Browsing by Author "Le, Yuan"

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    Epalrestat Stimulated Oxidative Stress, Inflammation, and Fibrogenesis in Mouse Liver
    (Oxford University Press, 2018) Le, Yuan; Chen, Liming; Zhang, Yue; Bu, Pengli; Dai, Guoli; Cheng, Xingguo; Biology, School of Science
    Epalrestat (EPS), an aldose reductase inhibitor, is widely prescribed to manage diabetic neuropathy. It is generally believed that EPS is beneficial to diabetic patients because it can protect endothelial cells, Schwann cells, or other neural cells from oxidative stress. However, several clinical studies revealed that EPS therapy led to liver dysfunction, which limited its clinical applications. Currently, the underlying mechanism by which EPS causes liver dysfunction is unknown. This study aimed to investigate the mechanism responsible for EPS-induced liver injury. In mouse liver, EPS 1) increased oxidative stress, indicated by increased expression of manganese superoxide dismutase, Ho-1, and Nqo1, 2) induced inflammation, indicated by infiltration of inflammatory cells, and induced expression of tumor necrosis factor-alpha, CD11b, and CD11c, as well as 3) predisposed to induce fibrosis, evidenced by increased mRNA and protein expression of early profibrotic biomarker genes procollagen I and alpha-smooth muscle actin, and by increased collagen deposition. In cultured mouse and human hepatoma cells, EPS treatment induced oxidative stress, decreased cell viability, and triggered apoptosis evidenced by increased Caspase-3 cleavage/activation. In addition, EPS increased mRNA and protein expression of cytoglobin in mouse liver, indicating that EPS activated hepatic stellate cells (HSCs). Furthermore, EPS treatment in cultured human HSCs increased cell viability. In summary, EPS administration induced oxidative stress and inflammation in mouse liver, and stimulated liver fibrogenesis. Therefore, cautions should be exercised during EPS therapy.
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    Initial Experience of Applying TWIST Dixon with Flexible View Sharing in Breast DCE-MRI
    (Elsevier, 2016-06) Le, Yuan; Kipfer, Hal D.; Nickel, Dominik M.; Kroeker, Randall; Dale, Brian; Holz, Stephanie P.; Weiland, Elisabeth; Lin, Chen; Department of Radiology and Imaging Sciences, IU School of Medicine
    Introduction We developed a new fast imaging technique with flexible time-resolved angiography with stochastic trajectories (TWIST) view sharing to achieve variable temporal resolution and with flexible echo time Dixon to achieve robust fat suppression and to evaluate its application in breast dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI). Materials and Methods The TWIST-Dixon technique was improved with more flexible view sharing and echo times (TWIST-Dixon-Flex). In a dynamic series, each measurement can be separately prescribed as “full,” “partial,” or “center-only.” The spatial and temporal resolution can then be adjusted throughout the measurements to match the dynamic characteristics of contrast enhancement at different phases. The potential advantages of TWIST-Dixon-Flex were evaluated with 18 clinical breast DCE MRI cases. A mixed-effects analysis of variance (ANOVA) was performed to compare the image quality with that of the conventional images. Results The ANOVA showed that the quality of postcontrast TWIST-Dixon-Flex images was significantly higher than that of the conventional images. The TWIST-Dixon-Flex technique also provided the capability to detect differences in rapid contrast uptake from different regions of the breast tumor, which is not possible with conventional breast DCE-MRI. Conclusion The new TWIST-Dixon-Flex technique provides potentially valuable information about early tumor enhancement, and maintains excellent image quality at peak and postcontrast enhancement. This technique could help overcome the compromise on spatial over temporal resolution in clinical breast imaging.