoffmeister, Julia Krieg, Alexander Ehrke, Franziska A Seigfried, Lisa Wischmann, Petra Dietmann, Susanne J Kühl, Stefanie Oess
BACKGROUND: Genetic deletion of Nosip in mice causes holoprosencephaly, however, the function of Nosip in neurogenesis is currently unknown. RESULTS: We combined two vertebrate model organisms, the mouse and the South African clawed frog, Xenopus laevis, to study the function of Nosip in neurogenesis. We found, that size and cortical thickness of the developing brain of Nosip knockout mice were reduced. Accordingly, the formation of postmitotic neurons was greatly diminished, concomitant with a reduced number of apical and basal neural progenitor cells in vivo...
June 27, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28655889/disruption-of-the-monocarboxylate-transporter-4-basigin-interaction-inhibits-the-hypoxic-response-proliferation-and-tumor-progression
#16
Dillon M Voss, Raffaella Spina, David L Carter, Kah Suan Lim, Constance J Jeffery, Eli E Bar
We have previously shown that glioblastoma stem cells (GSCs) are enriched in the hypoxic tumor microenvironment, and that monocarboxylate transporter-4 (MCT4) is critical for mediating GSC signaling in hypoxia. Basigin is involved in many physiological functions during early stages of development and in cancer and is required for functional plasma membrane expression of MCT4. We sought to determine if disruption of the MCT-Basigin interaction may be achieved with a small molecule. Using a cell-based drug-screening assay, we identified Acriflavine (ACF), a small molecule that inhibits the binding between Basigin and MCT4...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28654046/hypoxic-preconditioning-of-marrow-derived-progenitor-cells-as-a-source-for-the-generation-of-mature-schwann-cells
#17
Yat-Ping Tsui, Alan Kwan-Long Mung, Ying-Shing Chan, Daisy Kwok-Yan Shum, Graham Ka-Hon Shea
This manuscript describes a means to enrich for neural progenitors from the marrow stromal cell (MSC) population and thereafter to direct them to the mature Schwann cell fate. We subjected rat and human MSCs to transient hypoxic conditions (1% oxygen for 16 h) followed by expansion as neurospheres upon low-attachment substratum with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) supplementation. Neurospheres were seeded onto poly-D-lysine/laminin-coated tissue culture plastic and cultured in a gliogenic cocktail containing β-Heregulin, bFGF, and platelet-derived growth factor (PDGF) to generate Schwann cell-like cells (SCLCs)...
June 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28649667/impact-of-protein-kinase-ck2-inhibitors-on-proliferation-and-differentiation-of-neural-stem-cells
#18
Melanie Bender, Lisa Schwind, David Grundmann, Monika Martin, Markus Klotz, Claudia Götz, Mathias Montenarh, Karl-Herbert Schäfer
BACKGROUND: Protein kinases play central roles in cell and tissue development. Protein kinase CK2, an ubiquitously expressed serine/threonine kinase has severe impacts on embryo- and spermatogenesis. Since its role in neurogenesis has so far only been investigated in very few studies, we analysed the role of CK2 in neural stem cells by using two specific inhibitors. METHODS: Neural stem cells were isolated from the subventricular zone of neonatal mice, using a neurosphere approach...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28647514/aqueous-cigarette-tar-extracts-disrupt-corticogenesis-from-human-embryonic-stem-cells-in-vitro
#19
Aynun N Begum, Jose S Aguilar, Yiling Hong
BACKGROUND: Cigarette butts are the most common form of litter in the world, and approximately 4.5 trillion smoked cigarettes are discarded every year worldwide. Cigarette butts contain over 4000 chemicals, many of which are known to have neurotoxic effects. Stem cell neuronal differentiation provides an excellent cellular model with which to examine the impact of aqueous cigarette tar extracts (ACTEs) on neurodevelopment. METHODS: We have developed a neurosphere-based stem cell neuronal differentiation protocol that can recapitulate corticogenesis and produce cell types that are similar to upper and lower layer cortical projection neurons found in the germinal zone of the developing human cortex...
June 22, 2017: Environmental Research
https://www.readbyqxmd.com/read/28634469/alexander-disease-mutations-produce-cells-with-coexpression-of-glial-fibrillary-acidic-protein-and-ng2-in-neurosphere-cultures-and-inhibit-differentiation-into-mature-oligodendrocytes
#20
Ulises Gómez-Pinedo, Maria Salomé Sirerol-Piquer, María Durán-Moreno, José Manuel García-Verdugo, Jorge Matias-Guiu
BACKGROUND: Alexander disease (AxD) is a rare disease caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). The disease is characterized by presence of GFAP aggregates in the cytoplasm of astrocytes and loss of myelin. OBJECTIVES: Determine the effect of AxD-related mutations on adult neurogenesis. METHODS: We transfected different types of mutant GFAP into neurospheres using the nucleofection technique. RESULTS: We find that mutations may cause coexpression of GFAP and NG2 in neurosphere cultures, which would inhibit the differentiation of precursors into oligodendrocytes and thus explain the myelin loss occurring in the disease...
2017: Frontiers in Neurology
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