Inhibition of glycolysis and SIRT1/GLUT1 signaling ameliorates the apoptotic effect of Leptosidin in prostate cancer cells.

Since the silent information regulation 2 homolog-1 (sirtuin, SIRT1) and glucose transporter 1 (GLUT1) are known to modulate cancer cell metabolism and proliferation, the role of SIRT1/GLUT1 signaling was investigated in the apoptotic effect of Leptosidin from Coreopsis grandiflora in DU145 and PC3 human prostate cancer (PCa) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis, Western blotting, cBioportal correlation analysis, and co-immunoprecipitation were used in this work. Leptosidin showed cytotoxicity, augmented sub-G1 population, and abrogated the expression of pro-poly (ADP-ribose) polymerase (pro-PARP) and pro-cysteine aspartyl-specific protease (pro-caspase3) in DU145 and PC3 cells. Also, Leptosidin inhibited the expression of SIRT1, GLUT1, pyruvate kinase isozymes M2 (PKM2), Hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA) in DU145 and PC3 cells along with disrupted binding of SIRT1 and GLUT1. Consistently, Leptosidin curtailed lactate, glucose, and ATP in DU145 and PC3 cells. Furthermore, SIRT1 depletion enhanced the decrease of GLUT1, LDHA, and pro-Cas3 by Leptosidin in treated DU145 cells, while pyruvate suppressed the ability of Leptosidin in DU145 cells. These findings suggest that Leptosidin induces apoptosis via inhibition of glycolysis and SIRT1/GLUT1 signaling axis in PCa cells.

The importance of tracheostomy to the weaning success in patients with conscious disturbance in the respiratory care center.

BACKGROUND: When to extubate the endotracheal tube is controversial in patients with depressed mental status. The use of the Glasgow Coma Scale (GCS) with score 8 or above as a criterion for extubation by many investigators is questionable. METHODS: A total of 133 consecutive patients (M/F: 86/47; age: 71 ± 17 years) admitted to the respiratory care center (RCC) of the hospital were enrolled. The effects of GCS score on the outcomes and weaning rate of the patients were evaluated. RESULTS: The mortality rate was significantly higher in patients with a GCS score<7T or derived GCS (dGCS) score < 10 (p = 0.011). In patients with a low GCS score (GCS < 7T or dGCS score < 10), the rate of successful ventilator weaning in patients with tracheostomy was significantly higher than that in patients without tracheostomy (GCS and dGCS: 94.4% vs. 38.5%, p = 0.001). However, tracheostomy in patients with a high GCS (GCS score ≥ 7T or dGCS score ≥ 10) did not lead to a higher success rate of weaning. In multivariable analysis, tracheostomy was still an independent determinant of successful weaning in patients with low GCS. CONCLUSION: Tracheostomy increases the success rate of weaning in patients with low GCS, but not in patients with high GCS. Mental status graded by GCS did affect the outcomes in patients with conscious disturbance in the RCC. The low tracheostomy rate in patients with low GCS affected the rate of successful weaning, which might have contributed to the higher mortality rate in patients with low GCS in the RCC.