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https://www.readbyqxmd.com/read/29311744/mutations-in-vps15-perturb-neuronal-migration-in-mice-and-are-associated-with-neurodevelopmental-disease-in-humans
#1
Thomas Gstrein, Andrew Edwards, Anna Přistoupilová, Ines Leca, Martin Breuss, Sandra Pilat-Carotta, Andi H Hansen, Ratna Tripathy, Anna K Traunbauer, Tobias Hochstoeger, Gavril Rosoklija, Marco Repic, Lukas Landler, Viktor Stránecký, Gerhard Dürnberger, Thomas M Keane, Johannes Zuber, David J Adams, Jonathan Flint, Tomas Honzik, Marta Gut, Sergi Beltran, Karl Mechtler, Elliott Sherr, Stanislav Kmoch, Ivo Gut, David A Keays
The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling...
January 8, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29296915/erythrocyte-%C3%AE-spectrin-can-be-genetically-targeted-to-protect-mice-from-malaria
#2
Patrick M Lelliott, Hong Ming Huang, Matthew W Dixon, Arman Namvar, Adam J Blanch, Vijay Rajagopal, Leann Tilley, Cevayir Coban, Brendan J McMorran, Simon J Foote, Gaetan Burgio
The malaria parasite hijacks host erythrocytes to shield itself from the immune system and proliferate. Red blood cell abnormalities can provide protection from malaria by impeding parasite invasion and growth within the cell or by compromising the ability of parasites to avoid host clearance. Here, we describe 2 N-ethyl-N-nitrosourea-induced mouse lines, SptbMRI26194 and SptbMRI53426 , containing single-point mutations in the erythrocyte membrane skeleton gene, β spectrin (Sptb), which exhibit microcytosis but retain a relatively normal ratio of erythrocyte surface area to volume and are highly resistant to rodent malaria...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288005/ex-vivo-culture-of-tumor-cells-from-n-methyl-n-nitrosourea-induced-bladder-cancer-in-rats-development-of-organoids-and-an-immortalized-cell-line
#3
Takahiro Yoshida, Max Kates, Nikolai A Sopko, Xiaopu Liu, Alok K Singh, William R Bishai, Gregory Joice, David J McConkey, Trinity J Bivalacqua
OBJECTIVE: We ex vivo cultured primary tumor cells from N-methyl-N-nitrosourea (MNU)-induced bladder tumors in rats and established an immortalized cell line from them. MATERIALS AND METHODS: Bladder tumors in rats were induced by instillation of MNU into the murine bladder. Primary tumor cells were prepared by the cancer-tissue originated spheroid method. An immortalized cell line was established by co-culture with fibroblasts. The cultured tumor cells were molecularly and functionally characterized by quantitative real-time polymerase chain reaction, Western blot, growth assay, and transwell migration assay...
December 26, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29285012/evaluation-of-in-vitro-and-in-vivo-anticancer-potential-of-two-5-acetamido-chalcones-against-breast-cancer
#4
Sonal Wankhede, Nitesh Kumar, Lalitha Simon, Subhankar Biswas, Karthik Gourishetti, Grandhi Venkata Ramalingayya, Mit Joshi, C Mallikarjuna Rao
Two 5'acetamido chalcones, C1 and C2 were synthesized by Claisen-Schmidt condensation method and characterized by IR, LC-MS, 1H NMR and 13C NMR. These compounds were evaluated for anticancer activity in vitro in breast cancer cell lines (MCF-7 and MDA-MB-231) using MTT assay, anti-metastatic assay, apoptotic screening by AO/EB staining and in vivo in N-Methyl-N-nitrosourea (MNU) induced breast carcinoma model. Sprague-Dawley rats with developed tumors (50 mg/kg MNU i.p.) were grouped in four, namely MNU control (0...
2017: EXCLI Journal
https://www.readbyqxmd.com/read/29209984/intravesical-thalidomide-boosts-bacillus-calmette-gu%C3%A3-rin-bcg-in-non-muscle-invasive-bladder-cancer-treatment
#5
Gabriela R Passos, Juliana A Camargo, Karen L Ferrari, Mário J A Saad, Amilcar C de Mattos, Leonardo O Reis
The aim of this study was to explore the efficacy of intravesical Thalidomide (immunomodulatory, anti-inflammatory and anti-angiogenic) added to BCG using an immune competent autochthonous orthotopic NMIBC animal model. Female Fischer 344 rats, 7 weeks of age, received every 2 weeks for four times, a dose of 1.5 mg/kg of N-methyl-N-nitrosourea (MNU) intravesically. The rats were randomized into four groups (n = 10 per group) to receive intravesical treatment once a week for 6 weeks as follows: control (0...
