Melatonin reverses nasopharyngeal carcinoma cisplatin chemoresistance by inhibiting the Wnt/ß-catenin signaling pathway.

Cisplatin (DDP)-based concurrent chemo-radiotherapy is a standard approach to treat locoregionally advanced nasopharyngeal carcinoma (NPC). However, many patients eventually develop recurrence and/or distant metastasis due to chemoresistance. In this study, we aimed to elucidate the effects of melatonin on DDP chemoresistance in NPC cell lines in vitro and vivo, and we explored potential chemoresistance mechanisms. We found that DDP chemoresistance in NPC cells is mediated through the Wnt/ß-catenin signaling pathway. Melatonin not only reversed DDP chemoresistance, but also enhanced DDP antitumor activity by suppressing the nuclear translocation of ß-catenin, and reducing expression of Wnt/ß-catenin response genes in NPC cells. In vivo, combined treatment with DDP and melatonin reduced tumor burden to a greater extent than single drug-treatments in an orthotopic xenograft mouse model. Our findings provide novel evidence that melatonin inhibits the Wnt/ß-catenin pathway in NPC, and suggest that melatonin could be applied in combination with DDP to treat NPC.

The Value of Index of Microvascular Resistance Measured Before and Following Percutaneous Coronary Intervention in Predicting Perioperative Myocardial Infarction in Patients With Stable Coronary Artery Disease / 中国循环杂志

Objectives: This study was designed to assess whether measurement of the index of microvascular resistance (IMR) before and following percutaneous coronary intervention (PCI) could help identify patients who develop periprocedural myocardial infarction (PPMI). Methods: 54 patients with stable coronary artery disease undergoing elective PCI were divided into PPMI group and no-PPMI group. IMR and FFR was measured before and following percutaneous coronary intervention (PCI) with a pressure wire. Times of balloon inflation was also analyzed. hs-TnI at 24 h post PCI was measured. rPIMR value was calculated. Results: IMR obtained at pre-PCI and post-PCI as well as rPIMR were significantly higher in PPMI patients than in no-PPMI patients (22.02±2.92 vs 17.46±3.44, 25.86±3.04 vs 18.96±2.84, 1.22±0.21 vs 0.94±0.24, all P<0.05, respectively). Patients with PPMI more frequently underwent pre- and post-dilatation(70.8% vs 36.7%, 54.2% vs 23.3%, P<0.05), respectively, the number of balloon inflations was significantly higher in patients with PPMI than in no-PPMI patients (4.33±1.79 vs 3.20±1.63, P<0.05). The area under the ROC curve for predicting PPMI event by pre-PCI IMR was 0.941 (95%CI: 0.884-0.998, P<0.05), cut-off value was 19.91 (sensitivity: 95.8% and specificity: 77.0%). Multivariate logistic analysis showed that pre- and post-PCI IMR, rPIMR were positively correlated with PPMI (all P<0.05). Conclusions: Measuring IMR and rPIMR may allow prospective identification of patients at increased risk of PPMI.

Screening, Identification and Fermentation Optimization of Aminotransferase-producing Strain / 微生物学通报

A strain named as WJ44 with capability of producing branched-chain aminotransferase was isolated from the soil, the enzyme activity is especially high when used leucine as a substrate. According to the physiological characteristics, biochemical characteristics and 16S rRNA sequence of WJ44, the strain was identified as Bacillus cereus. The optimal carbon source and nitrogen source were also determined as 20 g/L glucose, 15 g/L tryptone and 5 g/L beef extract, respectively. The optimal proportion of other component in the medium is corn steep liquor 15 g/L, KH2PO4 3 g/L, MgSO4?7H2O 0.5 g/L. The optimum original pH value is 7.0, the cultural temperature is 37℃, liquid volume is 20 mL/250 mL, the shaker’s rotating speed is 200 r/min. The highest leucine transferase activity of 45.787 U/mL was achieved after 10 h under the opti- mal condition, and the dry weight of cell is 8.643 g/L, increased by 54% and 10% respectively. This result shows that WJ44 is a branched-chain aminotransferase-production strain with fine capability.