Effects of Spironolactone on Hypoxia-Inducible Factor-1α in the Patients Receiving Coronary Artery Bypass Grafting.

ABSTRACT: We explored the protective effect of spironolactone on cardiac function in the patients undergoing coronary artery bypass grafting (CABG) by determining serum hypoxia-inducible factor-1α (HIF-1α) before and after CABG. We used the propensity score matching method retrospectively to select 174 patients undergoing CABG in our hospital from March 2018 to December 2019. Of the 174 patients, 87 patients taking spironolactone for more than 3 months before CABG were used as a test group and other 87 patients who were not taking spironolactone as a control group. In all patients, serum HIF-1α and troponin I levels were determined before as well as 24 hours and 7 days after CABG, serum N-terminal probrain natriuretic peptide (NT-proBNP) level was determined before as well as 12, 24, and 36 hours after CABG, and electrocardiographic monitoring was performed within 36 hours after CABG. The results indicated that there were no significant differences in the HIF-1α level between the test group and the control group before and 7 days after CABG, but the HIF-1α level was significantly lower in the test group than that in the control group 24 hours after CABG (P < 0.01). The 2 groups were not significantly different in the troponin I level at any time point. There was no significant difference in the serum NT-proBNP level between the test group and the control group before CABG, but NT-proBNP (BNP) levels were all significantly lower in the test group than those in the control group at postoperative 12, 24, and 36 hour time points (all P <0.05). The incidence of postoperative atrial fibrillation was also significantly lower in the test group than that in the control group (P = 0.035). Spironolactone protects cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling.

Antigen-loaded nanocarriers enhance the migration of stimulated Langerhans cells to draining lymph nodes and induce effective transcutaneous immunization.

This study aims to investigate the efficacy of chitosan nanoparticles (CS-NPs) as a vehicle for transcutaneous antigen delivery in anti-tumor therapy. Ovalbumin (OVA) or gp100 (melanocyte-associated antigen gp100 protein)-loaded CS-sodium tripolyphosphate (TPP)-grafted NPs were prepared by crosslinking low-molecular-weight CS with TPP. Compared with the FITC-OVA solution, the encapsulated fluorescein isothiocyanate (FITC)-OVA-loaded NPs expressed much stronger cellular uptake ability in vitro and higher ability to migrate to lymph nodes in vivo. After transcutaneous administration, OVA-loaded NPs, with imiquimod as an adjuvant, increased the anti-OVA immunoglobulin G titer to levels similar to those induced by the OVA solution. The gp100-loaded NPs promoted the survival of tumor-bearing mice. These results provided evidence of CS-NPs as promising carriers for transcutaneous vaccine delivery, partly contributing to the increased uptake of NPs by skin antigen-presenting cells as well as their enhanced migration to the surrounding lymph nodes. FROM THE CLINICAL EDITOR: In this study the efficacy of chitosan nanoparticle based vehicles for transcutaneous antigen delivery is investigated in anti-tumor therapy. Authors demonstrate that such nanoparticles may be efficient carriers partly due to their increased uptake by antigen-presenting cells in the skin and their enhanced migration to surrounding lymph nodes.

Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is believed to be the critical process in malignant tumor invasion and metastases, and has a great influence on improving the survival rate in non-small-cell lung cancer (NSCLC) patients. Recent studies suggested that eukaryotic initiation factor 5A-2 (eIF5A-2) might serve as an adverse prognostic marker of survival. We detected eIF5A-2 in NSCLC A549 cells, and found that the invasive capability correlates with the eIF5A-2 expression. METHODS: Transforming growth factor (TGF)-ß1 was used to induce EMT in A549 cells. Western blotting, immunofluorescence, wound healing assay, and transwell-matrigel invasion chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of eIF5A-2. We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence. We tested the change of migration and invasion capabilities of A549 cells by the wound healing assay and transwell-matrigel invasion chambers. RESULTS: After stimulating with TGF-ß1, almost all A549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities. These cells also had higher eIF5A-2 protein expression. Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly. CONCLUSIONS: The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells, which correlated with enhanced tumor invasion and metastatic capabilities. Furthermore, in the A549 cell line, the process of EMT phenotype change could be reversed by eIF5A-2 siRNA, with a consequent weakening of both invasive and metastatic capabilities.