December 4, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29174504/intravesical-immunomodulatory-imiquimod-enhances-bacillus-calmette-gu%C3%A3-rin-downregulation-of-nonmuscle-invasive-bladder-cancer
#6
Juliana A Camargo, Gabriela R Passos, Karen L Ferrari, Athanase Billis, Mário J A Saad, Leonardo O Reis
BACKGROUND: The Toll-like receptor (TLR)2/4 agonist bacillus Calmette-Guérin (BCG), although not failure proof, has been the most efficient immunomodulatory treatment of immunogenic nonmuscle-invasive bladder cancer (NMIBC) for > 40 years. We investigated the role of the immunomodulatory molecule TLR7 agonist imiquimod through the BCG key receptors TLR2/4 and the main downstream molecules of the mammalian target of rapamycin pathway in NMIBC treatment. MATERIALS AND METHODS: A total of 40 Fischer-344 rats, 7 weeks old, received 4 doses of 1...
November 7, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29154133/signaling-molecule-methylglyoxal-ameliorates-cadmium-injury-in-wheat-triticum-aestivum-l-by-a-coordinated-induction-of-glutathione-pool-and-glyoxalase-system
#7
Zhong-Guang Li, Qian Nie, Cong-Li Yang, Yue Wang, Zhi-Hao Zhou
Methylglyoxal (MG) now is found to be an emerging signaling molecule. It can relieve the toxicity of cadmium (Cd), however its alleviating mechanism still remains unknown. In this study, compared with the Cd-stressed seedlings without MG treatment, MG treatment could stimulate the activities of glutathione reductase (GR) and gamma-glutamylcysteine synthetase (γ-ECS) in Cd-stressed wheat seedlings, which in turn induced an increase of reduced glutathione (GSH). Adversely, the activated enzymes related to GSH biosynthesis and increased GSH were weakened by N-acetyl-L-cysteine (NAC, MG scavenger), 2,4-dihydroxy-benzylamine (DHBA) and 1,3-bischloroethyl-nitrosourea (BCNU, both are specific inhibitors of GR), buthionine sulfoximine (BSO, a specific inhibitors of GSH biosynthesis), and N-ethylmaleimide (NEM, GSH scavenger), respectively...
November 16, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29151256/melatonin-and-metformin-diminish-oxidative-stress-in-heart-tissue-in-a-rat-model-of-high-fat-diet-and-mammary-carcinogenesis
#8
Natalia Kurhaluk, Bianka Bojkova, Marek Radkowski, Olga V Zaitseva, Svitlana Kyriienko, Urszula Demkow, Pawel J Winklewski
The aim of this study was to determine the effects of long-term administration of the oral antidiabetic metformin or the pineal hormone melatonin, and a combination thereof, in preventing oxidative stress in the heart tissue of female Sprague-Dawley rats with mammary tumors induced by N-methyl-N-nitrosourea (NMU) (50 mg/kg) given on the 42nd postnatal day. Metformin and melatonin were administered 12 days before and 16 weeks after the carcinogen. During the experiment, all animals were fed a high fat diet (10% total fat, 2...
November 19, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29126840/neuroprotective-effect-of-cannabinoid-receptor-1-antagonist-in-the-mnu-induced-retinal-degeneration-model
#9
Yuanyuan Chen, Xue Luo, Shiliang Liu, Yin Shen
Endocannabinoid system involves in neuroprotective effects on the central neural system. The cannabinoid receptor 1 (CB1R) is widely expressed in the mouse retina. However, the role of cannabinoid receptors in the retina remains unclear. In this work, we established a photoreceptor degeneration mouse model via N-methyl-N-nitrosourea (MNU) administration to identify the neuroprotective effects of cannabinoid receptors. The MNU-induced retinal degeneration behaves similarly to that in the human retinitis pigmentosa (RP)...
