The aim of the present study was to investigate the effect of dihydrotanshinone I (DHI) on the survival of human glioma cells and the expression levels of ferroptosis-associated proteins. Human U251 and U87 glioma cells were cultured in vitro and treated with different concentrations of DHI and/or the ferroptosis inhibitor ferrostatin-1. A Cell Counting Kit-8 assay was used to determine the cell survival rate. The cells were further analyzed to determine their 5-, 12-and 15-hydroxyeicosatetraenoic acid (HETE), lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios. Western blotting was used to detect ferroptosis-associated glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthetase 4 (ACSL-4). Changes in the mitochondrial membrane potential (MMP) were also observed using tetramethylrhodamine methyl ester staining and confocal fluorescence microscopy. The results revealed that DHI inhibited the proliferation of human glioma cells. Following treatment of the U251 and U87 cells with DHI, changes in the expression levels of ferroptosis-associated proteins were observed; the expression level of GPX4 decreased and that of ACSL-4 increased. DHI also increased the levels of LDH and MDA in the human glioma cells and reduced the GSH/GSSG ratio. The DHI-treated cells also exhibited a marked reduction in MMP. Furthermore, ferrostatin-1 blocked the DHI-induced effects in human glioma cells. From these results, it may be concluded that DHI inhibits the proliferation of human glioma cells via the induction of ferroptosis.
Our results demonstrated successful chemoprotection against myelosuppression in mice by MDR1-transduced repopulating human hematopoietic cells with an optimized transduction protocol.
OBJECTIVE Infection is one of the important and frequent complications following implantable pulse generator and deep brain stimulation (DBS) electrode insertion. The goal of this study was to retrospectively evaluate and identify potential risk factors for DBS infections. METHODS From January 2015 to January 2021 in Qingdao municipal hospital (training cohort) and The First Affiliated Hospital of the University of Science and Technology of China (validation cohort), the authors enrolled patients with Parkinson disease who had undergone primary DBS placement or implantable pulse generator replacement. The cases were divided into infection or no-infection groups according to the 6-month follow-up. The authors used the logistic regression models to determine the association between the variables and DBS infection. Depending on the results of logistic regression, the authors established a nomogram. The calibration curves, receiver operating characteristic curve analysis, and decision curves were used to evaluate the reliability of the nomogram. RESULTS There were 191 cases enrolled in the no-infection group and 20 cases in the infection group in the training cohort. The univariate logistic regression showed that BMI, blood glucose, and albumin were all significant predictors of infection after DBS surgery (OR 0.832 [p = 0.009], OR 1.735 [p < 0.001], and OR 0.823 [p = 0.001], respectively). In the crude, adjust I, and adjust II models, the three variables stated above were all considered to be significant predictors of infection after DBS surgery. The calibration curves in both training and validation cohorts showed that the predicted outcome fitted well to the observed outcome (p > 0.05). The decision curves showed that the nomogram had more benefits than the "All or None" scheme. The areas under the curve were 0.93 and 0.83 in the training and validation cohorts, respectively. CONCLUSIONS The nomogram included BMI, blood glucose, and albumin, which were significant predictors of infection in patients with DBS surgery. The nomogram was reliable for clinical application.
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