Search

Your search keyword '"Wen, Hairuo"' showing total 134 results
Start Over Author "Wen, Hairuo"
134 results on '"Wen, Hairuo"'

7. Genotoxicity and edible safety evaluation of Coreopsis tinctoria Nutt.

Author

HU Yanping, SONG Jie, AO Rui, YANG Ying, and WEN Hairuo

Subjects
coreopsis tinctoria nutt., bacterial reverse mutation test, mouse lymphoma assay, mouse bone marow micronucleus test, genotoxicity, Food processing and manufacture, TP368-456, Nutrition. Foods and food supply, TX341-641
Abstract

ObjectiveTo detect the genotoxicity of Coreopsis tinctoria Nutt.（water extract） and provide research data for its safety evaluation.MethodsThe water extract of Coreopsis tinctoria Nutt. was used as the test substance in bacterial reverse mutation test， mouse lymphoma Assay （MLA） with and without metabolic activation S9； and the powder of Coreopsis tinctoria Nutt. was used in micronucleus test. Ames test based on the plate incorporation method was performed to detect his-/trp- revert mutation capabilities of S．typhimurium TA98， TA100， TA1535， TA1537 and E．coli WP2 uvrA induced under four doses of 1.25， 2.5， 5 and 10 mg/ plate； MLA based on the microporous method was performed to detect the increase of tk-+/- mutation frequency （MF） of L5178Y cells induced by 5 concentrations of 1.5， 2.0， 2.5， 3.0 and 3.5 mg/mL under the treatment condition of ±S9/3 h， and to evaluate the damage effects on the tested cells； for the mouse bone marrow micronucleus test： CD-1 mice were administrated with 900 mg/kg， 1 800 mg/kg and 3 600 mg/kg of the Coreopsis tinctoria Nutt. powder （200 mesh） intragastrically for three times at an interval of 24 h， and the samples were collected by 18-24 h after the last dose. The micronucleated cells in 2 000 polychromatic erythrocytes were counted， and the micronucleated cell rate were calculated.ResultsUnder both conditions absent and present S9， the numbers of the revertants in five strains induced by 1.25~10 mg/dish （equivalent to crude drug： 8.33~66.67 mg/plate） were not significantly increased compared with the negative （solvent） control of sterilized water for injection. The MF induced by 1.5~3.5 mg/mL （equivalent to crude drug： 10~23.33 mg/mL） were significantly increased with a concentration-response relationship， and most of the mutants were in the form of small colony. The T-MF and S-MF induced by 3.0 and 3.5 mg/mL +S9 groups were more than 3 times of the negative control group： the mean micronucleus rates in 900 mg/kg， 1 800 mg/kg and 3 600 mg/kg groups were 0.85±0.58， 1.10±0.97 and 1.45±1.12， respectively， with no significant difference compared with the deionized water negative control group.ConclusionThe water extract of Coreopsis tinctoria Nutt. could significantly increase the mutation frequency of tk+/- gene and led to chromosome damage in L5178Y cells， no matter with or without metabolic activation， suggesting its potential genotoxicity to human.

Published
2022
Full Text
View/download PDF

13. The contribution of the intracellular domains to P2X1 receptor regulation

Author

Wen, Hairuo and Evans, Richard

Subjects
572
Abstract

P2X1 receptors are expressed throughout the body and contribute to a range of physiological process, e.g. thrombosis and smooth muscle tone. The intracellular terminals of the P2X1 receptor have been shown to be involved in channel regulation. The aim of this thesis was to explore the contribution of the intracellular amino and carboxy termini to channel regulation, using concatenation, site-directed mutagenesis and biochemical methods. Trimeric concatenated P2X1 receptors were non-functional.The interactions between the intracellular termini were revealed to be essential for subunit aggregation and channel expression. Subsequently, over 30 cysteine point mutations at both the amino and carboxy domains of the P2X1 receptors were generated and examined by electrophysiological studies with methanethiosulfonate modifications. The conserved TXTXK/R at the amino terminal and the residues around the YXXXK motif at the carboxy terminal were highlighted to be important for channel gating and protein trafficking. Residues close to the P2X1 channel pore were shown to be essential in ion conduction and implied interactions between the conserved regulatory motifs and the channel pore of adjacent residues. Roles of the intracellular domains of P2X1 receptor in regulation by protein kinase were revealed by co-expression of minigenes encoding the sequences of amino/carboxy terminus with WT receptors. The results indicated both amino and carboxy termini contribute to the phorbol ester PMA and GPCR mediated response regulations, and demonstrated the important roles of the conserved TXTXK/R motif and the residues around the YXXXK motif. This research sheds light on the possible interactions between the amino and carboxy termini to P2X1 receptor function. The results will be useful for understanding the intracellular topology and signaling modulation mechanism of P2X1 receptor.

