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      • SCIESCOPUSKCI등재

        Ginsenoside Rd protects cerebral endothelial cells from oxygen-glucose deprivation/reoxygenation induced pyroptosis via inhibiting SLC5A1 mediated sodium influx

        Li, Suping,Yu, Nengwei,Xu, Fei,Yu, Liang,Yu, Qian,Fu, Jing The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.5

        Background: Ginsenoside Rd is a natural compound with promising neuroprotective effects. However, the underlying mechanisms are still not well-understood. In this study, we explored whether ginsenoside Rd exerts protective effects on cerebral endothelial cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and its potential docking proteins related to the underlying regulations. Method: Commercially available primary human brain microvessel endothelial cells (HBMECs) were used for in vitro OGD/R studies. Cell viability, pyroptosis-associated protein expression and tight junction protein degradation were evaluated. Molecular docking proteins were predicted. Subsequent surface plasmon resonance (SPR) technology was utilized for validation. Flow cytometry was performed to quantify caspase-1 positive and PI positive (caspase-1+/PI+) pyroptotic cells. Results: Ginsenoside Rd treatment attenuated OGD/R-induced damage of blood-brain barrier (BBB) integrity in vitro. It suppressed NLRP3 inflammasome activation (increased expression of NLRP3, cleaved caspase-1, IL-1β and GSDMD-N terminal (NT)) and subsequent cellular pyroptosis (caspase-1+/PI + cells). Ginsenoside Rd interacted with SLC5A1 with a high affinity and reduced OGD/R-induced sodium influx and potassium efflux in HBMECs. Inhibiting SLC5A1 using phlorizin suppressed OGD/R-activated NLRP3 inflammasome and pyroptosis in HBMECs. Conclusion: Ginsenoside Rd protects HBMECs from OGD/R-induced injury partially via binding to SLC5A1, reducing OGD/R-induced sodium influx and potassium efflux, thereby alleviating NLRP3 inflammasome activation and pyroptosis.

      • SCIESCOPUSKCI등재

        Ginsenoside compound K reduces ischemia/reperfusion-induced neuronal apoptosis by inhibiting PTP1B-mediated IRS1 tyrosine dephosphorylation

        Suping Li,Jing Fu,Liang Yu,Qian Yu,Nengwei Yu,Fei Xu The Korean Society of Ginseng 2023 Journal of Ginseng Research Vol.47 No.2

        Background: Ginsenoside compound K (CK) stimulated activation of the PI3K-Akt signaling is one of the major mechanisms in promoting cell survival after stroke. However, the underlying mediators remain poorly understood. This study aimed to explore the docking protein of ginsenoside CK mediating the neuroprotective effects. Materials and methods: Molecular docking, surface plasmon resonance, and cellular thermal shift assay were performed to explore ginsenoside CK interacting proteins. Neuroscreen-1 cells and middle cerebral artery occlusion (MCAO) model in rats were utilized as in-vitro and in-vivo models. Results: Ginsenoside CK interacted with recombinant human PTP1B protein and impaired its tyrosine phosphatase activity. Pathway and process enrichment analysis confirmed the involvement of PTP1B and its interacting proteins in PI3K-Akt signaling pathway. PTP1B overexpression reduced the tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) after oxygen-glucose deprivation/reoxygenation (OGD/R) in neuroscreen-1 cells. These regulations were confirmed in the ipsilateral ischemic hemisphere of the rat brains after MCAO/R. Ginsenoside CK treatment reversed these alterations and attenuated neuronal apoptosis. Conclusion: Ginsenoside CK binds to PTP1B with a high affinity and inhibits PTP1B-mediated IRS1 tyrosine dephosphorylation. This novel mechanism helps explain the role of ginsenoside CK in activating the neuronal protective PI3K-Akt signaling pathway after ischemia-reperfusion injury.

      • KCI등재

        Validation Study of the Chinese Version of Addenbrooke’s Cognitive Examination III for Diagnosing Mild Cognitive Impairment and Mild Dementia

        Xiao-Jia Li,Lili Yang,Jia Yin,Nengwei Yu,Fang Ye 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.3

        Background and Purpose There are only a few cognitive screening tests for the Chinesespeaking population, and so this study aimed to validate the Chinese version of Addenbrooke’s Cognitive Examination III (ACE-III) for detecting mild cognitive impairment (MCI) and mild dementia. Its diagnostic accuracy was compared with the Chinese versions of the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Methods The 176 included individuals were divided into 3 groups: mild dementia group, MCI group, and normal control group. MMSE, MoCA, and ACE-III were administered to all participants by researchers who were blinded to the clinical grouping. The receiver operating characteristic (ROC) curves were analyzed. Results ACE-III exhibited good internal consistency and convergent validity. Age and education level significantly influenced the total ACE-III scores. When screening MCI, the area under the ROC curve (AUC) was significantly larger for ACE-III than for MMSE (0.88 vs. 0.72, p<0.05) and MoCA (0.88 vs. 0.76, p<0.05). ACE-III showed higher sensitivity (0.75) and specificity (0.89) than MMSE (0.64 and 0.63, respectively) and MoCA (0.67 and 0.77) at the optimal cutoff score of 88/89. For detecting mild dementia, ACE-III yielded satisfactory sensitivity (0.94) and specificity (0.83) at the optimal cutoff score of 74/75. The AUC of ACE-III was 0.95, which was comparable to those of MMSE (0.95) and MoCA (0.91). In participants with ≥12 years of education, the AUC was significantly larger for ACE-III than for MMSE when detecting MCI (0.90 vs. 0.68, p<0.05) and mild dementia (0.97 vs. 0.90, p<0.05). Conclusions The present study has verified that ACE-III is a reliable and accurate tool for screening MCI and mild dementia in the Chinese-speaking population, and is significantly superior to MMSE and MoCA for detecting MCI.

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