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https://www.readbyqxmd.com/read/28435095/application-of-advanced-preclinical-models-and-methods-in-anesthetic-neurotoxicity-research
#1
REVIEW
Cheng Wang, Xuan Zhang, Fang Liu
Recently, there has been increasing concern regarding the potential of anesthetics to disturb the long-term function of the central nervous system (CNS). The field of anesthesia-related toxicology, therefore, has engaged multiple scientific disciplines and utilized a variety of pre-clinical research models in an attempt to identify the basic characteristics of the anesthetic agents that may produce acute and/or chronic adverse effects on the CNS. This review discusses how the application of advanced research approaches and models, such as the nonhuman primate, neural stem cell-derived organotypic slice cultures and/or organs-on-chips systems, can serve as translational models of infantile anesthetic exposure...
April 20, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28429257/low-molecular-weight-components-of-the-metabolome-control-the-proliferative-activity-in-cellular-and-bacterial-cultures
#2
T Ya Vakhitov, N I Chalisova, S I Sitkin, T S Sall, O N Shalaeva, E V Demyanova, A S Morugina, A F Vinogradova, A V Petrov, A D Nozdrachev
The effects of blood metabolites and model cell culture exometabolites found in the human and animal blood metabolomes have been assessed. Specifically, the influence of carboxylic acids that are structural analogues of amino acids and the drug Aktoflor-C have been studied. Methods of organotypic culturing of rat tissues and Escherichia coli bacterial culturing have been used. It has been found that all the tested compounds either stimulate or inhibit cell proliferation in tissue cultures and proliferation in bacterial cultures...
January 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28419135/an-organotypic-slice-culture-to-study-the-formation-of-calyx-of-held-synapses-in-vitro
#3
Elin Kronander, Nicolas Michalski, Cécile Lebrand, Jean-Pierre Hornung, Ralf Schneggenburger
The calyx of Held, a large axo-somatic relay synapse containing hundreds of presynaptic active zones, is possibly the largest nerve terminal in the mammalian CNS. Studying its initial growth in-vitro might provide insights into the specification of synaptic connection size in the developing brain. However, attempts to maintain calyces of Held in organotypic cultures have not been fruitful in past studies. Here, we describe an organotypic slice culture method in which calyces of Held form in-vitro. We made coronal brainstem slices with an optimized slice angle using newborn mice in which calyces have not yet formed; the presynaptic bushy cells were genetically labeled using the Math5 promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28409994/a-novel-porcine-ex-vivo-retina-culture-model-for-oxidative-stress-induced-by-h%C3%A2-o%C3%A2
#4
José Hurst, Sandra Kuehn, Adelina Jashari, Teresa Tsai, Karl Ulrich Bartz-Schmidt, Sven Schnichels, Stephanie C Joachim
Oxidative stress is a key player in many ophthalmic diseases. However, the role of oxidative stress in most degenerative processes is not yet known. Therefore, accurate and practical models are required to efficiently screen for therapeutics. Porcine eyes are closely related to the human eye, and can be obtained from the abattoir as a by-product of the food industry. Therefore, they offer excellent opportunities for the development of culture models with which to pre-screen potential therapies, while reducing the use of laboratory animals...
March 2017: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28407685/extra-pancreatic-invasion-induces-lipolytic-and-fibrotic-changes-in-the-adipose-microenvironment-with-released-fatty-acids-enhancing-the-invasiveness-of-pancreatic-cancer-cells
#5
Takashi Okumura, Kenoki Ohuchida, Masafumi Sada, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Chika Iwamoto, Daisuke Miura, Yusuke Mizuuchi, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405617/inhibition-of-neuronal-ferroptosis-protects-hemorrhagic-brain
#6
Qian Li, Xiaoning Han, Xi Lan, Yufeng Gao, Jieru Wan, Frederick Durham, Tian Cheng, Jie Yang, Zhongyu Wang, Chao Jiang, Mingyao Ying, Raymond C Koehler, Brent R Stockwell, Jian Wang
Intracerebral hemorrhage (ICH) causes high mortality and morbidity, but our knowledge of post-ICH neuronal death and related mechanisms is limited. In this study, we first demonstrated that ferroptosis, a newly identified form of cell death, occurs in the collagenase-induced ICH model in mice. We found that administration of ferrostatin-1, a specific inhibitor of ferroptosis, prevented neuronal death and reduced iron deposition induced by hemoglobin in organotypic hippocampal slice cultures (OHSCs). Mice treated with ferrostatin-1 after ICH exhibited marked brain protection and improved neurologic function...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28396895/multi-chamber-microfluidic-platform-for-high-precision-skin-permeation-testing
#7
M Alberti, Y Dancik, G Sriram, B Wu, Y L Teo, Z Feng, M Bigliardi-Qi, R G Wu, Z P Wang, P L Bigliardi
The established in vitro tool used for testing the absorption and penetration of chemicals through skin in pharmacology, toxicology and cosmetic science is the static Franz diffusion cell. While widespread, Franz cells are relatively costly, low-throughput and results may suffer from poor reproducibility. Microfluidics has the potential to overcome these drawbacks. In this paper, we present a novel microfluidic skin permeation platform and validate it rigorously against the Franz cell by comparing the transport of 3 model chemicals of varying lipophilicity: caffeine, salicylic acid and testosterone...