Published
2009

17. Toxicity evaluation of main zopiclone impurities based on quantitative structure–activity relationship models and in vitro tests.

Author

Yin, Jie, Wen, Hairuo, and Chen, Hua

Subjects
STRUCTURE-activity relationships, TOXICITY testing, HIGH performance liquid chromatography, BACTERIAL mutation, EMBRYOS, GENETIC toxicology
Abstract

Toxicity evaluation of main zopiclone impurities can provide a basis for safety assessment and quality standards of zopiclone. In this study, the impurity profile of zopiclone was analyzed using forced degradation and related substances of zopiclone tablets using high‐performance liquid chromatography (HPLC). Furthermore, various quantitative structure–activity relationship (QSAR) models were used to compare the toxicity, especially genotoxicity of two main zopiclone degradation impurities, namely, impurity B and 2‐amino‐5‐chloropyridine. The predictive genotoxicity results were verified using an in vitro bacterial reverse mutation (Ames) test. Meanwhile, using zebrafish embryos as an animal model, zopiclone and its main impurities were analyzed at different concentrations, and their effects on zebrafish development, including embryonic teratogenesis and lethality, were examined. The results showed that impurity B and 2‐amino‐5‐chloropyridine were the main degradation impurities of zopiclone; the latter's content increased with increase in the solution storage time. QSAR prediction and in vitro test results confirmed that both impurity B and 2‐amino‐5‐chloropyridine were non‐mutagenic and classified in the fifth impurity category. According to ICH M7 guidelines, these could be controlled as general non‐mutagenic impurities. The relative toxicity to zebrafish embryo development was the highest for 2‐amino‐5‐chloropyridine, followed by impurity B and zopiclone, and the malformation rate and mortality of embryos were concentration dependent. In conclusion, an increase in the control limit of 2‐amino‐5‐chloropyridine is recommended when the quality standards of zopiclone materials and preparations are revised to ensure safety and quality control. The specific limit value of this impurity should be determined through further evaluation and research. The toxicity of two main degradation impurities, zopiclone impurity B and 2‐amino‐5‐chloropyridine, was evaluated based on quantitative structure–activity relationship models and an in vitro bacterial reverse mutation test. Both impurities could be controlled as general non‐mutagenic impurities. The relative toxicity to zebrafish embryo development was the highest for the 2‐amino‐5‐chloropyridine, followed by impurity B and zopiclone. It is recommended to increase the control limit of 2‐amino‐5‐chloropyridine when the quality standards of zopiclone raw materials and preparations are revised. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

20. Emerging technologies and their impact on regulatory science

Author

Anklam, Elke, primary, Bahl, Martin Iain, additional, Ball, Robert, additional, Beger, Richard D, additional, Cohen, Jonathan, additional, Fitzpatrick, Suzanne, additional, Girard, Philippe, additional, Halamoda-Kenzaoui, Blanka, additional, Hinton, Denise, additional, Hirose, Akihiko, additional, Hoeveler, Arnd, additional, Honma, Masamitsu, additional, Hugas, Marta, additional, Ishida, Seichi, additional, Kass, George EN, additional, Kojima, Hajime, additional, Krefting, Ira, additional, Liachenko, Serguei, additional, Liu, Yan, additional, Masters, Shane, additional, Marx, Uwe, additional, McCarthy, Timothy, additional, Mercer, Tim, additional, Patri, Anil, additional, Pelaez, Carmen, additional, Pirmohamed, Munir, additional, Platz, Stefan, additional, Ribeiro, Alexandre JS, additional, Rodricks, Joseph V, additional, Rusyn, Ivan, additional, Salek, Reza M, additional, Schoonjans, Reinhilde, additional, Silva, Primal, additional, Svendsen, Clive N, additional, Sumner, Susan, additional, Sung, Kyung, additional, Tagle, Danilo, additional, Tong, Li, additional, Tong, Weida, additional, Eijnden-van-Raaij, Janny van den, additional, Vary, Neil, additional, Wang, Tao, additional, Waterton, John, additional, Wang, May, additional, Wen, Hairuo, additional, Wishart, David, additional, Yuan, Yinyin, additional, and Slikker Jr., William, additional

