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        Assessment of the Cytotoxic and Apoptotic Effects of Chaetominine in a Human Leukemia Cell Line

        Yao, Jingyun,Jiao, Ruihua,Liu, Changqing,Zhang, Yupeng,Yu, Wanguo,Lu, Yanhua,Tan, Renxiang The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.2

        Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an $IC_{50}$ value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.

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        Improvement of Fumigaclavine C Production in a Two-stage Culture of Aspergillus fumigatus with Molasses as a Cost-effective Ingredient

        Yi-Xiang Zhu,WEIWEI HUAN,Ling-yun Yao,Wan-Guo Yu,Ruihua Jiao,Yan-Hua Lu,Renxiang Tan 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.6

        Fumigaclavine C (FC), which is produced by Aspergillus fumigatus, is a conidiation-associated ergot alkaloid with significant medical benefits. However, its application is restricted by low yields from submerged cultures. In this study, the technical feasibility of using molasses as a cost-effective ingredient for FC production in a two-stage culture of A. fumigatus was evaluated. The results indicated that molasses supplementation significantly enhanced FC accumulation by promoting conidiation and up-regulating hydroxymethylglutaryl-CoA reductase activity. Via the optimization of the two-stage process in the presence of molasses, FC production in shake flasks reached 226.9 mg/L, which was approximately three times that in the original medium (75.9 mg/L). The use of molasses as a cost-effective ingredient for FC fermentation was also successfully reproduced in a lab-scale bioreactor system in which the maximum FC production reached 215.0 mg/L. The FC production obtained in this study is the highest ever reported. This increased efficiency will enable large-scale production of FC and extend the application of molasses as a low-cost substrate for producing other conidiation-related secondary metabolites.

      • KCI등재

        Assessment of the Cytotoxic and Apoptotic Effects of Chaetominine in a Human Leukemia Cell Line

        Jing-Yun Yao,Ruihua Jiao,Changqing Liu,Yupeng Zhang,Wan-Guo Yu,Yan-Hua Lu,Renxiang Tan 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.2

        Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an IC50 value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.

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