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
Objective@#This study aimed to evaluate the validity and predictive value of different methods for myopia screening, and to provide the most effective method of myopia screening.@*Methods@#A total of 7 441 students of grade 1-12 selected from 36 primary and middle schools in 12 counties in Jiangsu Province were enrolled in this study for ophthalmological examination, and uncorrected visual acuity (UCVA, Plan A), noncycloplegic autorefraction (NCAR, Plan B) and combination of UCVA and NCAR (Plan C) were included in the examination. Receiver operating characteristics (ROC) curve was performed to determine the cut-off values (The gold standard is cycloplegic refraction: SE≤0.5 D), and positive predictive value, sensitivities, specificities and other indicators of three screening tests were compared and calculated.@*Results@#The AUC of the combination test for uncorrected visual acuity(UCVA) and noncycloplegic autorefraction (NCAR) was nearly 1(0.91, 95%CI=0.90-0.92), and the sensitivity, specificity, Yoden index, diagnostic coincidence rate, positive predictive value and negative predictive value were 92.4%，89.5%，0.82，91.1%，91.3%，90.8%, respectively, but the index of the younger pupils in primary schools was relatively low. The result of screening plan A for students of middle and high school students was the closest to that of myopia diagnosis.@*Conclusion@#Combination test, which was recommended by China National Health Commission, can be a practical solution for school students for myopic screening. Under the condition of no mydriatic refraction, Plan A could be considered for myopia screening especially for middle and high school students. For the younger pupils, it is suggested to use the internationally recommended myopia screening strategy, that is, SE ≤ 0.50D after mydriasis.
ABSTRACT
Vascular remodeling is an important pathological link of maintaining and developing high blood pressure. TCM has the advantage of comprehensive regulation effects with multiple channels, multiple links and multiple targets. Applying TCM treatment in vascular remodeling is a good point cut in the prevention and treatment of hypertention. This article reviewed the research status of TCM treatment of vascular remodeling in hypertention, with a purpose to provide ideas for clinical application and further research.
ABSTRACT
Myocardial fibrosis is the pathological basis of hypertensive heart disease, which is the key to control cardiovascular complications. Traditional Chinese medicine (TCM) has the advantage of targeting many components of a system and providing more integrated regulation than modern medicine. While, modern medicine tends to target a single pathological link. This study was aimed to investigate effects and mechanisms in the treatment of myocardial fibrosis in hypertension with TCM from a different perspective, which provided references for clinical treatment.