Published
2021
Full Text
View/download PDF

23. Hepatotoxicity of copper sulfide nanoparticles towards hepatocyte spheroids using a novel multi-concave agarose chip method

Author

Jiang, Tianyan, primary, Guo, Haoxiang, additional, Xia, Ya-Nan, additional, Liu, Yun, additional, Chen, Dandan, additional, Pang, Guibin, additional, Feng, Yahui, additional, Yu, Huan, additional, Wu, Yanxian, additional, Zhang, Shaodian, additional, Wang, Yangyun, additional, Wang, Yong, additional, Wen, Hairuo, additional, and Zhang, Leshuai W, additional

Published
2021
Full Text
View/download PDF

39. Assessment of the Pig‐a, micronucleus, and comet assay endpoints in rats treated by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl carbamate.

Author

Chen, Gaofeng, Wen, Hairuo, Mao, Zhihui, Song, Jie, Jiang, Hua, Wang, Weifan, Yang, Ying, Miao, Yufa, Wang, Chao, Huang, Zhiying, and Wang, Xue

Subjects
PHARMACOKINETICS, GENETIC toxicology, DRUG efficacy, BONE marrow, CANCER treatment
Abstract

The utility and sensitivity of the newly developed flow cytometric Pig‐a gene mutation assay have become a great concern recently. In this study, we have examined the feasibility of integrating the Pig‐a assay as well as micronucleus and Comet endpoints into acute and subchronic general toxicology studies. Male Sprague–Dawley rats were treated for 3 or 28 consecutive days by oral gavage with procarbazine hydrochloride (PCZ) or ethyl carbamate (EC) up to the maximum tolerated dose. The induction of CD59‐negative reticulocytes and erythrocytes, micronucleated reticulocytes in peripheral blood, micronucleated polychromatic erythrocytes in bone marrow, and Comet responses in peripheral blood, liver, kidney, and lung were evaluated at one, two, or more timepoints. Both PCZ and EC produced positive responses at most analyzed timepoints in all tissue types, both with the 3‐day and 28‐day treatment regimens. Furthermore, comparison of the magnitude of the genotoxicity responses indicated that the micronucleus and Comet endpoints generally produced greater responses with the higher dose, short‐term treatments in the 3‐day study, while the Pig‐a assay responded better to the cumulative effects of the lower dose, but repeated subchronic dosing in the 28‐day study. Collectively, these results indicate that integration of several in vivo genotoxicity endpoints into a single routine toxicology study is feasible and that the Pig‐a assay may be particularly suitable for integration into subchronic dose studies based on its ability to accumulate the mutations that result from repeated treatments. This characteristic may be especially important for assaying lower doses of relatively weak genotoxicants. Environ. Mol. Mutagen. 60:56–71, 2019. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

40. A high-throughput Bhas 42 cell transformation assay for the determination of the carcinogenicity of three herbal extracts

Author

Pu, Jiang, primary, Wang, Ying, additional, Qi, Naisong, additional, Du, Wenwan, additional, Tan, Xiaoyan, additional, Chen, Gaofeng, additional, Wen, Hairuo, additional, Wang, Xin, additional, Hu, Yanping, additional, Song, Jie, additional, Qiu, Yuwen, additional, Liang, Jinqiang, additional, Fu, Xinlu, additional, Huang, Zhiying, additional, and Wang, Xue, additional

Published
2016
Full Text
View/download PDF

41. The in vivo Pig-a gene mutation assay is applied to study the genotoxicity of procarbazine hydrochloride in Sprague-Dawley rats

Author

Pu, Jiang, primary, Deng, Yuanyuan, additional, Tan, Xiaoyan, additional, Chen, Gaofeng, additional, Zhu, Cong, additional, Qi, Naisong, additional, Wen, Hairuo, additional, Guo, Jun, additional, Wang, Xin, additional, Qiu, Yuwen, additional, Liang, Jinqiang, additional, Fu, Xinlu, additional, Hu, Yanping, additional, Song, Jie, additional, Geng, Xingchao, additional, Wang, Chao, additional, Zhang, Lin, additional, Huang, Zhiying, additional, Li, Bo, additional, and Wang, Xue, additional

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results