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https://www.readbyqxmd.com/read/29054697/a-novel-method-for-oxygen-glucose-deprivation-model-in-organotypic-spinal-cord-slices
#1
Jing-Jie Liu, Xiao-Yan Ding, Li Xiang, Feng Zhao, Sheng-Li Huang
This study aimed to establish a model to closely mimic spinal cord hypoxic-ischemic injury with high production and high reproducibility. Fourteen-day cultured organotypic spinal cord slices were divided into 4 groups: control (Ctrl), oxygen glucose deprived for 30min (OGD 30min), OGD 60min, and OGD 120min. The Ctrl slices were incubated with 1ml propidium iodide (PI) solution (5μg/ml) for 30minutes. The OGD groups were incubated with 1ml glucose-free DMEM/F12 medium and 5μl PI solution (1mg/ml) for 30min, 60min and 120min, respectively...
October 17, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29041931/reprogramming-of-stromal-fibroblasts-by-snai2-contributes-to-tumor-desmoplasia-and-ovarian-cancer-progression
#2
Zongyuan Yang, Xin Yang, Sen Xu, Ping Jin, Xiaoting Li, Xiao Wei, Dan Liu, Kecheng Huang, Sixiang Long, Ya Wang, Chaoyang Sun, Gang Chen, Junbo Hu, Li Meng, Ding Ma, Qinglei Gao
BACKGROUND: Molecular profiling in ovarian cancer (OC) revealed that the desmoplasia subtype presented the poorest prognosis, highlighting the contribution of stromal fibroblasts in tumor progression. This study aimed to investigate the molecular characteristics of SNAI2 driving the transcriptional reprogramming of fibroblasts within tumors. METHODS: SNAI2 expression was evaluated in microdissected profiles of various cancers and in various molecular subtypes of OC...
October 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29040322/dexamethasone-mediated-inhibition-of-glioblastoma-neurosphere-dispersal-in-an-ex-vivo-organotypic-neural-assay
#3
Ahmed M Meleis, Aria Mahtabfar, Shabbar Danish, Ramsey A Foty
Glioblastoma is highly aggressive. Early dispersal of the primary tumor renders localized therapy ineffective. Recurrence always occurs and leads to patient death. Prior studies have shown that dispersal of Glioblastoma can be significantly reduced by Dexamethasone (Dex), a drug currently used to control brain tumor related edema. However, due to high doses and significant side effects, treatment is tapered and discontinued as soon as edema has resolved. Prior analyses of the dispersal inhibitory effects of Dex were performed on tissue culture plastic, or polystyrene filters seeded with normal human astrocytes, conditions which inherently differ from the parenchymal architecture of neuronal tissue...
2017: PloS One
https://www.readbyqxmd.com/read/29039467/insulin-like-growth-factor-binding-protein-6-released-from-human-mesenchymal-stem-cells-confers-neuronal-protection-through-igf-1r-mediated-signaling
#4
Hyo-Jin Jeon, Jihye Park, Joo-Hyun Shin, Mi-Sook Chang
Human bone marrow‑derived mesenchymal stem cells (hMSCs) are a desirable cell source for cell‑based therapy to treat nervous system injuries due to their ability to differentiate into specific cell types. In addition to their multipotency, hMSCs render the tissue microenvironment more favorable for tissue repair by secreting various growth factors. Our previous study demonstrated that hMSCs secrete several growth factors, including several insulin‑like growth factor binding proteins (IGFBPs). Among these, IGFBP‑6 binds with high affinity and inhibits insulin growth factor‑2 (IGF‑2) to inhibit the growth of IGF‑2‑dependent tumors...
October 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29030981/mesalazine-treatment-in-organotypic-culture-of-celiac-patients-comparative-study-with-gluten-free-diet
#5
EDITORIAL
Benedetti E, A Viscido, V Castelli, C Maggiani, M d'Angelo, E Di Giacomo, A Antonosante, A Picarelli, G Frieri
Given the central role of gluten in the pathogenesis of celiac disease (CD), a strict gluten-free diet (GFD) is the only validated treatment able to restore epithelium integrity and eliminate risks of complications. The risk of gluten contamination and the persistence of inflammation, even in patients strictly adhering to GFD, may render this treatment not always effective claiming the necessity of different new solutions. Oxidative and nitrosative stress have been indicated to play a pathophysiological role in CD...
October 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29024033/impact-of-x-irradiation-on-microglia
#6
Franziska Menzel, Nicole Kaiser, Susann Haehnel, Felicitas Rapp, Ina Patties, Nina Schöneberg, Zhana Haimon, Kerstin Immig, Ingo Bechmann
Irradiation is widely used to treat brain tumors, and also to create bone marrow (BM) chimeras. BM chimeras are widely used to dissect functions and origin of microglia and blood-derived mononuclear cells under homeostatic or pathological conditions. This is facilitated by the fact that microglia survive irradiation and are thus regarded radio-resistant. In this study, we tested whether microglia are indeed radio-resistant and looked for potential mechanisms that might explain this phenomenon. We analyzed the radio-resistance of microglia independently of their physiological brain environment compared to other mononuclear cells from spleen and brain after X-irradiation with 7 Gy or 30 Gy...
October 10, 2017: Glia
https://www.readbyqxmd.com/read/29018324/design-and-characterization-of-a-human-monoclonal-antibody-that-modulates-mutant-connexin-26-hemichannels-implicated-in-deafness-and-skin-disorders
#7
Liang Xu, Andrea Carrer, Francesco Zonta, Zhihu Qu, Peixiang Ma, Sheng Li, Federico Ceriani, Damiano Buratto, Giulia Crispino, Veronica Zorzi, Gaia Ziraldo, Francesca Bruno, Chiara Nardin, Chiara Peres, Flavia Mazzarda, Anna M Salvatore, Marcello Raspa, Ferdinando Scavizzi, Youjun Chu, Sichun Xie, Xuemei Yang, Jun Liao, Xiao Liu, Wei Wang, Shanshan Wang, Guang Yang, Richard A Lerner, Fabio Mammano
Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26), a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28994300/in-vitro-models-as-a-platform-to-investigate-traumatic-brain-injury
#8
REVIEW
Ashwin Kumaria
Traumatic Brain Injury (TBI) remains a significant cause of mortality and morbidity, affecting individuals of all age groups. Much remains to be learned about its complex pathophysiology, with a view to designing effective neuroprotective strategies to protect sublethally injured brain tissue that would otherwise die in secondary injury processes. Experimental in vivo models offer the potential to study TBI in the laboratory, however, treatments that were neuroprotective in animals have, thus far, largely failed to translate in human clinical studies...
September 2017: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28990726/multiple-mechanisms-of-dimethyl-fumarate-in-amyloid-%C3%AE-induced-neurotoxicity-in-human-neuronal-cells
#9
Michela Campolo, Giovanna Casili, Marika Lanza, Alessia Filippone, Irene Paterniti, Salvatore Cuzzocrea, Emanuela Esposito
Alzheimer disease (AD) is characterized by a complex heterogeneity of pathological changes, and any therapeutic approach categorically requires a multi-targeted way. It has been demonstrated that together with the hallmarks of the disease such as neurofibrillary tangles and senile plaques, oxidative and inflammatory stress covered an important role. Dimethyl fumarate (DMF) is an orally bioavailable methyl ester of fumaric acid and activator of Nrf2 with potential neuroprotective and immunomodulating activities...
October 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28980419/organotypic-brain-explant-culture-as-a-drug-evaluation-system-for-malignant-brain-tumors
#10
Noriaki Minami, Yusuke Maeda, Shunsuke Shibao, Yoshimi Arima, Fumiharu Ohka, Yutaka Kondo, Koji Maruyama, Masatoshi Kusuhara, Takashi Sasayama, Eiji Kohmura, Hideyuki Saya, Oltea Sampetrean
Therapeutic options for malignant brain tumors are limited, with new drugs being continuously evaluated. Organotypic brain slice culture has been adopted for neuroscience studies as a system that preserves brain architecture, cellular function, and the vascular network. However, the suitability of brain explants for anticancer drug evaluation has been unclear. We here adopted a mouse model of malignant glioma based on expression of H-Ras(V12) in Ink4a/Arf(-/-) neural stem/progenitor cells to establish tumor-bearing brain explants from adult mice...
