No abstract

Neuronal oxidative stress (OS) injury has been proven to be associated with many neurodegenerative diseases, and thus, antioxidation treatment is an effective method for treating these diseases. Saikosaponin-D (SSD) is a sapogenin extracted from Bupleurum falcatum and has been shown to have many pharmacological activities. The main purpose of this study was to investigate whether and how SSD protects PC12 cells from HO-induced apoptosis. The non-toxic level of SSD significantly mitigated the HO-induced decrease in cell viability, reduced the apoptosis rate, improved the nuclear morphology, and reduced caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage. Additionally, exogenous HO-induced apoptosis by damaging the intracellular antioxidation system. SSD significantly slowed the HO-induced release of malonic dialdehyde (MDA) and lactate dehydrogenase and increased the activity of superoxide dismutase (SOD) and the total antioxidant capacity, thereby reducing apoptosis. More importantly, SSD effectively blocked HO-induced phosphorylation of extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38MAPK), and specific inhibitors of ERK, JNK, and p38-reduced OS injury and apoptosis, suggesting that SSD reduces OS injury and apoptosis via MAPK signalling pathways. Finally, we confirmed that SSD significantly reduced HO-induced reactive oxygen species (ROS) accumulation, and the ROS inhibitor blocked the apoptosis caused by MAPK activation and cellular oxidative damage. In short, our study confirmed that SSD reduces HO-induced PC12 cell apoptosis by removing ROS and blocking MAPK-dependent oxidative damage.

Let x n = (x 1 , . . . , x n ) and f ∈ R[x n , k]. The problem of finding all k 0 such that f (x n , k 0 ) ≥ 0 on R n is considered in this paper, which obviously takes as a special case the problem of computing the global infimum or proving the semi-definiteness of a polynomial. For solving the problems, we propose a simplified Brown-McCallum's CAD projection operator, Nproj, of which the projection scale is always no larger than that of Brown-McCallum's. For many problems, the projection scale is much smaller than that of Brown-McCallum's. As a result, the lifting phase is also simplified. Some new algorithms based on Nproj for solving those problems are designed and proved to be correct. Comparison to some existing tools on some examples is reported to illustrate the effectiveness of our new algorithms.