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      • SCIESCOPUSKCI등재

        Target engagement of ginsenosides in mild cognitive impairment using mass spectrometry-based drug affinity responsive target stability

        Zhu, Zhu,Li, Ruimei,Qin, Wei,Zhang, Hantao,Cheng, Yao,Chen, Feiyan,Chen, Cuihua,Chen, Lin,Zhao, Yunan The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.6

        Background: Mild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC-MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a proteineprotein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

      • A new reconfigurable liquid-metal-antenna-based sensor

        Xiao-Ping Zhou,Yihui Fu,Hantao Zhu,Zihao Yu,Shanyong Wang 국제구조공학회 2022 Smart Structures and Systems, An International Jou Vol.30 No.4

        In this paper, a new sensor chip with frequency reconstruction range of 2.252 GHz ~ 2.450 GHz is designed and fabricated. On this basis, a self-designed "T-shaped" shell is added to overcome the disadvantage of uneven deformation of the traditional steel shell, and the range of the sensor chip is expanded to 0 kN ~ 96 kN. The liquid metal antenna is used to carry out a step-by-step loading test, and the relationship between the antenna resonance frequency and the pressure load is analyzed. The results show that there is a good linear relationship between the pressure load and the resonant frequency. Therefore, the liquid metal antenna can be regarded as a pressure sensor. The cyclic loading and unloading experiments of the sensor are carried out, and different loading rates are used to explore the influence on the performance of the sensor. The loading and unloading characteristic curves and the influence characteristic curves of loading rate are plotted. The experimental results show that the sensor has no residual deformation during the cycle of loading and unloading. Moreover, the influence of temperature on the performance of the sensor is studied, and the temperature correction formula is derived.

      • SCIESCOPUSKCI등재

        A possible mechanism to the antidepressant-like effects of 20 (S)-protopanaxadiol based on its target protein 14-3-3 ζ

        Chen, Lin,Li, Ruimei,Chen, Feiyan,Zhang, Hantao,Zhu, Zhu,Xu, Shuyi,Cheng, Yao,Zhao, Yunan The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.5

        Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3β activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3β (p-Ser9 GSK 3β), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3β activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3β polypeptide. PPD promoted the binding and subsequently decreased GSK 3β activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3β (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3β kinase activity, thereby activating the plasticity-related CREBeBDNF signaling pathway.

      • KCI등재

        Discovery and validation of PURA as a transcription target of 20(S)-protopanaxadiol: Implications for the treatment of cognitive dysfunction

        Feiyan Chen,Wenjing Zhang,Shuyi Xu,Hantao Zhang,Lin Chen,Cuihua Chen,Zhu Zhu,Yunan Zhao 고려인삼학회 2023 Journal of Ginseng Research Vol.47 No.5

        Background: 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, has prominent benefits for thecentral nervous system, especially in improving learning and memory. However, its transcriptionaltargets in brain tissue remain unknown. Methods: In this study, we first used mass spectrometry-based drug affinity responsive target stability(DARTS) to identify the potential proteins of ginsenosides and intersected them with the transcriptionfactor library. Second, the transcription factor PURA was confirmed as a target of PPD by biolayerinterferometry (BLI) and molecular docking. Next, the effect of PPD on the transcriptional levels of targetgenes of PURA in brain tissues was determined by qRT-PCR. Finally, bioinformatics analysis was used toanalyze the potential biological features of these target proteins. Results: The results showed three overlapping transcription factors between the proteomics of DARTSand transcription factor library. BLI analysis further showed that PPD had a higher direct interaction withPURA than parent ginsenosides. Subsequently, BLI kinetic analysis, molecular docking, and mutations inkey amino acids of PURA indicated that PPD specifically bound to PURA. The results of qRT-PCR showedthat PPD could increase the transcription levels of PURA target genes in brain. Finally, bioinformaticsanalysis showed that these target proteins were involved in learning and memory function. Conclusion: The above-mentioned findings indicate that PURA is a transcription target of PPD in brain,and PPD upregulate the transcription levels of target genes related to cognitive dysfunction by bindingPURA, which could provide a chemical and biological basis for the study of treating cognitive impairmentby targeting PURA.

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