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https://www.readbyqxmd.com/read/27905992/variable-sensitivity-to-complement-dependent-cytotoxicity-in-murine-models-of-neuromyelitis-optica
#1
Yiting Liu, Danielle E Harlow, Katherine S Given, Gregory P Owens, Wendy B Macklin, Jeffrey L Bennett
BACKGROUND: Studies of neuromyelitis optica (NMO), an autoimmune disease of the central nervous system (CNS), have demonstrated that autoantibodies against the water channel aquaporin-4 (AQP4) induce astrocyte damage through complement-dependent cytotoxicity (CDC). In developing experimental models of NMO using cells, tissues or animals from mice, co-administration of AQP4-IgG and normal human serum, which serves as the source of human complement (HC), is required. The sensitivity of mouse CNS cells to HC and CDC in these models is not known...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27896917/on-the-pathogenesis-of-mtor-associated-stomatitis-mias-studies-using-an-organotypic-model-of-the-oral-mucosa
#2
Stephen Sonis, Paulette Wright Andreotta, Gregory Lyng
OBJECTIVE: mTOR inhibitor treatment of solid cancers is associated with mTOR inhibitor-associated stomatitis (mIAS) a common, significant, dose-limiting toxicity, with aphthous-like lesions. Our objective was to assess the utility of a new organotypic model in defining mIAS' pathogenesis. MATERIALS AND METHODS: The effect of everolimus on organotypic human oral mucosa was studied. Sterile specimens were assessed 24 hr and 48 hr after exposure to varying concentrations of everolimus...
November 29, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27878736/in-vitro-cyto-biocompatibility-study-of-thin-film-transistors-substrates-using-an-organotypic-culture-method
#3
Eric Leclerc, Jean-Luc Duval, Christophe Egles, Satoshi Ihida, Hiroshi Toshiyoshi, Agnès Tixier-Mita
Thin-Film-Transistors Liquid-Crystal Display has become a standard in the field of displays. However, the structure of these devices presents interest not only in that field, but also for biomedical applications. One of the key components, called here TFT substrate, is a glass substrate with a dense and large array of thousands of transparent micro-electrodes that can be considered as a large scale multi-electrode array(s). Multi-electrode array(s) are widely used for in vitro electrical investigations on neurons and brain, allowing excitation, registration, and recording of their activity...
January 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/27873267/generation-and-infection-of-organotypic-cultures-with-epstein-barr-virus
#4
Rachel M Temple, Craig Meyers, Clare E Sample
While numerous model systems are available to study EBV latency in B cells and have contributed greatly to our understanding of the role of these cells in the viral life cycle, models to study the EBV life cycle in epithelial cells in vitro are lacking. Epithelial cells are poorly infected in vitro, and EBV-infected cell lines have not been successfully obtained from epithelial tumors. Recently, we have demonstrated that organotypic cultures of oral keratinocytes can be used as a model to study EBV infection in the epithelial tissue...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27871963/uptake-of-silica-nanoparticles-in-the-brain-and-effects-on-neuronal-differentiation-using-different-in-vitro-models
#5
A D Ducray, A Stojiljkovic, A Möller, M H Stoffel, H R Widmer, M Frenz, M Mevissen
Nanomedicine offers a promising tool for therapies of brain diseases, but they may be associated with potential adverse effects. The aim of this study was to investigate the uptake of silica-nanoparticles engineered for laser-tissue soldering in the brain using SH-SY5Y cells, dissociated and organotypic slice cultures from rat hippocampus. Nanoparticles were predominantly taken up by microglial cells in the hippocampal cultures but nanoparticles were also found in differentiated SH-SY5Y cells. The uptake was time- and concentration-dependent in primary hippocampal cells...
November 19, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27867665/dose-dependent-differential-effect-of-neurotrophic-factors-on-in-vitro-and-in-vivo-regeneration-of-motor-and-sensory-neurons
#6
Daniel Santos, Francisco Gonzalez-Perez, Xavier Navarro, Jaume Del Valle
Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27865774/a-systems-toxicology-approach-for-comparative-assessment-biological-impact-of-an-aerosol-from-a-candidate-modified-risk-tobacco-product-and-cigarette-smoke-on-human-organotypic-bronchial-epithelial-cultures
#7
Anita R Iskandar, Carole Mathis, Walter K Schlage, Stefan Frentzel, Patrice Leroy, Yang Xiang, Alain Sewer, Shoaib Majeed, Laura Ortega-Torres, Stephanie Johne, Emmanuel Guedj, Keyur Trivedi, Gilles Kratzer, Celine Merg, Ashraf Elamin, Florian Martin, Nikolai V Ivanov, Manuel C Peitsch, Julia Hoeng
This study reports a comparative assessment of the biological impact of a heated tobacco aerosol from the tobacco heating system (THS) 2.2 and smoke from a combustible 3R4F cigarette. Human organotypic bronchial epithelial cultures were exposed to an aerosol from THS2.2 (a candidate modified-risk tobacco product) or 3R4F smoke at similar nicotine concentrations. A systems toxicology approach was applied to enable a comprehensive exposure impact assessment. Culture histology, cytotoxicity, secreted pro-inflammatory mediators, ciliary beating, and genome-wide mRNA/miRNA profiles were assessed at various time points post-exposure...
