Anticancer activity of isoobtusilactone A from Cinnamomum kotoense: involvement of apoptosis, cell-cycle dysregulation, mitochondria regulation, and reactive oxygen species

In this study, we investigate the anticancer effect of isoobtusilactone A (IOA), a constituent isolated from the leaves of Cinnamomum kotoense, on human non-small cell lung cancer (NSCLC) A549 cells. IOA was found to induce the arrest of G2-M phase, induce apoptosis, increase sub-G1, and inhibit the growth of these cells. Further investigation revealed that IOA's blockade of the cell cycle was associated with increased levels of p21/WAF1, p27 (kip1), and p53. In addition, IOA triggered the mitochondrial apoptotic pathway, as indicated by an increase in Bax/Bcl-2 ratios, resulting in a loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of PARP. We also found the generation of reactive oxygen species (ROS) to be a critical mediator in IOA-induced inhibition of A549 cell growth. In antioxidant and NO inhibitor studies, we found that by pretreating A549 cells with either N-acetylcystenine (NAC), catalase, mannitol, dexamethasone, trolox, or L-NAME we could significantly decrease IOA production of ROS. Moreover, using NAC to block ROS, we could significantly suppress IOA-induced antiproliferation, antimigration, and anti-invasion. Finally, we found that IOA inhibited the migration and invasion of A549 cell migration and invasion. Taken together, these results suggest that IOA has anticancer effects on A549 cells.     

Molecular Markers and Prognosis of Myelofibrosis in the Genomic Era: A Meta-analysis

Molecular markers are important in guiding treatment and predicting outcome in the genomic era. Meta-analysis of molecular markers in myelofibrosis through a search of PubMed and Medline through October 31, 2017 was performed. Markers with more than 3 studies that compared overall survival (OS) and leukemia-free survival (LFS) were analyzed. A total of 16 studies were included. Hazard ratios (HRs) for OS were as follows: IDH 2.65 (95% confidence interval [CI], 1.66-4.21), SRSF2 2.12 (95% CI, 1.18-3.79), high-risk myeloma 2.11 (95% CI, 1.70-2.61), ASXL1 1.92 (95% CI, 1.60-2.32), EZH2 1.88 (95% CI, 1.32-2.67), JAK2 1.41 (95% CI, 1.04-1.93) in the univariate analysis and 1.49 (95% CI, 0.42-5.30) in the multivariate analysis. LFS of JAK2 and SRSF2 had HRs of 1.81 (95% CI, 0.42-5.30) and 0.36 (95% CI, 0.02-6.48), respectively. In conclusion, mutations in IDH, SRSF2, and ASXL1 had worse prognosis in OS with HRs around 2. JAK2 and SRSF2 mutation were not associated with increased leukemia transformation. The adverse effect of triple-negative, which was often compared with CALR mutation, needs to be explored.     

Comparison of ultrasound and dorsal tangential view for dorsal cortex screw penetration in volar plating of the distal radius

We compared the accuracy of the fluoroscopic dorsal tangential view (DTV) and an ultrasound (US) examination in detecting dorsal screw penetration during volar distal radius plating. In six fresh cadaveric distal radii, seven periarticular locking screws in two rows for each plate were inserted according to the measured length using a depth gauge and then replaced with another that was 1 and 2 mm longer, respectively. The actual protruded length of each screw was determined using computed tomography (CT) images. The accuracy of US and DTV measurements was determined using the intraclass correlation coefficient (ICC), as both measurements were compared with CT measurements. The ICC of US and DTV was 0.96 and 0.75, respectively, for all screws. After excluding the data for proximal-row screws, the ICC of US remained unchanged at 0.96, and that of DTV improved to 0.86. The ICC of US was significantly higher than that of DTV (p < 0.01). US had a 100% detection rate for screw protrusion of more than 1.0 mm. US examination showed excellent consistency with CT measurements and its accuracy was not affected by screw location. US might thus be a practical tool for detecting dorsal cortex screw penetration during volar distal radius plating.