摘要
ObjectiveTo investigate the effect of Shugan Quyu Jiedu prescription (SGQYJDF) on inducing ferroptosis in hepatocellular carcinoma cells based on the tumor protein 53 (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway. MethodMHCC97H cells were divided into the blank serum group (10% blank serum medium), SGQYJDF-containing serum low concentration group (5% SGQYJDF-containing serum and 5% blank serum medium), SGQYJDF-containing serum medium concentration group (7.5% SGQYJDF-containing serum and 2.5% blank serum medium), SGQYJDF-containing serum high concentration group (10% SGQYJDF-containing serum medium) and sorafenib group (sorafenib concentration of 10 μmol·L-1 in 10% blank serum medium). After 24 hours of intervention, the cell survival rate was detected by cell counting kit-8 (CCK-8) assay. The cell proliferation ability was detected by 5-ethynyl-2′-deoxyuridine (EdU) staining. The intracellular ferrous ion (Fe2+) level was detected by ferrous ion fluorescent probe (FerroOrange) staining. The intracellular malondialdehyde (MDA) and glutathione (GSH) levels were detected by colorimetric assays. The ultrastructure of mitochondria was observed by transmission electron microscopy. The expression levels of ferroptosis-related proteins p53, SLC7A11 and GPX4 were detected by Western blot. ResultIn terms of cell viability, compared with the blank serum group, the SGQYJDF group showed a dose-dependent decrease in the survival rate of MHCC97H cells. Effect of the medium and high concentrations of SGQYJDF on the survival rate of MHCC97H cells were significantly decreased (P<0.01). Additionally, the results of the EdU assay showed that both the medium and high concentrations of SGQYJDF were able to inhibit the proliferation ability of MHCC97H cells (P<0.05, P<0.01). Regarding the biochemical indicators of ferroptosis, compared to the blank serum group, the medium and high concentrations of SGQYJDF were able to dose-dependently increase the intracellular Fe2+ level (P<0.01). The low, medium, and high concentrations of SGQYJDF were able to dose-dependently decrease the level of GSH in MHCC97H cells (P<0.01) and increase the level of MDA in the cells (P<0.05, P<0.01). In terms of pathway-related protein expression, compared to the blank serum group, the medium and high concentrations of SGQYJDF could significantly increase the expression of p53 (P<0.01). The low, medium, and high concentrations of SGQYJDF could significantly decrease the expression of GPX4 (P<0.01). The high concentration of SGQYJDF could decrease the expression of SLC7A11 (P<0.01). In terms of the cell morphology of ferroptosis, compared with the blank serum group, transmission electron microscopy revealed that the low concentration of SGQYJDF caused mitochondrial deformation, while the medium and high concentrations of SGQYJDF resulted in reduced mitochondrial volume, increased double-layer membrane density, and decreased mitochondrial cristae. These features were similar to those of sorafenib-induced ferroptosis. Furthermore, compared with the sorafenib group, the high concentration of SGQYJDF showed no statistically significant differences in cell survival rate, proliferation ability, Fe2+ level, MDA level, and GSH level. ConclusionThe results suggest that SGQYJDF may induce ferroptosis and inhibit proliferation in hepatocellular carcinoma MHCC97H cells by upregulating the expression of p53, suppressing the expressions of GPX4 and SLC7A11, downregulating the level of GSH, and leading to the accumulation of intracellular Fe2+ and MDA.
摘要
Objective To analyze whether studying abroad has any influence on clinicians′scientific research ability, and study the rationality of the indicators reflecting the scientific research ability. Methods A total of 36 clinicians who studied abroad more than 3 months between 2008 and 2010 were selected as the abroad group, and the control group of 36 clinicians was selected from the clinician information database of the hospital by the method of Propensity Score Match.A comparison and analysis were made regarding the number of papers(SCI), grants and scientific and technological achievements between the two groups. Meanwhile, covariance analysis was used to compare the difference in the number of scientific research achievements between the two groups.Logistic regression analysis was used to compare the changes in scientific research achievements of clinicians before and after their abroad study. Results The number of articles( SCI) published and grants obtained in the 3 years after going abroad was significantly higher than that of the control group, and the number of grants obtained in the 4-6 years after going abroad was also significantly higher than that in the control group.The number of papers(SCI)published in the three years after going abroad was more than that in the 3 years before going abroad.The number of grants obtained in the 4-6 years after going abroad was more than that in the 3 years before going abroad.These differences were statistically significant. Conclusions Studying abroad has a beneficial effect on the improvement of clinicians′ scientific research ability. It is reasonable and practical to take the number of SCI articles published as the indicator of short-term changes and the number of funds obtained as the indicator of long-term changes in scientific research ability.