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Dose-dependent and combined effects of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine on the survival of retinal ganglion cells in adult hamsters

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Neural Regeneration Research 2012年第10期7卷 725-730页

作者： Yaoyu Li An＇an Yang Tingting Zhu Zhao Liu Siwei You Kwok-Fai So Department of Ophthalmology General Hospital of Beijing Military Region Beijing 100700 China Institute of Neurosciences the Fourth Military Medical University Xi＇an 710032 Shaanxi Province China Department of Anatomy Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong Special Administrative Region China

This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine （L-NA） on the survival of retinal ganglion cells （RGCs） at 1 and 2 weeks after unilateral optic nerve transection in adult hamsters. The left optic nerves of all animals were transected intraorbitally 1 mm from the optic disc and RGCs were retrogradely labeled with Fluorogold before they received different daily dosages of single MK-801 or L-NA as well as daily combinational treatments of these two chemicals. All experimental and control animals survived for 1 or 2 weeks after optic nerve transection. Our results revealed that the mean numbers of surviving RGCs increased and then decreased when the dosage of MK-801 （1.0, 3.0 and 4.5 mg/kg） and L-NA （1.5, 3.0, 4.5 and 6.0 mg/kg） increased at both 1 and 2 weeks survival time points. Daily combinational use of 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA lead to a highest RGC number that was even higher than the sum of the RGC numbers in 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA subgroups at 2 weeks. These findings indicated that both MK-801 and L-NA can protect axotomized RGCs in a dose-dependent manner and combinational treatment of these chemicals possesses a potentiative and protective effect.

关键词： retinal ganglion cells optic nerve transection N-methyl-D-aspartate receptor nitric oxide synthase neuronal survival hamster

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Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters

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World Journal of Gastroenterology 2007年第37期13卷 5003-5008页

作者： Tomomichi Iwaki Kaoru Ishizaki Shuji Kinoshita Hideki Tanaka Atsushi Fukunari Makoto Tsurufuji Teruaki Imada Research Laboratory Ⅲ (Immunology) Pharmaceuticals Research Division Mitsubishi Pharma Corporation Yokohama Japan Pharmacokinetics Laboratory Pharmaceuticals Research Division Mitsubishi Pharma Corporation Chiba Japan Discovery Technology Laboratory Pharmaceuticals Research Division Mitsubishi Pharma Corporation Yokohama Japan

AIM： TO investigate the effects of ursodeoxycholic acid （UDCA） on chenodeoxycholic acid （CDCA）-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS： Liver injury was induced in hamsters by administration of 0.5% （w/w） CDCA in their feed for 7 d. UDCA （50 mg/kg and 150 mg/kg） was administered for the last 3 d of the experiment.RESULTS： At the end of the experiment, serum alanine aminotransferase （ALl） increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid （LCA）. UDCA （50 mg/kg and 150 mg/kg） improved liver histology, with a significant decrease （679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ±35.5 U/ L, respectively, P 〈 0.01） in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION： The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.

关键词： Chenodeoxycholic acid hamster Liver bileacids Ursodeoxycholic acid

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Garbanzo Diet Lowers Cholesterol in hamsters

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Food and Nutrition Sciences 2012年第3期3卷 401-404页

作者： Talwinder S. Kahlon Roberto J. Avena-Bustillos Mei-Chen M. Chiu University of California Davis USA. Western Regional Research Center United States Department of Agriculture Agricultural Research Service (USDA-ARS) Albany USA

The present study was conducted to investigate the effect garbanzo containing diet on cholesterol in hamster fed cholesterol containing high fat diet. It was hypothesized that garbanzo diet would lower cholesterol in hamsters, based on previous observation of the bile acid binding potential of garbanzo. Garbanzo (Cicer arietinum), Bengal gram (Cicer arietinum), lentils (Lens culinaris), soy protein isolate (SPI) or casein (control) diets were fed to hamsters for three weeks. Initial and final animal weights, feed intakes and plasma triglycerides values were similar among all the treatments. Garbanzo containing diet significantly lowered total plasma cholesterol (TC) compared with casein control. There was 17% reduction in low density lipoprotein cholesterol (LDL-C) in hamsters fed the garbanzo diet;this difference was not significant due to high variability in within treatment values. Plasma cholesterol values with lentils diet were similar those with the control diet. Liver lipid and liver cholesterol values with lentils diet were higher than all the other treatments. Data suggest that garbanzo diet has the potential to lower the risk of atherosclerosis and improve human health.

关键词： hamster Lipoproteins Cholesterol HDL LDL Garbanzo Bengal Gram Lentils

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Design,synthesis,and biological evaluation of novel tetrahydroprotoberberine derivatives(THPBs) as proprotein convertase subtilisin/kexin type 9(PCSK9)modulators for the treatment of hyperlipidemia

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1216-1230页

作者： Chenglin Wu Cong Xi Junhua Tong Jing Zhao Hualiang Jiang Jiang Wang Yiping Wang Hong Liu State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy China Pharmaceutical UniversityNanjing 210009China University of Chinese Academy of Sciences Beijing 100049China

Proprotein convertase subtilisin/kexin type 9(PCSK9)modulators may attenuate PCSK9-induced low-density lipoprotein receptor(LDLR)degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol(LDL-C).A novel series of tetrahydroprotoberberine derivatives(THPBs)were designed,synthesized,and evaluated as PCSK9 modulators for the treatment of *** them,eight compounds exhibited excellent activities in downregulatinghepatic PCSK9 expression better than berberine in HepG2 *** addition,five compounds 15,18,22,(R)-22,and(S)-22 showed better performance in the low-density lipoprotein,labeled with 1,1’-dioctadecyl-3,3,3’,3’-tetramethyl-indocarbocyanine perchlorate(Dil-LDL)uptake assay,compared with berberine at the same *** 22,selected for in vivo evaluation,demonstrated significant reductions of total cholesterol(TC)and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic *** exploring of the lipid-lowering mechanism showed that compound 22 promoted hepatic LDLR expression in a dose-dependent manner in HepG2 *** results of human ether-ago-go related gene(hERG)inhibition assay indicated the potential druggability for compound 22,which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia.

关键词： PCSK9 Tetrahydroprotoberberine derivatives Low-density lipoprotein cholesterol Lipid-lowering PCSK9 expression Low-density lipoprotein receptor Total cholesterol Hyperlipidemia hamster

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Characteristics of replication and pathogenicity of SARS-CoV-2 Alpha and Delta isolates

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Virologica Sinica 2022年第6期37卷 804-812页

作者： Xiao-Li Feng Dandan Yu Mi Zhang Xiaohong Li Qing-Cui Zou Wentai Ma Jian-Bao Han Ling Xu Cuixian Yang Wang Qu Zhong-Hua Deng Junyi Long Yanghaopeng Long Mingkun Li Yong-Gang Yao Xing-Qi Dong Jianxiong Zeng Ming-Hua Li Kunming National High-level Biosafety Research Center for Non-Human Primates Center for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunming650107China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming650201China National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunming650107China Department of Infectious Diseases Yunnan Provincial Infectious Diseases HospitalKunming650301China Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciencesand China National Center for BioinformationBeijing100101China University of Chinese Academy of Sciences Beijing100049China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming650201China Kunming College of Life Science University of Chinese Academy of SciencesKunming650204China Yunnan Key Laboratory of Biodiversity Information Kunming Institute of ZoologyChinese Academy of SciencesKunming650201China

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally,from B.1.17(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta) to B.1.1.529(Omicron). The emerging or reemerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics,pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 cells. We utilized both animal models of human ACE2(hACE2)transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.

关键词： SARS-CoV-2 Variants of concern(VOC) Alpha Delta hACE2 transgenic mice hamster

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丝裂霉素C诱发中国仓鼠体外培养细胞姐妹染色单体互换的研究

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Current Zoology 1988年第3期 210-213页

作者：孔志明南京大学环境科学研究所环境生物研究室

本文对不同年龄中国仓鼠各种组织的体外培养细胞姐妹染色单体互换(SCE)频率进行了比较研究。实验结果表明,体外培养细胞的自发SCE频率与动物年龄无关,相同组织细胞经MMC处理后,老龄仓鼠SCE频率比幼龄仓鼠SCE频率明显低。心脏和皮肤细胸... 详细信息

本文对不同年龄中国仓鼠各种组织的体外培养细胞姐妹染色单体互换(SCE)频率进行了比较研究。实验结果表明,体外培养细胞的自发SCE频率与动物年龄无关,相同组织细胞经MMC处理后,老龄仓鼠SCE频率比幼龄仓鼠SCE频率明显低。心脏和皮肤细胸的SCE频率高于肺和尾的SCE频率。

关键词： SCE (sister chromatid exchange) In vitro Chinese hamster Mitomycin C.

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Animal models for SARS-CoV-2 and SARS-CoV-1 pathogenesis,transmission and therapeutic evaluation

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World Journal of Virology 2022年第1期11卷 40-56页

作者： Udhaya Bharathy Saravanan Mayurikaa Namachivayam Rajesh Jeewon Jian-Dong Huang Siva Sundara Kumar Durairajan Department of Microbiology School of Life SciencesCentral University of Tamil NaduTiruvarur 610005India Department of Health Sciences Faculty of Medicine and Health SciencesUniversity of MauritiusReduit 80837Mauritius CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055Guangdong ProvinceChina

There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral *** coronavirus family,which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2,crossed the species barrier and infected humans,causing a global outbreak in the 21st *** humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials,animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of *** ideal animal models should reflect the viral replication,clinical signs,and pathological responses observed in *** animal species should be tested to establish an appropriate animal model to study the disease pathology,transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease *** this context,the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.

关键词： Animal models SARS-CoV-1 SARS-CoV-2 COVID-19 Mice hamster Non-human primates Pathogenesis Transmission Therapeutics

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Spontaneous and Bleomycin-Induced <i>γ</i>H2AX Signals in CHO9 Metaphase Chromosomes

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Advances in Bioscience and Biotechnology 2014年第7期5卷 603-616页

作者： María Vittoria Di Tomaso Silvia Basso Laura Lafon-Hughes Gustavo Saona Beatriz López-Carro Ana Laura Reyes-ábalos Pablo Liddle Environmental Quality Evaluation and Control Service Municipality of Montevideo Montevideo Uruguay Genetics Department Instituto de Investigaciones Biológicas Clemente Estable Montevideo Uruguay

In eukaryotes, a cascade of events named DNA damage response (DDR) has evolved to handle DNA lesions. DDR engages the recruitment of signaling, checkpoint control, repair and chromatin remodeling protein complexes, allowing cell cycle delay, DNA repair or induction of apoptosis. An early DDR event involves the phosphorylation of the histone variant γH2AX on serine 139 (H2AX139 phosphorylation) originating the so-called γH2AX. DDR-related H2AX139 phosphorylation have been extensively studied in interphase nuclei. More recently, γH2AX signals on mitotic chromosomes of asynchronously growing cell cultures were observed. We performed a quantitative analysis of γH2AX signals on γH2AX immunolabeled cytocentrifuged metaphase spreads, analyzing the γH2AX signal distributions of CHO9 chromosomes harboring homologous regions both in control and bleomycin (BLM)-treated cultures. We detected γH2AX signals in CHO9 chromosomes of controls which significantly increase after BLM-exposure. γH2AX signals were uniformly distributed in chromosomes of controls. However, the γH2AX signal distribution in BLM exposed cells was significantly different between chromosomes and among chromosome regions, with few signals near the centromeres and a tendency to increase towards the telomeres. Interestingly, both basal and BLM-induced γH2AX signal distribution were statistically equal between CHO9 homologous chromosome regions. Our results suggest that BLM exerts an effect on H2AX139 phosphorylation, prevailing towards acetylated and gene-rich distal chromosome segments. The comparable H2AX139 phosphorylation of homologous regions puts forward its dependence on chromatin structure or function and its independence of the position in the karyotype.

关键词： H2AX Phosphorylation on Serine 139 γH2AX Signals Metaphase Chromosomes Homologous Chromosome Regions CHO9 Chinese hamster Cell Line

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用原位缺日翻译法比较两种细胞死亡的DNA状态

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解剖学报 1994年第2期 207-207页

作者：牛建昭小路武彦中根一穗北京中医药大学组织学胚胎学教研室

用原位缺日翻译法比较两种细胞死亡的ＤＮＡ状态（北京中医药大学组织学胚胎学教研室．北京１０００２９牛建昭，小路武彦，中根一穗）ＤＮＡ断裂存在于不同细胞周期中（增殖、分化、死亡）。为研究不同组织细胞核内ＤＮＡ链切断（ＤＳ... 详细信息

用原位缺日翻译法比较两种细胞死亡的ＤＮＡ状态（北京中医药大学组织学胚胎学教研室．北京１０００２９牛建昭，小路武彦，中根一穗）ＤＮＡ断裂存在于不同细胞周期中（增殖、分化、死亡）。为研究不同组织细胞核内ＤＮＡ链切断（ＤＳＢ），我们采用了缺口翻译法（ＩＮＴ...

关键词： Fibronectin Laminin Neural tube defect Retinoic acid Immunohistochemistry hamster

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