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      • KCI등재

        The Integrins Involved in Soybean Agglutinin-Induced Cell Cycle Alterations in IPEC-J2

        Pan, Li,Zhao, Yuan,Yuan, Zhijie,Farouk, Mohammed Hamdy,Zhang, Shiyao,Bao, Nan,Qin, Guixin Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.2

        Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase (P < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 (P < 0.05). We successfully identified integrins ${\alpha}2$, ${\alpha}3$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle (P < 0.05). Further analysis indicated that integrin ${\alpha}2$, ${\alpha}6$, and ${\beta}1$ were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.

      • KCI등재

        The Integrins Involved in Soybean Agglutinin-Induced Cell Cycle Alterations in IPEC-J2

        Li Pan,Yuan Zhao,Zhijie Yuan,Mohammed Hamdy Farouk,Shiyao Zhang,Nan Bao,GuiXin Qin 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.2

        Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase (P < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 (P < 0.05). We successfully identified integrins 2, 3, 6, 1, and 4 in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle (P < 0.05). Further analysis indicated that integrin 2, 6, and 1 were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.

      • KCI등재

        Advanced glycation end products promote meniscal calcification by activating the mTOR-ATF4 positive feedback loop

        Yang Sheng,Xie JiaJun,Pan ZhiJie,Guan HongMei,Tu YueSheng,Ye YuanJian,Huang ShouBin,Fu ShiQiang,Li KangXian,Huang ZhiWei,Li XiaoQi,Shi ZhanJun,Li Le,Zhang Yang 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

        The meniscus is vital for maintaining knee homeostasis and function. Meniscal calcification is one of the earliest radiological indicators of knee osteoarthritis (KOA), and meniscal calcification is associated with alterations in biomechanical properties. Meniscal calcification originates from a biochemical process similar to vascular calcification. Advanced glycation end products (AGEs) and their receptors (RAGEs) reportedly play critical roles in vascular calcification. Herein, we investigated whether targeting AGE-RAGE is a potential treatment for meniscal calcification. In our study, we demonstrated that AGE-RAGE promotes the osteogenesis of meniscal cells and exacerbates meniscal calcification. Mechanistically, AGE-RAGE activates mTOR and simultaneously promotes ATF4 accumulation, thereby facilitating the ATF4-mTOR positive feedback loop that enhances the osteogenic capacity of meniscal cells. In this regard, mTOR inhibits ATF4 degradation by reducing its ubiquitination, while ATF4 activates mTOR by increasing arginine uptake. Our findings substantiate the unique role of AGE-RAGE in the meniscus and reveal the role of the ATF4-mTOR positive feedback loop during the osteogenesis of meniscal cells; these results provide potential therapeutic targets for KOA.

      • KCI등재

        Beyond Canonical PROTAC: Biological targeted protein degradation (bioTPD)

        Huifang Wang,Runhua Zhou,Fushan Xu,Kongjun Yang,Liuhai Zheng,Pan Zhao,Guangwei Shi,Lingyun Dai,Chengchao Xu,Le Yu,Zhijie Li,Jianhong Wang,Jigang Wang 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

        Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential to modulate disease associated proteins that have previously been considered undruggable, by employing the host destructionmachinery. The exploration and discovery of cellular degradation pathways, including but not limited toproteasomes and lysosome pathways as well as their degraders, is an area of active research. Since the conceptof proteolysis-targeting chimeras (PROTACs) was introduced in 2001, the paradigm of TPD has been greatlyexpanded and moved from academia to industry for clinical translation, with small-molecule TPD being particularlyrepresented. As an indispensable part of TPD, biological TPD (bioTPD) technologies including peptide-, fusionprotein-, antibody-, nucleic acid-based bioTPD and others have also emerged and undergone significantadvancement in recent years, demonstrating unique and promising activities beyond those of conventional small molecule TPD. In this review, we provide an overview of recent advances in bioTPD technologies, summarize theircompositional features and potential applications, and briefly discuss their drawbacks. Moreover, we present somestrategies to improve the delivery efficacy of bioTPD, addressing their challenges in further clinical development.

      • KCI등재

        Spatial analysis of tuberculosis treatment outcomes in Shanghai: implications for tuberculosis control

        Zhang Jing,Shen Xin,Yang Chongguang,Chen Yue,Guo Juntao,Wang Decheng,Zhang Jun,Lynn Henry,Hu Yi,Pan Qichao,Zhang Zhijie 한국역학회 2022 Epidemiology and Health Vol.44 No.-

        OBJECTIVES: Tuberculosis (TB) treatment outcomes are a key indicator in the assessment of TB control programs. We aimed to identify spatial factors associated with TB treatment outcomes, and to provide additional insights into TB control from a geographical perspective.METHODS: We collected data from the electronic TB surveillance system in Shanghai, China and included pulmonary TB patients registered from January 1, 2009 to December 31, 2016. We examined the associations of physical accessibility to hospitals, an autoregression term, and random hospital effects with treatment outcomes in logistic regression models after adjusting for demographic, clinical, and treatment factors.RESULTS: Of the 53,475 pulmonary TB patients, 49,002 (91.6%) had successful treatment outcomes. The success rate increased from 89.3% in 2009 to 94.4% in 2016. The successful treatment outcome rate varied among hospitals from 78.6% to 97.8%, and there were 12 spatial clusters of poor treatment outcomes during the 8-year study period. The best-fit model incorporated spatial factors. Both the random hospital effects and autoregression terms had significant impacts on TB treatment outcomes, ranking 6th and 10th, respectively, in terms of statistical importance among 14 factors. The number of bus stations around the home was the least important variable in the model.CONCLUSIONS: Spatial autocorrelation and hospital effects were associated with TB treatment outcomes in Shanghai. In highly-integrated cities like Shanghai, physical accessibility was not related to treatment outcomes. Governments need to pay more attention to the mobility of patients and different success rates of treatment among hospitals.

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