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      • KCI등재

        Anti-proliferation and pro-apoptosis effects of miR-582-5p in chronic lymphocytic leukemia via targeting HNRNPA1 and suppression of NF-κB

        Wang Zengsheng,Li Yan,Kuang Xiaochuan,Guo Fang,Lang Tao,Mao Min,Zhang Xiaoyan,Yang Haiqing 대한독성 유전단백체 학회 2021 Molecular & cellular toxicology Vol.17 No.3

        Background MicroRNAs (miRNAs) function as post-transcriptional mediators for genes involved in cancer progression, including chronic lymphocytic leukemia. MiR-582-5p has been identified as a tumor suppressor in various tumors. The antioncogenic role of miR-582-5p was then validated in this study. Objective Mononuclear cells were isolated from peripheral blood samples of patients with chronic lymphocytic leukemia and healthy donors. Expression of miR-582-3p in the mononuclear cells was examined by qRT-PCR. CCK8 assay was performed to detect cell viability, and cell cycle and apoptosis were evaluated by flow cytometry. Dual luciferase activity assay was performed to determine the targeting relationship between miR-582-3p and HNRNPA1, and western blot was performed to unravel the mechanism. Results MiR-582-5p was reduced in mononuclear cells of patients with chronic lymphocytic leukemia compared to healthy donors. Forced miR-582-5p expression reduced cell viability, and promoted apoptosis of chronic lymphocytic leukemia cells. Cell cycle was arrested in G0/G1 phase via miR-582-5p mimic. MiR-582-5p bound to HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1) and down-regulated its expression. Silence of HNRNPA1 decreased cell viability, promoted apoptosis, and blocked cell cycle at G0/G1 phase through up-regulation of IκBα (IkappaBalpha). Moreover, HNRNPA1 silencing attenuated the promotive effect induced by miR-582-5p inhibitor on the progression of chronic lymphocytic leukemia. Conclusion MiR-582-5p demonstrated anti-proliferative and pro-apoptotic roles in chronic lymphocytic leukemia cell growth via down-regulation of HNRNPA1 and up-regulation of IκBα, thus inactivating NF-κB. Background MicroRNAs (miRNAs) function as post-transcriptional mediators for genes involved in cancer progression, including chronic lymphocytic leukemia. MiR-582-5p has been identified as a tumor suppressor in various tumors. The antioncogenic role of miR-582-5p was then validated in this study. Objective Mononuclear cells were isolated from peripheral blood samples of patients with chronic lymphocytic leukemia and healthy donors. Expression of miR-582-3p in the mononuclear cells was examined by qRT-PCR. CCK8 assay was performed to detect cell viability, and cell cycle and apoptosis were evaluated by flow cytometry. Dual luciferase activity assay was performed to determine the targeting relationship between miR-582-3p and HNRNPA1, and western blot was performed to unravel the mechanism. Results MiR-582-5p was reduced in mononuclear cells of patients with chronic lymphocytic leukemia compared to healthy donors. Forced miR-582-5p expression reduced cell viability, and promoted apoptosis of chronic lymphocytic leukemia cells. Cell cycle was arrested in G0/G1 phase via miR-582-5p mimic. MiR-582-5p bound to HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1) and down-regulated its expression. Silence of HNRNPA1 decreased cell viability, promoted apoptosis, and blocked cell cycle at G0/G1 phase through up-regulation of IκBα (IkappaBalpha). Moreover, HNRNPA1 silencing attenuated the promotive effect induced by miR-582-5p inhibitor on the progression of chronic lymphocytic leukemia. Conclusion MiR-582-5p demonstrated anti-proliferative and pro-apoptotic roles in chronic lymphocytic leukemia cell growth via down-regulation of HNRNPA1 and up-regulation of IκBα, thus inactivating NF-κB.

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        Inhibition of Tumor Growth by Recombinant Adenovirus Containing Human Lactoferrin through Inducing Tumor Cell Apoptosis in Mice Bearing EMT6 Breast Cancer

        Jianjie Wang,Qingwang Li,Yetao Ou,Zengsheng Han,Kun Li,Peijun Wang,Shaobo Zhou 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.6

        Human lactoferrin (hLTF), an 80-kDa iron-binding glycoprotein, has antitumor activity. In this study, a recombinant adenovirus containing the human lactoferrin cDNA (ad-rhLTF) was constructed and its effect on tumor growth was investigated in mice bearing EMT6 breast cancer. Ad-rhLTF was injected seven times within 14 days into the tumor site at two concentrations (10^8 and 5 × 10^8 pfu/mL) in mice bearing EMT6 breast cancer. Injected ad-rhLTF had considerable cytotoxicity on mice breast cancer, and significantly reducing the weight of tumor produced and increasing the tumor inhibition rate up to 52.64%. The presence of apoptotic cells was confirmed using TUNEL staining and flow cytometry assays. At the same time, RTPCR and Western blot analyses demonstrated that ad-rhLTF also decreased expression of Bcl-2 and increased Bax and caspase 3 expressions. Therefore, we conclude that ad-rhLTF inhibits tumor growth by inducing tumor cell apoptosis in mice with breast cancer by triggering the mitochondrial-dependent pathway and activation of caspase 3. The results indicate that adrhLTF might be a promising drug for breast cancer gene therapy.

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        Seepage characteristics of the leaching solution during in situ leaching of uranium

        Zeng Sheng,Song Jiayin,Sun Bing,Wang Fulin,Ye Wenhao,Shen Yuan,Li Hao 한국원자력학회 2023 Nuclear Engineering and Technology Vol.55 No.2

        Investigating the seepage characteristics of the leaching solution in the ore-bearing layer during the in situ leaching process can be useful for designing the process parameters for the uranium mining well.We prepared leaching solutions of four different viscosities and conducted experiments using a selfdeveloped multifunctional uranium ore seepage test device. The effects of different viscosities of leaching solutions on the seepage characteristics of uranium-bearing sandstones were examined using seepage mechanics, physicochemical seepage theory, and dissolution erosion mechanism. Results indicated that while the seepage characteristics of various viscosities of leaching solutions were the same in rock samples with similar internal pore architectures, there were regular differences between the saturated and the unsaturated stages. In addition, the time required for the specimen to reach saturation varied with the viscosity of the leaching solution. The higher the viscosity of the solution, the slower the seepage flow from the unsaturated stage to the saturated stage. Furthermore, during the saturation stage, the seepage pressure of a leaching solution with a high viscosity was greater than that of a leaching solution with a low viscosity. However, the permeability coefficient of the high viscosity leaching solution was less than that of a low viscosity leaching solution.

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