Objective To investigate the changes and roles of hypoxia inducible factor 1?(HIF 1?) expression in myocardial tissues in rats following severe scald. Methods Male Wistar rats inflicted with 40% TBSA Ⅲ degree scald were used as animal models. HIF 1? protein in myocardial tissues was detected by Western blot and immunohistochemical technique. Results HIF 1? protein expression in rat myocardial tissues increased significantly in the early stage following scald. The difference in HIF 1? level between the left and right ventricles was significant. The increased HIF 1? protein was mainly located in the nucleus. Conclusion HIF 1? protein expression in myocardial tissues of rats can be induced by severe scald and HIF 1? protein expression in the left ventricle is significantly higher than that in the right ventricle. The increased HIF 1? protein in the nucleus can induce downstream cytokine expression.

Objective To investigate the roles of mitochondrial DNA (mtDNA) in the respiratory function of cerebral mitochondria in rats exposed to acute hypoxia by observing the changes of mitochondrial respiratory function and cytochrome C oxidase (COX) activity. Methods The rat cerebral cortex mitochondria were isolated by centrifugation. Mitochondrial respiratory function and COX activity were measured by Clark oxygen electrode. Results ① Compared with the control group (C), hypoxia group (H) showed significantly elevated state 4 respiration (ST4), decreased state 3 respiration (ST3), and respiratory control rate (RCR). ② ST3 in group of treatment with chloramphenicol (CAP) plus hypoxia (MH) was significantly lower than that in Group C, while ST4 in Group MH was significantly lower than that in groups C and H. RCR in Group MH was lower than that in Group C, but higher than that in Group H. ③ COX activity in Group H was significantly lower than that in Group C. In Group MH, COX activity was higher than that in Group H, but was still lower than that in Group C. Conclusion The complete expression of mtDNA may play an important role in mitochondrial respiratory function. CAP treatment might be beneficial to the recovery of rat respiratory function.

BACKGROUNDChemoresistance is common among patients with esophageal squamous cell carcinoma (ESCC). We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophageal cancer cell line EC9706.

METHODSThe viability of EC9706 cells exposed to cisplatin was assessed using MTT assay. The times T1, when the number of living cells reached a plateau and T2, when the number of living cells reached a new plateau after the addition of insulin were found. T1 and T2 plateau cells were stained by Annexin V-FITC/PI and monodansylcadaverin (MDC). Fluorescent microscopy was used to observe the expression of apoptosis and autophagy intuitively. Apoptotic ratio and fluorescent intensity were analysed by flow cytometry (FCM) quantitatively. Western blotting analysis was used to estimate the protein expression levels of AKT, mTOR, PI3K, PTEN, autophage related indicator LC3-II and autophage related protein Beclin1 changes that occurred in the course of treatment.

RESULTSA larger number of typical autophagosomes were detected in EC9706 cells exposed to cisplatin. Insulin can increase the apoptosis induced by cisplatin. Apoptotic ratio of T1 plateau cells ((32.6 ± 4.3)%) is significantly less than T2 plateau ((47.5 ± 5.6)%). MDC fluorescent intensity at T1 plateau (104.9 ± 13.2) was significantly higher than intensity at T2 plateau (82.6 ± 10.3). After cotreatment with insulin, the expression level of LC3-II, Beclin1 and PTEN in T2 plateau cells were significantly downregulated, but AKT, mTOR and PI3K expressions significantly upregulated compared with T1 plateau.

CONCLUSIONSInsulin could enhance cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy. The activation of PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of autophagy in EC9706 cells, which may be attributed to the anticancer effects of cisplatin.

Apoptosis ; drug effects ; Autophagy ; drug effects ; Carcinoma, Squamous Cell ; metabolism ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cisplatin ; pharmacology ; Esophageal Neoplasms ; metabolism ; Humans ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects