(-)-Epicatechin protects against myocardial ischemia/reperfusion injury via autophagy-dependent ferroptosis.

AIM: (-)-Epicatechin (EPI) has physiological activities such as antioxidant, anti-inflammatory and immune enhancement. In this study, we elucidated the protective effects of EPI in myocardial ischemia/reperfusion injury (MI/RI) and its mechanisms. METHODS: An in vivo I/R model was constructed by performing left anterior descending coronary artery surgery on rats, and an in vitro I/R model was constructed by subjecting hypoxia/reperfusion treatment on H9C2 cells. The damage of cardiac tissues was detected by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (H&E) staining, and expressions of ferroptosis-related proteins were examined by Western blot. Changes in the number of autophagosomes, the levels of oxidative stress and Fe2+ were also examined. RESULTS: EPI reduced abnormal electrocardiogram waveform and infarct size caused by MI/RI in rats. The increasing trend of levels of reactive oxygen species (ROS) and Fe2+ was reversed by EPI, suggesting that EPI can reduce ferroptosis in vivo. Moreover, the levels of lipid ROS and LC3 in H9C2 cells were decreased with EPI treatment, and autophagy and ferroptosis were also alleviated in a dose-dependent manner in vitro. Co-cultivation of USP14 inhibitor IU1 and EPI further revealed that EPI regulates ferroptosis through the USP14-autophagy pathway. CONCLUSIONS: EPI can reduce the level of oxidative stress by promoting USP14 to reduce autophagy, thus inhibiting autophagy dependent ferroptosis and reducing oxidative stress, and has a protective effect on myocardial infarction/myocardial infarction.

Study on high on-aspirin platelet reactivity in diabetic mice based on metabonomics / 中国临床药理学与治疗学

AIM: To explore the underlying mechanism of aspirin-related high on-aspirin platelet reactivity (HAPR) in diabetic state from the perspective of endogenous metabolic changes in metabolomics. METHODS:Type 2 diabetes mellitus (T2DM) mice model was established by the combination treatment of high-fat diet and streptozotocin injections. Mice were randomly divided into Normal group, T2DM group, Normal+aspirin group and T2DM+aspirin group. GC/TOF-MS was used to determine the plasmatic endogenous metabolites of mice. The data were analyzed applying multivariate statistical method. RESULTS:The expression of platelet CD62P and ratio of TXB2/6-keto-PGF1α in the plasma of female T2DM mice showed no significant difference compared with that of the model group. The degree of divergence between normal and normal+aspirin groups was significantly greater than that between T2DM and T2DM+aspirin groups. Biochemical metabolic pathway analysis revealed that HAPR in diabetic mice was linked to glycolysis, gluconeogenesis, pyruvate metabolism, citric acid cycle, ascorbic acid metabolism, and arachidonic acid metabolic pathways. CONCLUSION:The different metabolites obtained in metabolome assay suggests that the HAPR in diabetic state involved several different metabolic pathways, which can better elucidate the biological mechanism of diabetes-associated HAPR.

Titanium dioxide nanoparticles coupled with nuclear localization sequence increases the radiosensitivity of U251 glioma cells / 中华放射医学与防护杂志

Objective To investigate the effects of titanium dioxide ( TiO2 ) nanoparticles coupled with nuclear localization sequence ( NLS ) on the radiosensitivity of U251 glioma cells. Methods Synthesis and characterization of the TiO2-NLS nanoparticles with nuclear targeting property. U251 cells were treated with nanoparticles and/or ionizing radiation. Flow cytometry analysis was performed to measure the ROS content and the cell apoptotic percentage. The DNA damage was detected by using γ-H2AX foci staining. Clonogenic survival assay was used to evaluate the radiosensitivity of U251 cells. Results NLS modification promoted nuclear translocation of TiO2 nanoparticles. Compared with the control nanoparticles, TiO2-NLS treatment increased radiation-induced cell apoptosis (t=8. 96, P<0. 05). Clonogenic survival assay showed the radiosensitization ratios of TiO2 nanoparticle-treated group and TiO2-NLSnanoparticle-treated group were 1. 18 and was 1. 29, respectively. These two ratios had statistically difference ( t =14. 72, P< 0. 05). Conclusions Nuclear targeting TiO2 nanoparticles enhances the radiosensitivity of U251 glioma cells.

Shenmai injection inhibits infIammatory response in IipopoIysaccharides-in-duced septic mice / 中国药科大学学报

This study was to investigate the regulation of lipopolysaccharides(LPS)-induced sepsis in mice by preadministration of Shenmai injection (SMI)and the therapeutic differences between male and female.The females and males were randomly grouped by weight,including control group,LPS-induced sepsis model group and SMI administration group.After preadministration of SMI for 14 days,10 mg/kg LPS were intraperitoneally injected subsequently to induce sepsis.The survival rate of mice,level of serum cytokines and the mRNA expres-sion of proinflammatory cytokines in main tissues were detected to evaluate the impact of SMI in LPS-induced sepsis mice.From the survival rate,which is considered as a gold standard of improvement in sepsis,significant protective effect can be observed after SMI pretreatment in LPS-induced sepsis mice,a more significant effect was shown in the females.Consisting with the serum cytokines levels,SMI significantly inhibited proinflammatory cyto-kines including IL-6,IL-1βand TNF-αmRNA expression in tissues and the regulation of IL-6 was most signifi-cant,which was consistent with the results of ELISA in serum.Moreover,the liver tissue acquired a more evident impact than any other tissues,which fits with the ratio of dry/wet weight.SMI can significantly inhibit inflammato-ry response by delivery in advance in LPS-induced septic mice,providing strong evidence for elaborating mecha-nism in the treatment of cardiovascular disease related inflammation and shock.

Study on therapy of leukemia through proliferated NK cell induced by low-dose radiation in nude mice / 中华放射医学与防护杂志

Objective To separate NK cells of mice from NK cell separation medium and study inhibitory effect of proliferated NK cell induced by low dose radiation on the leukemia model of K562 cells.Methods Flow cytometry and 3H-TdR methods were respectively used to measure proliferation index and activity of NK cells treated with low-dose radiation( which means exposure dose in 20 cGy low LET beam or 5 cGy high LET beam).CD13 + cells were measured by flow cytometry and TNF-α content in blood-serum was detected by ELISA.In vivo,peripheral blood leucocyte count,index of liver,indexes of spleen and kidney were observed in control group and experimental group.Results The purity of NK cell separation was (82.54 ± 0.18)%.The proliferation index of NK cells at 24 hours after 80 mGy irradiated was 36.31 ± 1.32% ,(t =24.69,P ＜0.05).Killing activity of NK cell induced by low dose radiation to K562 cell was (12.59±0.63)%(t=6.63,P＜0.05)and the inhibition ratio was 29.52%.Conclusion The injection of proliferated NK cell induced by low dose radiation demonstrated significant inhibitory effect on the growth of leukemia nude mouse.