November 16, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27865053/neural-progenitor-cells-and-their-role-in-the-development-and-evolutionary-expansion-of-the-neocortex
#8
REVIEW
Takashi Namba, Wieland B Huttner
The evolutionary expansion of the mammalian brain, notably the neocortex, provides a platform for the higher cognitive abilities that characterize humans. Cortical expansion is accompanied by increased folding of the pial surface, which gives rise to a gyrencephalic (folded) rather than lissencephalic (unfolded) neocortex. This expansion reflects the prolonged and increased proliferation of neural stem and progenitor cells (NPCs). Distinct classes of NPCs can be distinguished based on either cell biological criteria (apical progenitors [APs], basal progenitors [BPs]) or lineage (primary progenitors and secondary progenitors)...
November 16, 2016: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/27864382/molecular-dynamics-of-dkk4-modulates-wnt-action-and-regulates-meibomian-gland-development
#9
Jian Sima, Yulan Piao, Yaohui Chen, David Schlessinger
Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, similar to that observed in Eda-ablated Tabby mice...
November 18, 2016: Development
https://www.readbyqxmd.com/read/27864052/tumor-tissue-slice-cultures-as-a-platform-for-analyzing-tissue-penetration-and-biological-activities-of-nanoparticles
#10
Lea Merz, Sabrina Höbel, Sonja Kallendrusch, Alexander Ewe, Ingo Bechmann, Heike Franke, Felicitas Merz, Achim Aigner
The success of therapeutic nanoparticles depends, among others, on their ability to penetrate a tissue for actually reaching the target cells, and their efficient cellular uptake in the context of intact tissue and stroma. Various nanoparticle modifications have been implemented for altering physicochemical and biological properties. Their analysis, however, so far mainly relies on cell culture experiments which only poorly reflect the in vivo situation, or is based on in vivo experiments that are often complicated by whole-body pharmacokinetics and are rather tedious especially when analyzing larger nanoparticle sets...
November 15, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27846345/systems-biology-for-organotypic-cell-cultures
#11
Sonia Grego, Edward R Dougherty, Francis J Alexander, Scott S Auerbach, Brian R Berridge, Michael L Bittner, Warren Casey, Philip C Cooley, Ajit Dash, Stephen S Ferguson, Timothy R Fennell, Brian T Hawkins, Anthony J Hickey, Andre Kleensang, Michael N J Liebman, Florian Martin, Elizabeth A Maull, Jason Paragas, Guilin Gary Qiao, Sreenivasa Ramaiahgari, Susan J Sumner, Miyoung Yoon
Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, "organotypic" cell cultures, which mimic functional responses of living tissue...
November 14, 2016: ALTEX
https://www.readbyqxmd.com/read/27844029/dose-dependent-inhibition-of-demyelination-and-microglia-activation-by-ivig
#12
Meike Winter, Christine Baksmeier, Julia Steckel, Sumanta Barman, Manish Malviya, Melanie Harrer-Kuster, Hans-Peter Hartung, Norbert Goebels
OBJECTIVE: Intravenous immunoglobulin (IVIG) is an established treatment for numerous autoimmune conditions. Clinical trials of IVIG for multiple sclerosis, using diverse dose regimens, yielded controversial results. The aim of this study is to dissect IVIG effector mechanisms on demyelination in an ex vivo model of the central nervous system (CNS)-immune interface. METHODS: Using organotypic cerebellar slice cultures (OSC) from transgenic mice expressing green fluorescent protein (GFP) in oligodendrocytes/myelin, we induced extensive immune-mediated demyelination and oligodendrocyte loss with an antibody specific for myelin oligodendrocyte glycoprotein (MOG) and complement...
November 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27837212/-preclinical-models-in-head-and-neck-tumors-evaluation-of-cellular-and-molecular-resistance-mechanisms-in-the-tumor-microenvironment
#13
A Affolter, J Hess
Because head and neck squamous cell carcinomas (HNSCC) are characterized by a distinct intertumorigenic and intratumorigenic heterogeneity, they often show substantial differences in the response to established therapy strategies. At present, a multitude of biologics and new pharmacological compounds for targeted therapies are available that allow more efficient and less toxic treatment. There is increasing pressure to establish predictive assays not only for ex ante analysis of the individual patient response to combined chemoradiotherapy and targeted therapies but also for investigation of the efficacy of new drugs...
