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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/28416797/unification-of-de-novo-and-acquired-ibrutinib-resistance-in-mantle-cell-lymphoma
#4
Xiaohong Zhao, Tint Lwin, Ariosto Silva, Bijal Shah, Jiangchuan Tao, Bin Fang, Liang Zhang, Kai Fu, Chengfeng Bi, Jiannong Li, Huijuan Jiang, Mark B Meads, Timothy Jacobson, Maria Silva, Allison Distler, Lancia Darville, Ling Zhang, Ying Han, Dmitri Rebatchouk, Maurizio Di Liberto, Lynn C Moscinski, John M Koomen, William S Dalton, Kenneth H Shain, Michael Wang, Eduardo Sotomayor, Jianguo Tao
The novel Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated high response rates in B-cell lymphomas; however, a growing number of ibrutinib-treated patients relapse with resistance and fulminant progression. Using chemical proteomics and an organotypic cell-based drug screening assay, we determine the functional role of the tumour microenvironment (TME) in ibrutinib activity and acquired ibrutinib resistance. We demonstrate that MCL cells develop ibrutinib resistance through evolutionary processes driven by dynamic feedback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin-β1 signalling...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28416302/effect-of-bacterial-biofilm-on-the-osteogenic-differentiation-of-stem-cells-of-apical-papilla
#5
Lakshmi Vishwanat, Rose Duong, Koyo Takimoto, Linda Phillips, Claudia O Espitia, Anibal Diogenes, Shivani B Ruparel, David Kolodrubetz, Nikita B Ruparel
INTRODUCTION: Although clinical success in regenerative endodontics is substantially high, histological success is limited to finding bone/cementum-like tissue instead of dentin within the canal space. The aims of this study were to investigate (1) the effect of bacterial biofilm on osteogenic gene expression in stem cells of the apical papilla (SCAP) and (2) the effect of bacterial antigens on the functional differentiation of SCAP into a mineralizing phenotype. METHODS: Using an ex vivo organotypic root canal model and an American Association of Endontists-recommended regenerative endodontic procedures, we evaluated SCAP differentiation in the presence and absence of an Enterococcus faecalis biofilm...
April 14, 2017: Journal of Endodontics
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
#6
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
#7
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
#8
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/28401934/vaginal-lactic-acid-elicits-an-anti-inflammatory-response-from-human-cervicovaginal-epithelial-cells-and-inhibits-production-of-pro-inflammatory-mediators-associated-with-hiv-acquisition
#9
A C Hearps, D Tyssen, D Srbinovski, L Bayigga, D J D Diaz, M Aldunate, R A Cone, R Gugasyan, D J Anderson, G Tachedjian
Inflammation in the female reproductive tract (FRT) is associated with increased HIV transmission. Lactobacillus spp. dominate the vaginal microbiota of many women and their presence is associated with reduced HIV acquisition. Here we demonstrate that lactic acid (LA), a major organic acid metabolite produced by lactobacilli, mediates anti-inflammatory effects on human cervicovaginal epithelial cells. Treatment of human vaginal and cervical epithelial cell lines with LA (pH 3.9) elicited significant increases in the production of the anti-inflammatory cytokine IL-1RA...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28396895/multi-chamber-microfluidic-platform-for-high-precision-skin-permeation-testing
#10
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
#11
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
#12
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
#13
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/28371541/an-engineered-cell-instructive-stroma-for-the-fabrication-of-a-novel-full-thickness-human-cervix-equivalent-in-vitro
#14
Vincenza De Gregorio, Giorgia Imparato, Francesco Urciuolo, Maria L Tornesello, Clorinda Annunziata, Franco M Buonaguro, Paolo A Netti
There is a growing interest for developing organotypic cervical models by using primary cervical cells that are able to reproduce the physiological relevant stromal microenvironment and the distinctive histology of the native cervical epithelium. Here for the first time it is reported the production of an organotypic cervical model featured by a scaffold-free stromal tissue resembling the extracellular matrix (ECM) composition and organization of the native counterpart as well as a completely well-differentiated epithelium...
March 29, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28366471/phosphodiesterase-4-inhibition-restored-hippocampal-long-term-potentiation-after-primary-blast
#15
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/28360856/east-indian-sandalwood-oil-eiso-alleviates-inflammatory-and-proliferative-pathologies-of-psoriasis
#16
Manju Sharma, Corey Levenson, Ian Clements, Paul Castella, Kurt Gebauer, Michael E Cox
Psoriasis, a chronic inflammatory skin disease marked by hyper proliferation and aberrant differentiation of keratinocytes, affects 2-3% of the world's population. Research into the pathogenesis of psoriasis has been hampered by the lack of models that accurately reflect the biology of the psoriatic phenotype. We have previously reported that East Indian Sandalwood oil (EISO) has significant anti-inflammatory properties in skin models and hypothesized that EISO might provide therapeutic benefit to psoriasis patients due to its anti-inflammatory and anti-proliferative properties...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28340598/myelin-specific-multiple-sclerosis-antibodies-cause-complement-dependent-oligodendrocyte-loss-and-demyelination
#17
Yiting Liu, Katherine S Given, Danielle E Harlow, Adeline M Matschulat, Wendy B Macklin, Jeffrey L Bennett, Gregory P Owens
Intrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets and pathogenic effects of MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant antibodies (rAbs) from clonally-expanded plasmablasts recovered from MS patient CSF. Among these were a subset of myelin-specific MS rAbs. We examined their immunoreactivity to mouse organotypic cerebellar slices by live binding and evaluated tissue injury in the presence and absence of human complement...
March 24, 2017: Acta Neuropathologica Communications
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
#18
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
#19
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/28330493/loss-of-mmp-8-in-ductal-carcinoma-in-situ-dcis-associated-myoepithelial-cells-contributes-to-tumour-promotion-through-altered-adhesive-and-proteolytic-function
#20
Muge Sarper, Michael D Allen, Jenny Gomm, Linda Haywood, Julie Decock, Sally Thirkettle, Ahsen Ustaoglu, Shah-Jalal Sarker, John Marshall, Dylan R Edwards, J Louise Jones
BACKGROUND: Normal myoepithelial cells (MECs) play an important tumour-suppressor role in the breast but display an altered phenotype in ductal carcinoma in situ (DCIS), gaining tumour-promoter functions. Matrix metalloproteinase-8 (MMP-8) is expressed by normal MECs but is lost in DCIS. This study investigated the function of MMP-8 in MECs and the impact of its loss in DCIS. METHODS: Primary normal and DCIS-associated MECs, and normal (N-1089) and DCIS-modified myoepithelial (β6-1089) cell lines, were used to assess MMP-8 expression and function...
March 23, 2017: Breast Cancer Research: BCR
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