April 11, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28387380/a-staged-screening-of-registered-drugs-highlights-remyelinating-drug-candidates-for-clinical-trials
#8
C Eleuteri, S Olla, C Veroni, R Umeton, R Mechelli, S Romano, M C Buscarinu, F Ferrari, G Calò, G Ristori, M Salvetti, C Agresti
There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28384714/organotypic-cultures-of-adult-mouse-retina-morphologic-changes-and-gene-expression
#9
Brigitte Müller, Franziska Wagner, Birgit Lorenz, Knut Stieger
Purpose: The purpose of this study was characterization of adult murine neuroretina in organ culture to investigate its suitability for use in preclinical therapeutic applications. In retinal disorders, neurodegeneration of mature retinal cells takes place. Therefore, neonatal retina cultures are not adequate for therapeutic applications, such as genome editing, as the retina is still developing with cells dividing and differentiating into highly specialized cell types such as photoreceptors...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28375547/demyelination-induced-by-oxidative-stress-is-regulated-by-sphingosine-1-phosphate-receptors
#10
Sinead A O'Sullivan, Maria Velasco-Estevez, Kumlesh K Dev
Oxidative stress is a pathological condition defined as an imbalance between production and removal of reactive oxygen species. This process causes structural cell damage, disrupts DNA repair and induces mitochondrial dysfunction. Many in vitro studies have used direct bolus application of H2 O2 to investigate the role of oxidative stress in cell culture. In this study, using mouse organotypic cerebellar slice cultures, the effects of H2 O2 -induced oxidative stress on myelination state were examined, using bolus concentrations of H2 O2 (0...
April 4, 2017: Glia
https://www.readbyqxmd.com/read/28366471/phosphodiesterase-4-inhibition-restored-hippocampal-long-term-potentiation-after-primary-blast
#11
Edward W Vogel, Fatima N Morales, David F Meaney, Cameron R Bass, Barclay Morrison
Due to recent military conflicts and terrorist attacks, blast-induced traumatic brain injury (bTBI) presents a health concern for military and civilian personnel alike. Although secondary blast (penetrating injury) and tertiary blast (inertia-driven brain deformation) are known to be injurious, the effects of primary blast caused by the supersonic shock wave interacting with the skull and brain remain debated. Our group previously reported that in vitro primary blast exposure reduced long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) and that primary blast affects key proteins governing LTP...
March 31, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28333312/establishment-maintenance-and-functional-integrity-of-the-blood-testis-barrier-in-organotypic-cultures-of-fresh-and-frozen-thawed-prepubertal-mouse-testes
#12
C Rondanino, A Maouche, L Dumont, A Oblette, N Rives
STUDY QUESTION: Can the spatio-temporal formation of an intact blood-testis barrier (BTB), which is essential for the progression of spermatogenesis, be reproduced in cultures of fresh or frozen/thawed prepubertal mouse testes? SUMMARY ANSWER: Organotypic cultures allow the establishment and maintenance of major BTB components and the formation of a functional BTB in mouse testicular tissues. WHAT IS KNOWN ALREADY: In vitro maturation of prepubertal testicular tissues is a promising approach to restore fertility in adult survivors of childhood cancer...
March 17, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28330786/investigating-acetaminophen-hepatotoxicity-in-multi-cellular-organotypic-liver-models
#13
Sophia M Orbach, Margaret E Cassin, Marion F Ehrich, Padmavathy Rajagopalan
In vivo studies clearly demonstrate the participation and subsequent death of non-parenchymal liver cells (NPCs) with corresponding hepatocyte effects. This results in a critical need to investigate how major liver cell types function cohesively during hepatotoxicity. However, virtually no studies replicate these phenomena in vitro. We report the design of multi-cellular three-dimensional (3D) organotypic liver models of primary rat hepatocytes, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs)...