December 2016: HNO
https://www.readbyqxmd.com/read/27830712/a-dynamic-in-vivo-like-organotypic-blood-brain-barrier-model-to-probe-metastatic-brain-tumors
#14
Hui Xu, Zhongyu Li, Yue Yu, Saman Sizdahkhani, Winson S Ho, Fangchao Yin, Li Wang, Guoli Zhu, Min Zhang, Lei Jiang, Zhengping Zhuang, Jianhua Qin
The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27829391/esophageal-squamous-cell-carcinoma-invasion-is-inhibited-by-activin-a-in-acvrib-positive-cells
#15
Holli A Loomans, Shanna A Arnold, Laura L Quast, Claudia D Andl
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a global public health issue, as it is the eighth most common cancer worldwide. The mechanisms behind ESCC invasion and progression are still poorly understood, and warrant further investigation into these processes and their drivers. In recent years, the ligand Activin A has been implicated as a player in the progression of a number of cancers. The objective of this study was to investigate the role of Activin A signaling in ESCC...
November 9, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27826417/desflurane-impairs-outcome-of-organotypic-hippocampal-slices-in-an-in-vitro-model-of-traumatic-brain-injury
#16
Matthias Krings, Anke Höllig, Jingjin Liu, Linda Grüsser, Rolf Rossaint, Mark Coburn
Decreased mortality and disability after traumatic brain injury is a significant medical challenge. Desflurane, a widely used volatile anesthetic has proven to be neuroprotective in a variety of in vitro and in vivo models of ischemic brain injury. The aim of this study was to investigate whether desflurane exhibits neuroprotective properties in an in vitro model of traumatic brain injury. Organotypic hippocampal slice cultures were prepared from brains of 5-7-day-old C57/BL6 mouse pups. After 14 days of culture, the slices were subjected to a focal mechanical trauma and thereafter incubated with three different concentrations of desflurane (2, 4 and 6%) for 2, 24 and 72 hours...
March 2016: Medical Gas Research
https://www.readbyqxmd.com/read/27825148/creating-interactions-between-tissue-engineered-skeletal-muscle-and-the-peripheral-nervous-system
#17
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/27824929/tissue-kallikrein-inhibitors-based-on-the-sunflower-trypsin-inhibitor-scaffold-a-potential-therapeutic-intervention-for-skin-diseases
#18
Wenjie Chen, Veronica A Kinsler, Derek Macmillan, Wei-Li Di
Tissue kallikreins (KLKs), in particular KLK5, 7 and 14 are the major serine proteases in the skin responsible for skin shedding and activation of inflammatory cell signaling. In the normal skin, their activities are controlled by an endogenous protein protease inhibitor encoded by the SPINK5 gene. Loss-of-function mutations in SPINK5 leads to enhanced skin kallikrein activities and cause the skin disease Netherton Syndrome (NS). We have been developing inhibitors based on the Sunflower Trypsin Inhibitor 1 (SFTI-1) scaffold, a 14 amino acids head-to-tail bicyclic peptide with a disulfide bond...
2016: PloS One
https://www.readbyqxmd.com/read/27821307/in%C3%A2-vitro-activation-of-the-neuro-transduction-mechanism-in-sensitive-organotypic-human-skin-model
#19
Francesca Martorina, Costantino Casale, Francesco Urciuolo, Paolo A Netti, Giorgia Imparato
Recent advances in tissue engineering have encouraged researchers to endeavor the production of fully functional three-dimensional (3D) thick human tissues in vitro. Here, we report the fabrication of a fully innervated human skin tissue in vitro that recapitulates and replicates skin sensory function. Previous attempts to innervate in vitro 3D skin models did not demonstrate an effective functionality of the nerve network. In our approach, we initially engineer functional human skin tissue based on fibroblast-generated dermis and differentiated epidermis; then, we promote rat dorsal root ganglion (DRG) neurons axon ingrowth in the de-novo developed tissue...
January 2017: Biomaterials
https://www.readbyqxmd.com/read/27818162/identification-of-axon-growth-promoters-in-the-secretome-of-the-deer-antler-velvet
#20
Wolfgang Pita-Thomas, Gemma Barroso-García, Veronica Moral, Amber R Hackett, Valeria Cavalli, Manuel Nieto-Diaz
Every spring, deer cast their old antlers and initiate a regeneration process, which yields a new set of antlers of up to 1m in length. Over the course of three months, branches of the trigeminal nerve, originating from the frontal skull, innervate velvet, a modified skin that covers the regenerating antler. The rate of growth of these axons reaches up to 2cm per day making them the fastest regenerating axons in adult mammals. Here, we aim to identify the factors secreted by velvet that promote such high speed axon growth...
November 4, 2016: Neuroscience
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