ABSTRACT
HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited cell proliferation of multiple cancer cell lines and macrophages, and the anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.
ABSTRACT
Sub-threshold depression refers to a psychological sub-health state that fails to meet the diagnostic criteria for depression. Appropriate intervention can improve the state and reduce the risks of disease development. In this paper, we focus on music neurofeedback stimulation improving emotional state of sub-threshold depression college students.Twenty-four college students with sub-threshold depression participated in the experiment, 16 of whom were members of the experimental group. Decompression music based on spectrum classification was applied to 16 experimental group participants for 10 min/d music neural feedback stimulation with a period of 14 days, and no stimulation was applied to 8 control group participants. Three feature parameters of electroencephalogram (EEG) relative power, sample entropy and complexity were extracted for analysis. The results showed that the relative power of α、β and θ rhythm increased, while δ rhythm decreased after the stimulation of musical nerofeedback in the experimental group. The sample entropy and complexity were significantly increased after the stimulation, and the differences of these parameters pre and post stimulation were statistically significant ( < 0.05), while the differences of all feature parameters in the control group were not statistically significant. In the experimental group, the scores of self-rating depression scale(SDS) decreased after the stimulation of musical nerofeedback, indicating that the depression was improved. The result of this study showed that music neurofeedback stimulation can improve sub-threshold depression and may provides an effective new way for college students to self-regulation of emotion.