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https://www.readbyqxmd.com/read/28088609/leukemia-inhibitory-factor-impairs-structural-and-neurochemical-development-of-rat-visual-cortex-in-vivo
#1
Maren Engelhardt, Graziella di Cristo, Jochen Grabert, Silke Patz, Lamberto Maffei, Nicoletta Berardi, Petra Wahle
Minipump infusions into visual cortex in vivo at the onset of the critical period have revealed that the proinflammatory cytokine leukemia inhibitory factor (LIF) delays the maturation of thalamocortical projection neurons of the lateral geniculate nucleus, and tecto-thalamic projection neurons of the superior colliculus, and cortical layer IV spiny stellates and layer VI pyramidal neurons. Here, we report that P12-20 LIF infusion inhibits somatic maturation of pyramidal neurons and of all interneuron types in vivo...
January 11, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28086931/the-release-and-trans-synaptic-transmission-of-tau-via-exosomes
#2
Yipeng Wang, Varun Balaji, Senthilvelrajan Kaniyappan, Lars Krüger, Stephan Irsen, Katharina Tepper, RamReddy Chandupatla, Walter Maetzler, Anja Schneider, Eckhard Mandelkow, Eva-Maria Mandelkow
BACKGROUND: Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages ("Braak stages"). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood...
January 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28082416/a-brain-penetrant-raf-dimer-antagonist-for-the-noncanonical-braf-oncoprotein-of-pediatric-low-grade-astrocytomas
#3
Yu Sun, John A Alberta, Catherine Pilarz, David Calligaris, Emily J Chadwick, Shakti H Ramkissoon, Lori A Ramkissoon, Veronica Matia Garcia, Emanuele Mazzola, Liliana Goumnerova, Michael Kane, Zhan Yao, Mark W Kieran, Keith L Ligon, William C Hahn, Levi A Garraway, Neal Rosen, Nathanael S Gray, Nathalie Y Agar, Sara J Buhrlage, Rosalind A Segal, Charles D Stiles
BACKGROUND: Activating mutations or structural rearrangements in BRAF are identified in roughly 75% of all pediatric low-grade astrocytomas (PLGAs). However, first-generation RAF inhibitors approved for adult melanoma have poor blood-brain penetrance and are only effective on tumors that express the canonical BRAFV600E oncoprotein, which functions as a monomer. These drugs (type I antagonists that target the "DFG-in" conformation of the kinase) fail to block signaling via KIAA1549:BRAF, a truncation/fusion BRAF oncoprotein which functions as a dimer and is found in the most common form of PLGA...
January 12, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28069458/loganin-enhances-long-term-potentiation-and-recovers-scopolamine-induced-learning-and-memory-impairments
#4
Eun-Sang Hwang, Hyun-Bum Kim, Seok Lee, Min-Ji Kim, Sung-Ok Lee, Seung-Moo Han, Sungho Maeng, Ji-Ho Park
Although the incidence rate of dementia is rapidly growing in the aged population, therapeutic and preventive reagents are still suboptimal. Various model systems are used for the development of such reagents in which scopolamine is one of the favorable pharmacological tools widely applied. Loganin is a major iridoid glycoside obtained from Corni fructus (Cornusofficinaliset Zucc) and demonstrated to have anti-inflammatory, anti-tumor and osteoporosis prevention effects. It has also been found to attenuate Aβ-induced inflammatory reactions and ameliorate memory deficits induced by scopolamine...
