Catalpol Inhibits Autophagy to Ameliorate Doxorubicin-Induced Cardiotoxicity via the AKT-mTOR Pathway.

As a kind of anthracycline, doxorubicin (DOX) is commonly used as an antitumor drug, but its clinical application has been greatly hindered due to its severe cardiotoxicity. Hence, in this study, we investigated the role of catalpol (CTP) and its effect on DOX-induced cardiotoxicity.The cardiac function of mice was evaluated by assessing lactate dehydrogenase, creatine kinase isoenzyme, heart weight to body weight, and heart weight/tibia length levels. Histopathological changes were observed using hematoxylin and eosin staining, and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to examine myocardial apoptosis. Superoxide dismutase (SOD) activity, glutathione (GSH), and malondialdehyde (MDA) levels were measured to confirm the changes in oxidative stress. Western blotting showed the levels of autophagy- and pathway-related proteins. Expression of autophagy marker LC3 was examined using immunofluorescence staining.CTP alleviated DOX-induced cardiac damage in mice. We further observed upregulated SOD and GSH levels, and downregulated MDA level after the CTP treatment in DOX-treated mice, indicating the protective role of CTP against oxidative injury. DOX-induced myocardial apoptosis was also inhibited by CTP treatment in mice. In addition, CTP decreased the levels of Beclin1 and LC3II/LC3I, increased the levels of P62, and activated the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in DOX-treated mice.CTP ameliorated DOX-induced cardiotoxicity by inhibiting oxidative stress, myocardial apoptosis, and autophagy via the AKT-mTOR pathway.

Association between the combined effect of frailty and the estimated glomerular filtration rate and non-elective hospital readmission in elderly inpatients: a cohort study.

BACKGROUND: This study aims to explore the combined effect of frailty and the estimated glomerular filtration rate (eGFR) and non-elective hospital readmission in elderly inpatients. METHODS: A total of 400 elderly patients were selected. The Fried scale was used to assess frailty. The patients were divided into a non-frailty group and a frailty group. They were divided into a normal eGFR group and a eGFR decreased group. Finally, the patients were divided into the following four groups: Group A (no frailty + eGFR normal); Group B (no frailty + eGFR decreased); Group C (frailty + eGFR normal); and Group D (frailty + eGFR decreased). RESULTS: The results of the follow-up survival analysis showed the non-elective hospital readmission within 6 months of discharge. Group A, Group B, Group C, and Group D had an incidence of 21%, 26%, 24%, and 36%, respectively. The Kaplan-Meier curves showed the event-free survival rates of Group A and Group C were higher than that of Group D, and there was no significant difference between Group B and Group D. The risk of non-elective hospital readmission within 6 months in patients with a decreased eGFR was 1.777 times higher than that in patients with a normal eGFR [95% confidence interval (CI): 1.001-3.154], while the risk of non-elective hospital readmission within 6 months in frail patients and non-frail patients did not differ significantly. The multivariate Cox regression analysis showed that the risk of non-elective hospital readmission in Group D was 2.295 times higher than that in Group A (95% CI: 1.096-4.810), and the difference was statistically significant. The risk of non-elective hospital readmission in Group B was 1.401 times of that in Group A (95% CI: 0.665-2.953), while that in Group C was 91.8% (95% CI: 0.403-2.092), but the differences were not statistically significant. CONCLUSIONS: A decline in eGFR is associated with non-elective hospital readmission in elderly inpatients within 6 months; however, frailty is not associated with non-elective hospital readmission. The combined effect of frailty and eGFR in elderly inpatients is related to non-elective hospital readmission.