November 7, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/29114374/prevention-of-chemotherapy-induced-nephrotoxicity-in-children-with-cancer
#10
REVIEW
Fatemeh Ghane Sharbaf, Hamid Farhangi, Farahnak Assadi
Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX). Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI), tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS), and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/29107289/disruption-of-the-homeodomain-transcription-factor-orthopedia-homeobox-otp-is-associated-with-obesity-and-anxiety
#11
Lee Moir, Elena G Bochukova, Rebecca Dumbell, Gareth Banks, Rasneer S Bains, Patrick M Nolan, Cheryl Scudamore, Michelle Simon, Kimberly A Watson, Julia Keogh, Elana Henning, Audrey Hendricks, Stephen O'Rahilly, Inês Barroso, Adrienne E Sullivan, David C Bersten, Murray L Whitelaw, Susan Kirsch, Elizabeth Bentley, I Sadaf Farooqi, Roger D Cox
OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29105885/emp-induced-bbb-disruption-enhances-drug-delivery-to-glioma-and-increases-treatment-efficacy-in-rats
#12
Kangchu Li, Keying Zhang, Shenglong Xu, Xiaowu Wang, Yongchun Zhou, Yan Zhou, Peng Gao, Jiajin Lin, Guirong Ding, Guozhen Guo
Chemotherapy on gliomas is not satisfactorily efficient because the presence of blood-brain barriers (BBB) leads to inadequate exposure of tumor cells to administered drugs. In order to facilitate chemotherapeutics to penetrate BBB and increase the treatment efficacy of gliomas, electromagnetic pulse (EMP) was applied and the 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU) lomustine concentration in tumor tissue, tumor size, tumor apoptosis, and side effects were measured in glioma-bearing rat model. The results showed that EMP exposure could enhance the delivery of CCNU to tumor tissue, facilitate tumor apoptosis, and inhibit tumor growth without obvious side effects...
November 6, 2017: Bioelectromagnetics
https://www.readbyqxmd.com/read/29100935/immunomodulatory-effects-of-a-bioactive-fraction-of-strobilanthes-crispus-in-nmu-induced-rat-mammary-tumor-model
#13
Hassan Muhammad Yankuzo, Yusha'u Shu'aibu Baraya, Zulkarnain Mustapha, Kah Keng Wong, Nik Soriani Yaacob
ETHNOPHARMACOLOGICAL RELEVANCE: Strobilanthes crispus Blume is traditionally consumed among local Malay and indigenous communities for the treatment of cancer and other ailments such as gastrointestinal disorders, inflammatory wounds of snake bite and immune system activation amongst others. We previously demonstrated that a bioactive fraction of S. crispus leaves (F3) was cytotoxic to breast cancer cells in vitro and inhibited tumor growth in N-methyl-N-nitrosourea (NMU)-induced breast cancer rat model...
November 1, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29098723/establishing-a-novel-pig-a-gene-mutation-assay-in-l5178ytk-mouse-lymphoma-cells
#14
Yiying Wang, Javier Revollo, Page McKinzie, Mason G Pearce, Azra Dad, Berran Yucesoy, Hans Rosenfeldt, Robert H Heflich, Vasily N Dobrovolsky
The X-linked Pig-a gene encodes an enzyme required for the biosynthesis of glycosyl phosphatidylinositol (GPI) anchors. Pig-a mutant cells fail to synthesize GPI and to express GPI-anchored protein markers (e.g., CD90) on their surface. Marker deficiency serves as a phenotypic indicator of Pig-a mutation in various in vivo assays. Here, we describe an in vitro Pig-a mutation assay in L5178YTk(+/-) mouse lymphoma cells, in which mutant-phenotype cells are measured by flow cytometry using a fluorescent anti-CD90 antibody...
