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https://www.readbyqxmd.com/read/29126840/neuroprotective-effect-of-cannabinoid-receptor-1-antagonist-in-the-mnu-induced-retinal-degeneration-model
#1
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
#2
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
#3
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
#4
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
#5
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...
October 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29098723/establishing-a-novel-pig-a-gene-mutation-assay-in-l5178ytk-mouse-lymphoma-cells
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28985365/zebrafish-cdc6-hypomorphic-mutation-causes-meier-gorlin-syndrome-like-phenotype
#13
Likun Yao, Jing Chen, Xiaotong Wu, Shunji Jia, Anming Meng
Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis...
November 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28970238/hcfc2-is-needed-for-irf1-and-irf2-dependent-tlr3-transcription-and-for-survival-during-viral-infections
#14
Lei Sun, Zhengfan Jiang, Victoria A Acosta-Rodriguez, Michael Berger, Xin Du, Jin Huk Choi, Jianhui Wang, Kuan-Wen Wang, Gokhul K Kilaru, Jennifer A Mohawk, Jiexia Quan, Lindsay Scott, Sara Hildebrand, Xiaohong Li, Miao Tang, Xiaoming Zhan, Anne R Murray, Diantha La Vine, Eva Marie Y Moresco, Joseph S Takahashi, Bruce Beutler
Transcriptional regulation of numerous interferon-regulated genes, including Toll-like receptor 3 (Tlr3), which encodes an innate immune sensor of viral double-stranded RNA, depends on the interferon regulatory factor 1 (IRF1) and IRF2 transcription factors. We detected specific abrogation of macrophage responses to polyinosinic-polycytidylic acid (poly(I:C)) resulting from three independent N-ethyl-N-nitrosourea-induced mutations in host cell factor C2 (Hcfc2). Hcfc2 mutations compromised survival during influenza virus and herpes simplex virus 1 infections...
November 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28964928/evaluation-of-estrogenic-potency-of-a-standardized-hops-extract-on-mammary-gland-biology-and-on-mnu-induced-mammary-tumor-growth-in-rats
#15
Annekathrin M Keiler, Dana Macejova, Birgit M Dietz, Judy L Bolton, Guido F Pauli, Shao-Nong Chen, Richard B van Breemen, Dejan Nikolic, Florian Goerl, Michael H Muders, Oliver Zierau, Günter Vollmer
Supplements with estrogenic activities are intensively investigated as potential alternatives for the treatment of menopausal symptoms. These investigations include studies on their safety regarding potential breast cancer risks. Therefore, the aim of this study was to assess whether or not a standardized hops (Humulus lupulus) extract, containing 0.42% of the estrogenic flavanone, 8-prenylnaringenin, would stimulate growth of methyl-nitrosourea (MNU) induced mammary cancer in ovariectomized (OVX) Sprague-Dawley (SD) rats or would impact on the proliferative activity within the normal mammary gland of Wistar rats...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28945287/comparing-bmd-derived-genotoxic-potency-estimations-across-variants-of-the-transgenic-rodent-gene-mutation-assay
#16
John W Wills, George E Johnson, Hannah L Battaion, Wout Slob, Paul A White
There is growing interest in quantitative analysis of in vivo genetic toxicity dose-response data, and use of point-of-departure (PoD) metrics such as the benchmark dose (BMD) for human health risk assessment (HHRA). Currently, multiple transgenic rodent (TGR) assay variants, employing different rodent strains and reporter transgenes, are used for the assessment of chemically-induced genotoxic effects in vivo. However, regulatory issues arise when different PoD values (e.g., lower BMD confidence intervals or BMDLs) are obtained for the same compound across different TGR assay variants...
September 25, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28943948/analysis-of-the-expression-level-and-methylation-of-tumor-protein-p53-phosphatase-and-tensin-homolog-and-muts-homolog-2-in-n-methyl-n-nitrosourea-induced-thymic-lymphoma-in-c57bl-6-mice
#17
Xueyun Huo, Zhenkun Li, Shuangyue Zhang, Changlong Li, Meng Guo, Jing Lu, Jianyi Lv, Xiaoyan Du, Zhenwen Chen
Tumorigenesis is often caused by somatic mutation or epigenetic changes in genes that regulate aspects of cell death, proliferation and survival. Although the functions of multiple tumor suppressor genes have been well studied in isolation, how these genes cooperate during the progression of a single tumor remains unclear in numerous cases. The present study used N-methyl-N-nitrosourea (MNU), one of the most potent mutagenic nitrosourea compounds, to induce thymic lymphoma in C57BL/6J mice. Subsequently, the protein expression levels of phosphatase and tensin homolog (PTEN), transformation protein 53 and mutS homolog 2 (MSH2) were evaluated concomitantly in the thymus, liver, kidney and spleen of MNU-treated mice by western blotting...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28929374/inhibition-of-gsk-3%C3%AE-activation-protects-sd-rat-retina-against-n-methyl-n-nitrosourea-induced-degeneration-by-modulating-the-wnt-%C3%AE-catenin-signaling-pathway
#18
Baoying Wang, Chenghu Hu, Xiaobei Yang, Fangying Du, Yan Feng, Hongbo Li, Chunhui Zhu, Xiaorui Yu
Retinal degenerative diseases are characterized by photoreceptor cell loss. Photoreceptor cell loss leading to retinal degeneration can be induced by N-methyl-N-nitrosourea (MNU), which was widely used to mimic the pathology. However, the mechanism by which MNU induces photoreceptor cell loss is still largely unknown. The purpose of the present study was to investigate whether phosphorylation of glycogen synthase kinase-3β (p-GSK-3β) is a potent mediator of MNU-induced retinal degeneration and how p-GSK-3β affects the process...
October 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28921690/tissue-specific-and-time-dependent-clonal-expansion-of-enu-induced-mutant-cells-in-gpt-delta-mice
#19
Takafumi Nakayama, Tomoko Sawai, Ikuko Masuda, Shinya Kaneko, Kazumi Yamauchi, Benjamin J Blyth, Yoshiya Shimada, Akira Tachibana, Shizuko Kakinuma
DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment...
October 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28917524/tremor-dominant-kyoto-trdk-rats-carry-a-missense-mutation-in-the-gene-encoding-the-sk2-subunit-of-small-conductance-ca-2-activated-k-channel
#20
Takashi Kuramoto, Mayuko Yokoe, Naofumi Kunisawa, Kana Ohashi, Takahito Miyake, Yuki Higuchi, Kazuto Yoshimi, Tomoji Mashimo, Miyuu Tanaka, Mitusru Kuwamura, Shuji Kaneko, Saki Shimizu, Tadao Serikawa, Yukihiro Ohno
Tremor dominant Kyoto (Trdk) is an autosomal dominant mutation that appeared in F344/NSlc rats mutagenized with N-ethyl-N-nitrosourea (ENU). In this study, we characterized and genetically analyzed F344-Trdk/+ heterozygous rats. The rats exhibited a tremor that was especially evident around weaning but persisted throughout life. The tremors of F344-Trdk/+ rats were attenuated by drugs effective against essential tremor (ET) but not drugs used to treat Parkinson's disease-related tremor, indicating that the pharmacological phenotype of F344-Trdk/+ rats was similar to human ET...
December 1, 2017: Brain Research
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