October 4, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28966120/an-rnai-screen-reveals-an-essential-role-for-hipk4-in-human-skin-epithelial-differentiation-from-ipscs
#11
Lionel Larribère, Marta Galach, Daniel Novak, Karla Arévalo, Hans Christian Volz, Hans-Jürgen Stark, Petra Boukamp, Michael Boutros, Jochen Utikal
Molecular mechanisms responsible for the development of human skin epithelial cells are incompletely understood. As a consequence, the efficiency to establish a pure skin epithelial cell population from human induced pluripotent stem cells (hiPSCs) remains poor. Using an approach including RNAi and high-throughput imaging of early epithelial cells, we identified candidate kinases involved in their differentiation from hiPSCs. Among these, we found HIPK4 to be an important inhibitor of this process. Indeed, its silencing increased the amount of generated skin epithelial precursors at an early time point, increased the amount of generated keratinocytes at a later time point, and improved growth and differentiation of organotypic cultures, allowing for the formation of a denser basal layer and stratification with the expression of several keratins...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28963609/overexpression-of-timp-1-and-sensitivity-to-topoisomerase-inhibitors-in-glioblastoma-cell-lines
#12
Charlotte Aaberg-Jessen, Louise Fogh, Mia Dahl Sørensen, Bo Halle, Nils Brünner, Bjarne Winther Kristensen
The multifunctional protein - tissue inhibitor of metalloproteinases-1 (TIMP-1) - has been associated with a poor prognosis in several types of cancers including glioblastomas. In addition, TIMP-1 has been associated with decreased response to chemotherapy, and especially the efficacy of the family of topoisomerase (TOP) inhibitors has been related to TIMP-1. As a second line treatment of glioblastomas, the vascular endothelial growth factor (VEGF) antibody bevacizumab is administered in combination with the TOP1 inhibitor irinotecan and glioblastoma cell levels of TIMP-1 could therefore potentially influence the efficacy of such treatment...
September 30, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28962665/direct-conversion-of-human-fibroblasts-to-functional-excitatory-cortical-neurons-integrating-into-human-neural-networks
#13
Giedre Miskinyte, Karthikeyan Devaraju, Marita Grønning Hansen, Emanuela Monni, Daniel Tornero, Niels Bjarne Woods, Johan Bengzon, Henrik Ahlenius, Olle Lindvall, Zaal Kokaia
BACKGROUND: Human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated. METHODS: Here we screened for transcription factor combinations that could potentially convert human fibroblasts to functional excitatory cortical neurons. The induced cortical (iCtx) cells were analyzed for cortical neuronal identity using immunocytochemistry, single-cell quantitative polymerase chain reaction (qPCR), electrophysiology, and their ability to integrate into human neural networks in vitro and ex vivo using electrophysiology and rabies virus tracing...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28962037/assessment-of-sperm-nuclear-quality-after-in-vitro-maturation-of-fresh-or-frozen-thawed-mouse-pre-pubertal-testes
#14
A Oblette, N Rives, L Dumont, A Rives, F Verhaeghe, F Jumeau, C Rondanino
STUDY QUESTION: Is nuclear quality of in vitro generated spermatozoa from fresh or frozen/thawed pre-pubertal mouse testes similar to that of their in vivo counterparts? SUMMARY ANSWER: The production of spermatozoa with aneuploidy, DNA fragmentation or chromatin condensation defects was not significantly increased in organotypic cultures compared to in vivo controls. WHAT IS KNOWN ALREADY: Although murine spermatozoa have been produced in vitro from pre-pubertal testes, their nuclear DNA integrity has never been investigated...