November 2, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29075122/adeno-associated-virus-mediated-neuroglobin-overexpression-ameliorates-the-n-methyl-n-nitrosourea-induced-retinal-impairments-a-novel-therapeutic-strategy-against-photoreceptor-degeneration
#15
Ye Tao, Zhen Yang, Wei Fang, Zhao Ma, Yi Fei Huang, Zhengwei Li
Retinal degeneration (RD) is a heterogeneous group of inherited dystrophies leading to blindness. The N-methyl-N-nitrosourea (MNU)-administered mouse is used as a pharmacologically induced RD animal model in various therapeutic investigations. The present study found the retinal neuroglobin (NGB) expression in the MNU-administered mice was significantly lower than in normal controls, suggesting NGB was correlated with RD. Subsequently, an adeno-associated virus (AAV)-2-mCMV-NGB vector was delivered into the subretinal space of the MNU-administered mice...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29062766/the-reason-for-the-amelioration-of-n-methyl-n-nitrosourea-induced-retinitis-pigmentosa-in-rats-by-hydrogen-rich-saline
#16
Wei-Ming Yan, Tao Chen, Xiao-Cheng Wang, Lin-Song Qi, Guan-Hua Zhao, Guo-Qing Yang, Yi-Fei Ma, Ye Tao, Lei Zhang, Zuo-Ming Zhang
AIM: To investigate the effects of hydrogen-rich saline (HRS) on microglia activation and Sirtuin type 1 (Sirt1) in rats with N-methyl-N-nitrosourea (MNU)-induced retinitis pigmentosa (RP). METHODS: Rats were divided into norm (N) group, model (M) group and HRS (H) group. Rats in M and H groups were given saline and HRS respectively prior to and after administration of MNU. At one day (d1) and d3 afterwards, electroretinogram and histological examination were performed to confirm the effects of HRS on retinal function and structure of MNU-induced RP...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29046478/cinacalcet-corrects-hypercalcemia-in-mice-with-an-inactivating-g%C3%AE-11-mutation
#17
Sarah A Howles, Fadil M Hannan, Caroline M Gorvin, Sian E Piret, Anju Paudyal, Michelle Stewart, Tertius A Hough, M Andrew Nesbit, Sara Wells, Stephen Dm Brown, Roger D Cox, Rajesh V Thakker
Loss-of-function mutations of GNA11, which encodes G-protein subunit α11 (Gα11), a signaling partner for the calcium-sensing receptor (CaSR), result in familial hypocalciuric hypercalcemia type 2 (FHH2). FHH2 is characterized by hypercalcemia, inappropriately normal or raised parathyroid hormone (PTH) concentrations, and normal or low urinary calcium excretion. A mouse model for FHH2 that would facilitate investigations of the in vivo role of Gα11 and the evaluation of calcimimetic drugs, which are CaSR allosteric activators, is not available...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29038934/characterisation-of-fibrosis-in-chemically-induced-rat-mammary-carcinomas-using-multi-modal-endogenous-contrast-mri-on-a-1-5t-clinical-platform
#18
Neil P Jerome, Jessica K R Boult, Matthew R Orton, James A d'Arcy, Ashutosh Nerurkar, Martin O Leach, Dow-Mu Koh, David J Collins, Simon P Robinson
OBJECTIVES: To determine the ability of multi-parametric, endogenous contrast MRI to detect and quantify fibrosis in a chemically-induced rat model of mammary carcinoma. METHODS: Female Sprague-Dawley rats (n=18) were administered with N-methyl-N-nitrosourea; resulting mammary carcinomas underwent nine-b-value diffusion-weighted (DWI), ultrashort-echo (UTE) and magnetisation transfer (MT) magnetic resonance imaging (MRI) on a clinical 1.5T platform, and associated quantitative MR parameters were calculated...
October 16, 2017: European Radiology
https://www.readbyqxmd.com/read/29038003/hemin-supports-the-survival-of-photoreceptors-injured-by-n-methyl-n-nitrosourea-the-contributory-role-of-neuroglobin-in-photoreceptor-degeneration
#19
Ye Tao, Zhao Ma, Bei Liu, Wei Fang, Limin Qin, Yi Fei Huang, Lu Wang, Yanling Gao
Retina is a critical component of the central nerve system that is responsible for the conversion of light stimulus into electrical spikes. Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal dystrophies leading to blindness. We examined retinal neuroglobin (Ngb) expression in a pharmacologically induced RP animal model, the N-Methyl-N-nitrosourea (MNU) administered mice. The retinal Ngb expression in MNU administered mice attenuated following a time dependent manner, suggesting Ngb was involved in the photoreceptor degeneration...
October 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29031729/point-mutation-of-ffar1-abrogates-fatty-acid-dependent-insulin-secretion-but-protects-against-hfd-induced-glucose-intolerance
#20
Sibylle Sabrautzki, Gabriele Kaiser, Gerhard K H Przemeck, Felicia Gerst, Estela Lorza-Gil, Madhura Panse, Tina Sartorius, Miriam Hoene, Susan Marschall, Hans-Ulrich Häring, Martin Hrabě de Angelis, Susanne Ullrich
OBJECTIVE: The fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-dependent augmentation of glucose-induced insulin secretion (GIIS) in pancreatic β-cells. Genetically engineered Ffar1-knockout/congenic mice univocally displayed impaired fatty acid-mediated insulin secretion, but in vivo experiments delivered controversial results regarding the function of FFAR1 in glucose homeostasis and liver steatosis. This study presents a new coisogenic mouse model carrying a point mutation in Ffar1 with functional consequence...
October 2017: Molecular Metabolism
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