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- 저자 : Sundong Lin (검색결과 2 건)
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Sundong Lin,Lechu Yu,Yongqing Ni,Lulu He,Xiaolu Weng,Xuemian Lu,Chi Zhang 대한당뇨병학회 2020 Diabetes and Metabolism Journal Vol.44 No.1
Background: Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study. Methods: Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4´-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months. Results: DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2). Conclusion: FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.
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Sun Dong,Li Xiang,Guo Dajing,Wu Lan,Chen Ting,Fang Zheng,Chen Linli,Zeng Wenbing,Yang Ran 대한영상의학회 2020 Korean Journal of Radiology Vol.21 No.7
Objective: To investigate the value of initial CT quantitative analysis of ground-glass opacity (GGO), consolidation, and total lesion volume and its relationship with clinical features for assessing the severity of coronavirus disease 2019 (COVID-19). Materials and Methods: A total of 84 patients with COVID-19 were retrospectively reviewed from January 23, 2020 to February 19, 2020. Patients were divided into two groups: severe group (n = 23) and non-severe group (n = 61). Clinical symptoms, laboratory data, and CT findings on admission were analyzed. CT quantitative parameters, including GGO, consolidation, total lesion score, percentage GGO, and percentage consolidation (both relative to total lesion volume) were calculated. Relationships between the CT findings and laboratory data were estimated. Finally, a discrimination model was established to assess the severity of COVID-19. Results: Patients in the severe group had higher baseline neutrophil percentage, increased high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and lower baseline lymphocyte count and lymphocyte percentage (p < 0.001). The severe group also had higher GGO score (p < 0.001), consolidation score (p < 0.001), total lesion score (p < 0.001), and percentage consolidation (p = 0.002), but had a lower percentage GGO (p = 0.008). These CT quantitative parameters were significantly correlated with laboratory inflammatory marker levels, including neutrophil percentage, lymphocyte count, lymphocyte percentage, hs-CRP level, and procalcitonin level (p < 0.05). The total lesion score demonstrated the best performance when the data cut-off was 8.2%. Furthermore, the area under the curve, sensitivity, and specificity were 93.8% (confidence interval [CI]: 86.8–100%), 91.3% (CI: 69.6–100%), and 91.8% (CI: 23.0–98.4%), respectively. Conclusion: CT quantitative parameters showed strong correlations with laboratory inflammatory markers, suggesting that CT quantitative analysis might be an effective and important method for assessing the severity of COVID-19, and may provide additional guidance for planning clinical treatment strategies.
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