August 23, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28947761/human-cerebrospinal-fluid-promotes-long-term-neuronal-viability-and-network-function-in-human-neocortical-organotypic-brain-slice-cultures
#15
Niklas Schwarz, Ulrike B S Hedrich, Hannah Schwarz, Harshad P A, Nele Dammeier, Eva Auffenberg, Francesco Bedogni, Jürgen B Honegger, Holger Lerche, Thomas V Wuttke, Henner Koch
Pathophysiological investigation of CNS-related diseases, such as epilepsy or neurodegenerative disorders, largely relies on histological studies on human post mortem tissue, tissue obtained by biopsy or resective surgery and on studies using disease models including animal models, heterologous expression systems or cell culture based approaches. However, in general it remains elusive to what extent results obtained in model systems can be directly translated to the human brain, calling for strategies allowing validation or even primary investigation in live human CNS tissue...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28946193/anticonvulsant-activity-organotypic-hippocampal-neuroprotection-assay-and-in-silico-sodium-channel-blocking-potential-of-2-amino-6-nitrobenzothiazole-derived-semicarbazones
#16
Rati Kailash Prasad Tripathi, Senthil Raja Ayyannan
Epilepsy is one of the dreadful neurodegenerative disorder characterized by recurrent, unprovoked seizures. Currently available antiepileptic drugs are still associated with enormous side effects resulting in search of newer, more effective and safer agents. In view of this, we have investigated anticonvulsant activity of 2-amino-6-nitrobenzothiazole derived semicarbazones (7-32) in various in-vivo animal seizure models viz. maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and 6Hz psychomotor seizure model...
September 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28941572/effects-of-neural-stem-cell-media-on-hypoxic-injury-in-rat-hippocampal-slice-cultures
#17
Na Mi Lee, Soo Ahn Chae, Hong Jun Lee
Neonatal hypoxic-ischemic brain injuries cause serious neurological sequelae, yet there is currently no effective treatment for them. We hypothesized that neurotrophic factors released into the medium by stem cells could supply hypoxia-damaged organotypic hippocampal slice cultures with regenerative abilities. We prepared organotypic slice cultures of the hippocampus of 7-day-old Sprague-Dawley rats based on the modified Stoppini method; slices were cultured for 14days in vitro using either Gahwiler's medium (G-medium) or stem cell-conditioned medium (S-medium) as culture medium...
December 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28940556/lllt-effects-on-oral-keratinocytes-in-an-organotypic-3d-model
#18
Fernanda G Basso, Taisa N Pansani, Diana G Soares, Josimeri Hebling, Carlos Alberto de Souza Costa
Several in vitro studies evaluated the cellular and molecular events related to interactions between phototherapy and target tissues, including oral keratinocytes and fibroblasts, providing elucidative data about phototherapy-induced healing. However, these interactions were limited to the application of a bidimensional cell culture model of oral mucosal cells. Thus, the present study evaluated the use of an organotypic oral epithelium model to elucidate the morphological and phenotypic responses of cells subjected to low-level laser therapy (LLLT)...
September 23, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28940194/a-new-model-system-identifies-egfr-her2-and-her2-her3-heterodimers-as-potent-inducers-of-oesophageal-epithelial-cell-invasion
#19
Christiane Daniela Fichter, Camilla Maria Przypadlo, Achim Buck, Nicola Herbener, Bianca Riedel, Luisa Schäfer, Hiroshi Nakagawa, Axel Walch, Thomas Reinheckel, Martin Werner, Silke Lassmann
Oesophageal squamous cell carcinomas and oesophageal adenocarcinomas display distinct patterns of ErbB expression and dimers. The functional effects of specific ErbB homo- or heterodimers on oesophageal (cancer) cell behaviour, particularly invasion of early carcinogenesis remains unknown. Here, a new cellular model system for controlled activation of EGFR or HER2 and EGFR/HER2 or HER2/HER3 homo- and heterodimers was studied in non-neoplastic squamous oesophageal epithelial Het-1A cells. EGFR, HER2 and HER3 intracellular domains (ICDs) were fused to dimerization domains (DmrA / DmrA and DmrC), and transduced into Het-1A cells lacking ErbB expression...
September 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28926987/the-impact-of-non-lethal-single-dose-radiation-on-tumor-invasion-and-cytoskeletal-properties
#20
Tim Hohmann, Urszula Grabiec, Carolin Vogel, Chalid Ghadban, Stephan Ensminger, Matthias Bache, Dirk Vordermark, Faramarz Dehghani
Irradiation is the standard therapy for glioblastoma multiforme. Glioblastoma are highly resistant to radiotherapy and the underlying mechanisms remain unclear. To better understand the biological effects of irradiation on glioblastoma cells, we tested whether nonlethal irradiation influences the invasiveness, cell stiffness, and actin cytoskeleton properties. Two different glioblastoma cell lines were irradiated with 2 Gy and changes in mechanical and migratory properties and alterations in the actin structure were measured...
September 18, 2017: International Journal of Molecular Sciences
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