January 6, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28064442/tumor-derived-spheroids-relevance-to-cancer-stem-cells-and-clinical-applications
#5
REVIEW
Tatsuya Ishiguro, Hirokazu Ohata, Ai Sato, Kaoru Yamawaki, Takayuki Enomoto, Koji Okamoto
Recently, many types of in vitro three-dimensional (3D) culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3D culture methods aim to preserve the biological characteristics of original tumors better than conventional two-dimensional (2D) monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28061478/mitotic-control-of-human-papillomavirus-genome-containing-cells-is-regulated-by-the-function-of-the-pdz-binding-motif-of-the-e6-oncoprotein
#6
Elizabeth K Marsh, Craig P Delury, Nicholas J Davies, Christopher J Weston, Mohammed A L Miah, Lawrence Banks, Joanna L Parish, Martin R Higgs, Sally Roberts
The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28052368/synthesis-and-activity-of-the-salicylic-acid-ester-of-bakuchiol-in-psoriasis-surrogate-keratinocytes-and-skin-substitutes
#7
S Ma, K Gobis, W R Swindell, R Chaudhuri, R Bojanowski, K Bojanowski
BACKGROUND: Topical retinoids are effective in retarding skin ageing and restoring homeostasis in skin conditions such as psoriasis. However their adverse effects (AEs), which include irritation (retinoid dermatitis), photosensitivity and teratogenicity, limit their use and patient compliance. Development of retinoid analogues with minimal AEs would allow a broader and more compliant use. AIM: To synthesise a novel molecule, bakuchiol salicylate (bakusylan), with a modulatory gene expression profile similar to retinoids, using as reference three prescription retinoids: tretinoin, tazarotene and adapalene...
January 4, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28050314/biocompatibility-study-of-lithium-disilicate-and-zirconium-oxide-ceramics-for-esthetic-dental-abutments
#8
Céline Brunot-Gohin, Jean-Luc Duval, Sandra Verbeke, Kayla Belanger, Isabelle Pezron, Gérard Kugel, Dominique Laurent-Maquin, Sophie Gangloff, Christophe Egles
PURPOSE: The increasing demand for esthetically pleasing results has contributed to the use of ceramics for dental implant abutments. The aim of this study was to compare the biological response of epithelial tissue cultivated on lithium disilicate (LS2) and zirconium oxide (ZrO2) ceramics. Understanding the relevant physicochemical and mechanical properties of these ceramics will help identify the optimal material for facilitating gingival wound closure. METHODS: Both biomaterials were prepared with 2 different surface treatments: raw and polished...
December 2016: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/28048945/organotypic-spheroid-culture-to-mimic-radiation-induced-salivary-hypofunction
#9
H S Shin, H Y An, J S Choi, H J Kim, J Y Lim
Radiation treatment often leads to irreversible damage to normal salivary glands (SGs) because of their proximity to head and neck cancers. Optimization of the in vitro model of irradiation (IR)-induced SG damage is warranted to investigate pathophysiology and monitor treatment outcome. Here, we present an organotypic spheroid culture model to investigate the impact of IR on SGs and the mechanisms underlying IR-induced structural and functional changes. Human parotid epithelial cells were obtained from human parotid glands and plated on either plastic plates or Matrigel...
December 1, 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/28036084/preferential-enhancement-of-sensory-and-motor-axon-regeneration-by-combining-extracellular-matrix-components-with-neurotrophic-factors
#10
Daniel Santos, Francisco González-Pérez, Guido Giudetti, Silvestro Micera, Esther Udina, Jaume Del Valle, Xavier Navarro
After peripheral nerve injury, motor and sensory axons are able to regenerate but inaccuracy of target reinnervation leads to poor functional recovery. Extracellular matrix (ECM) components and neurotrophic factors (NTFs) exert their effect on different neuronal populations creating a suitable environment to promote axonal growth. Here, we assessed in vitro and in vivo the selective effects of combining different ECM components with NTFs on motor and sensory axons regeneration and target reinnervation. Organotypic cultures with collagen, laminin and nerve growth factor (NGF)/neurotrophin-3 (NT3) or collagen, fibronectin and brain-derived neurotrophic factor (BDNF) selectively enhanced sensory neurite outgrowth of DRG neurons and motor neurite outgrowth from spinal cord slices respectively...
December 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28035373/cancer-associated-peritoneal-mesothelial-cells-lead-the-formation-of-pancreatic-cancer-peritoneal-dissemination
#11
Toshiya Abe, Kenoki Ohuchida, Kazuhiro Koikawa, Sho Endo, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Makoto Hashizume, Masafumi Nakamura
The interaction between the cancer cells and the peritoneal mesothelial cells (PMCs) plays an important role in the peritoneal dissemination in several types of cancer. However, the role of PMCs in the peritoneal dissemination of pancreatic cancer remains unclear. In the present study, we investigated the interaction between thr pancreatic cancer cells (PCCs) and the PMCs in the formation of peritoneal dissemination in vitro and in vivo. The tumor-stromal interaction of PCCs and PMCs significantly enhanced their mobility and invasiveness and enhanced the proliferation and anoikis resistance of PCCs...