March 19, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28322333/squamous-epitheliotropism-of-enterovirus-a71-in-human-epidermis-and-oral-mucosa
#14
Win Kyaw Phyu, Kien Chai Ong, Chee Kwan Kong, Abdul Khalil Alizan, Tindivanam Muthurangam Ramanujam, Kum Thong Wong
Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315313/transforming-growth-factors-%C3%AE-and-%C3%AE-are-essential-for-modeling-cholangiocarcinoma-desmoplasia-and-progression-in-a-three-dimensional-organotypic-culture-model
#15
Miguel A Manzanares, Akihiro Usui, Deanna J Campbell, Catherine I Dumur, Gabrielle T Maldonado, Michel Fausther, Jonathan A Dranoff, Alphonse E Sirica
To gain insight into the cellular and molecular interactions mediating the desmoplastic reaction and aggressive malignancy of mass-forming intrahepatic cholangiocarcinoma (ICC), we modeled ICC desmoplasia and progression in vitro. A unique three-dimensional (3D) organotypic culture model was established; within a dilute collagen-type I hydrogel, a novel clonal strain of rat cancer-associated myofibroblasts (TDFSM) was co-cultured with a pure rat cholangiocarcinoma cell strain (TDECC) derived from the same ICC type as TDFSM...
March 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28306742/hpv16-and-18-genome-amplification-show-different-e4-dependence-with-16e4-enhancing-e1-nuclear-accumulation-and-replicative-efficiency-via-its-cell-cycle-arrest-and-kinase-activation-functions
#16
Nagayasu Egawa, Qian Wang, Heather M Griffin, Isao Murakami, Deborah Jackson, Radma Mahmood, John Doorbar
To clarify E1^E4's role during high-risk HPV infection, the E4 proteins of HPV16 and 18 were compared side by side using an isogenic keratinocyte differentiation model. While no effect on cell proliferation or viral genome copy number was observed during the early phase of either virus life cycle, time-course experiments showed that viral genome amplification and L1 expression were differently affected upon differentiation, with HPV16 showing a much clearer E4 dependency. Although E4 loss never completely abolished genome amplification, its more obvious contribution in HPV16 focused our efforts on 16E4...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28300838/membrane-association-and-release-of-wild-type-and-pathological-tau-from-organotypic-brain-slice-cultures
#17
Cara L Croft, Matthew A Wade, Ksenia Kurbatskaya, Pavlina Mastrandreas, Martina M Hughes, Emma C Phillips, Amy M Pooler, Michael S Perkinton, Diane P Hanger, Wendy Noble
The spatiotemporal transmission of pathological tau in the brain is characteristic of Alzheimer's disease. Release of both soluble and abnormal tau species from healthy neurons is increased upon stimulation of neuronal activity. It is not yet understood whether the mechanisms controlling soluble tau release from healthy neurons is the same as those involved in the spread of pathological tau species. To begin to understand these events, we have studied tau distribution and release using organotypic brain slice cultures...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28300597/gli2-is-a-regulator-of-%C3%AE-catenin-and-is-associated-with-loss-of-e-cadherin-cell-invasiveness-and-long-term-epidermal-regeneration
#18
Eleni Pantazi, Emilios Gemenetzidis, Muy-Teck Teh, Sreekanth Vootukuri Reddy, Gary Warnes, Chris Evagora, Giuseppe Trigiante, Michael P Philpott
Uncontrolled HH/GLI and WNT/β-catenin signaling are important events in the genesis of many cancers including skin cancer and are often implicated in tumour progression, invasion and metastasis. However, due to the complexity and context-dependency of both pathways, little is known about HH and WNT interactions in human carcinogenesis. In the current study we provide evidence of HH/GLI2-WNT/β-catenin signaling crosstalk in human keratinocytes. Over-expression of GLI2ΔN in human keratinocytes resulted in cytoplasmic accumulation and nuclear relocalization of β-catenin in vitro and in 3D-organotypic cultures, accompanied by upregulation of WNT genes...
March 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28292843/translational-applications-of-adult-stem-cell-derived-organoids
#19
REVIEW
Jarno Drost, Hans Clevers
Adult stem cells from a variety of organs can be expanded long-term in vitro as three-dimensional organotypic structures termed organoids. These adult stem cell-derived organoids retain their organ identity and remain genetically stable over long periods of time. The ability to grow organoids from patient-derived healthy and diseased tissue allows for the study of organ development, tissue homeostasis and disease. In this Review, we discuss the generation of adult stem cell-derived organoid cultures and their applications in in vitro disease modeling, personalized cancer therapy and regenerative medicine...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28285100/engineering-epithelial-stromal-interactions-in-vitro-for-toxicology-assessment
#20
REVIEW
David G Belair, Barbara D Abbott
Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance...
March 8, 2017: Toxicology
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