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        20(S)-Ginsenoside Rh2 displays efficacy against T-cell acute lymphoblastic leukemia through the PI3K/Akt/mTOR signal pathway

        Ting Xia,Jin Zhang,Chuanxin Zhou,Yu Li,Wenhui Duan,Bo Zhang,Min Wang,Jianpei Fang 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.5

        Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

      • KCI등재

        Dimethyl Sulfoxide Suppresses Mouse 4T1 Breast Cancer Growth by Modulating Tumor-Associated Macrophage Differentiation

        Rui Deng,Shi-min Wang,Tao Yin,Ting-hong Ye,Guo-bo Shen, Ling Li,Jing-yi Zhao,Ya-xiong Sang,Xiao-gang Duan,Yu-Quan Wei 한국유방암학회 2014 Journal of breast cancer Vol.17 No.1

        Purpose: The universal organic solvent dimethyl sulfoxide (DMSO)can be used as a differentiation inducer of many cancer cells andhas been widely used as a solvent in laboratories. However, itseffects on breast cancer cells are not well understood. The aimof this study is to investigate the effect and associated mechanismsof DMSO on mouse breast cancer. Methods: We appliedDMSO to observe the effect on tumors in a mouse breast cancermodel. Tumor-associated macrophages (TAMs) were tested byflow cytometry. Ex vivo tumor microenvironment was imitated by4T1 cultured cell conditioned medium. Enzyme-linked immunosorbentassays were performed to detect interleukin (IL)-10 andIL-12 expression in medium. To investigate the cytotoxicity ofDMSO on TAMs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays were performed. Results: We foundthat DMSO produced tumor retardation when injected into mouseperitoneal cavities in a certain concentration range (0.5–1.0 mg/g). Furthermore, as detected by flow cytometry, TAM subtypeswere found to be transformed. We further imitated a tumor microenvironmentin vitro by using 4T1 cultured cell conditionedmedium. Similarly, by using low concentration DMSO (1.0%–2.0% v/v), TAMs were induced to polarize to the classically activatedmacrophage (M1-type) and inhibited from polarizing intothe alternatively activated macrophage (M2-type) in the conditionedmedium. IL-10 expression in tumors was reduced, whileIL-12 was increased compared with the control. Furthermore, wereported that 2.0% (v/v) DMSO could lead to cytotoxicity in peritonealmacrophages after 48 hours in MTT assays. Conclusion:Our findings suggest that DMSO could exert antitumor effects in4T1 cancer-bearing mice by reversing TAM orientation and polarizationfrom M2- to M1-type TAMs. These data may providenovel insight into studying breast cancer immunotherapy.

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        Diversity and geographic variation of endosymbiotic bacteria in natural populations of the pea aphid (Acyrthosiphon pisum) in China

        Zhang Li,Cao Ya,Zhang Li-Jun,Wang Meng-Yao,Wang Xiao-Tong,Yang Xing-Zhuo,Duan Ting-Yu,Yuan Ming-Long 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.3

        Bacterial symbionts in aphids are known to benefit the insect host and associated with aphid’s ecological adaptation. The pea aphid (Acyrthosiphon pisum), an important legume pest worldwide, carries at least eight endosymbionts, providing a model system to study insect–bacteria interactions. However, species diversity and geographic variations of endosymbionts are unknown in Chinese populations; therefore, we characterized symbiont communities and diversity of 27 pea aphid samples from 13 geographic populations of China. Via amplicon high-throughput sequencing and diagnostic PCR, we found that bacterial communities of Chinese populations were dominated by Proteobacteria and Firmicutes. Among eight known endosymbionts, five (Buchnera, Serratia, Hamiltonella, Regiella, and Rickettsia) were detected by both methods, with a specific geographical distribution. The obligate symbiont, Buchnera, was present in all aphid samples, while the four facultative symbionts showed a significant geographic variation. Each population was randomly infected with distinct endosymbionts, ranging from three to five species. Serratia and Rickettsia showed relatively higher abundance in central regions of China, Regiella was predominant in eastern and western China, whereas Ham iltonella showed an extremely low abundance and was absent in four populations. Samples grouped by altitudes showed a significant diversity difference, whereas there was no significant difference between red and green body colors. Bacterial community structures of the Chinese pea aphid populations were mainly influenced by environmental factors, other than body colors. These data can guide the development of potential biocontrol techniques against this aphid.

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