December 30, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/28030813/stattic-and-metformin-inhibit-brain-tumor-initiating-cells-by-reducing-stat3-phosphorylation
#12
Verena Leidgens, Judith Proske, Lisa Rauer, Sylvia Moeckel, Kathrin Renner, Ulrich Bogdahn, Markus J Riemenschneider, Martin Proescholdt, Arabel Vollmann-Zwerenz, Peter Hau, Corinna Seliger
Glioblastoma (GBM) is the most common and malignant type of primary brain tumor and associated with a devastating prognosis. Signal transducer and activator of transcription number 3 (STAT3) is an important pathogenic factor in GBM and can be specifically inhibited with Stattic. Metformin inhibits GBM cell proliferation and migration. Evidence from other tumor models suggests that metformin inhibits STAT3, but there is no specific data on brain tumor initiating cells (BTICs).We explored proliferation and migration of 7 BTICs and their differentiated counterparts (TCs) after treatment with Stattic, metformin or the combination thereof...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028198/sex-dependent-regulation-of-aromatase-mediated-synaptic-plasticity-in-the-basolateral-amygdala
#13
Roland A Bender, Lepu Zhou, Ricardo Vierk, Nicola Brandt, Alexander Keller, Christine E Gee, Michael K E Schäfer, Gabriele M Rune
: The basolateral amygdala (BLA) integrates sensory input from cortical and subcortical regions, a function that requires marked synaptic plasticity. Here we provide evidence that cytochrome P450 aromatase (AROM), the enzyme converting testosterone to 17β-estradiol (E2), contributes to the regulation of this plasticity in a sex-specific manner. We show that AROM is expressed in the BLA, particularly in the basolateral nucleus (BL), in male and female rodents. Systemic administration of the AROM-inhibitor letrozole reduced spine synapse density in the BL of adult female mice, but not in the BL of male mice...
December 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28025120/comparative-systems-toxicology-analysis-of-cigarette-smoke-and-aerosol-from-a-candidate-modified-risk-tobacco-product-in-organotypic-human-gingival-epithelial-cultures-a-3-day-repeated-exposure-study
#14
Filippo Zanetti, Bjoern Titz, Alain Sewer, Giuseppe Lo Sasso, Elena Scotti, Walter K Schlage, Carole Mathis, Patrice Leroy, Shoaib Majeed, Laura Ortega Torres, Brian R Keppler, Elamin Ashraf, Keyur Trivedi, Emmanuel Guedj, Florian Martin, Stefan Frentzel, Nikolai V Ivanov, Manuel C Peitsch, Julia Hoeng
Smoking is one of the major lifestyle-related risk factors for periodontal diseases. Modified risk tobacco products (MRTP) offer a promising alternative in the harm reduction strategy for adult smokers unable to quit. Using a systems toxicology approach, we investigated and compared the exposure effects of a reference cigarette (3R4F) and a heat-not-burn technology-based candidate MRTP, the Tobacco Heating System (THS) 2.2. Human gingival epithelial organotypic cultures were repeatedly exposed (3 days) for 28 min at two matching concentrations of cigarette smoke (CS) or THS2...
December 23, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28012853/rat-brain-sagittal-organotypic-slice-cultures-as-an-ex-vivo-dopamine-cell-loss-system
#15
Amy McCaughey-Chapman, Bronwen Connor
BACKGROUND: Organotypic brain slice cultures are a useful tool to study neurological function as they provide a more complex, 3-dimensional system than standard 2-dimensional in vitro cell cultures. NEW METHOD: Building on a previously developed mouse brain slice culture protocol, we have developed a rat sagittal brain slice culture system as an ex vivo model of dopamine cell loss. RESULTS: We show that rat brain organotypic slice cultures remain viable for up to 6 weeks in culture...
December 21, 2016: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28008153/pten-mediates-the-cross-talk-between-breast-and-glial-cells-in-brain-metastases-leading-to-rapid-disease-progression
#16
Ina Hohensee, Han-Ning Chuang, Astrid Grottke, Stefan Werner, Alexander Schulte, Stefan Horn, Katrin Lamszus, Kai Bartkowiak, Isabell Witzel, Manfred Westphal, Jakob Matschke, Markus Glatzel, Manfred Jücker, Tobias Pukrop, Klaus Pantel, Harriet Wikman
Despite improvement of therapeutic treatments for breast cancer, the development of brain metastases has become a major limitation to life expectancy for many patients. Brain metastases show very commonly alterations in EGFR and HER2 driven pathways, of which PTEN is an important regulator. Here, we analyzed PTEN expression in 111 tissue samples of breast cancer brain metastases (BCBM). Loss of PTEN was found in a substantial proportion of BCBM samples (48.6%) and was significantly associated with triple-negative breast cancer (67...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28007893/young-microglia-restore-amyloid-plaque-clearance-of-aged-microglia
#17
Anna Daria, Alessio Colombo, Gemma Llovera, Heike Hampel, Michael Willem, Arthur Liesz, Christian Haass, Sabina Tahirovic
Alzheimer's disease (AD) is characterized by deposition of amyloid plaques, neurofibrillary tangles, and neuroinflammation. In order to study microglial contribution to amyloid plaque phagocytosis, we developed a novel ex vivo model by co-culturing organotypic brain slices from up to 20-month-old, amyloid-bearing AD mouse model (APPPS1) and young, neonatal wild-type (WT) mice. Surprisingly, co-culturing resulted in proliferation, recruitment, and clustering of old microglial cells around amyloid plaques and clearance of the plaque halo...
December 21, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28007556/roles-of-ph-and-the-na-h-exchanger-nhe1-in-cancer-from-cell-biology-and-animal-models-to-an-emerging-translational-perspective
#18
REVIEW
Christian Stock, Stine Falsig Pedersen
Acidosis is characteristic of the solid tumor microenvironment. Tumor cells, because they are highly proliferative and anabolic, have greatly elevated metabolic acid production. To sustain a normal cytosolic pH homeostasis they therefore need to either extrude excess protons or to neutralize them by importing HCO3(-), in both cases causing extracellular acidification in the poorly perfused tissue microenvironment. The Na(+)/H(+) exchanger isoform 1 (NHE1) is a ubiquitously expressed acid-extruding membrane transport protein, and upregulation of its expression and/or activity is commonly correlated with tumor malignancy...
December 19, 2016: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/27997067/rotenone-and-elevated-extracellular-potassium-concentration-induce-cell-specific-fibrillation-of-%C3%AE-synuclein-in-axons-of-cholinergic-enteric-neurons-in-the-guinea-pig-ileum
#19
D F Sharrad, B N Chen, W P Gai, N Vaikath, O M El-Agnaf, S J H Brookes
BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder that results in the widespread loss of select classes of neurons throughout the nervous system. The pathological hallmarks of Parkinson's disease are Lewy bodies and neurites, of which α-synuclein fibrils are the major component. α-Synuclein aggregation has been reported in the gut of Parkinson's disease patients, even up to a decade before motor symptoms, and similar observations have been made in animal models of disease...
November 7, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27989506/novel-androgen-induced-activity-of-an-antimicrobial-%C3%AE-defensin-regulation-of-wolffian-duct-morphogenesis
#20
Camilla M Ribeiro, Lucas G A Ferreira, Daniel S Thimoteo, Lee B Smith, Barry T Hinton, Maria Christina W Avellar
The Wolffian duct (WD) undergoes morphological changes induced by androgens to form the epididymis, which is an organ essential for sperm maturation. Androgen action in WD epithelium involves paracrine factors of mesenchymal origin that function by still poorly understood mechanisms. Here we studied the antimicrobial β-defensin SPAG11C as a new player in duct morphogenesis, localized prenatally in the WD mesenchyme. Organotypic culture of rat WDs and tissues from Androgen Receptor (AR) knockout mice (ARKO) were used...
December 15, 2016: Molecular and Cellular Endocrinology
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