Amyloid ␤ protein (A␤) elicits a toxic effect on neurons in vitro and in vivo. In present study we attempt to elucidate the mechanism by which A␤ confers its neurotoxicity. The neuroprotective effects of phytoestrogens on A␤-mediated toxicity were also investigated. Cortical neurons treated with 5 M A␤-(25-35) for 40 h decreased the cell viability by 45.5 ؎ 4.6% concomitant with the appearance of apoptotic morphology. 50 M kaempferol and apigenin decreased the A␤-induced cell death by 81.5 ؎ 9.4% and 49.2 ؎ 9.9%, respectively. A␤ increased the activity of caspase 3 by 10.6-fold and to a lesser extent for caspase 2, 8, and 9. The A␤-induced activation of caspase 3 and release of cytochrome c showed a biphasic pattern. Apigenin abrogated A␤-induced cytochrome c release, and the activation of caspase cascade. Kaempferol showed a similar effect but to a less extent. Kaempferol was also capable of eliminating A␤-induced accumulation of reactive oxygen species. These two events accounted for the remarkable effect of kaempferol on neuroprotection. Quercetin and probucol did not affect the A␤-mediated neurotoxicity. However, they potentiated the protective effect of apigenin. Therefore, these results demonstrate that A␤ elicited activation of caspase cascades and reactive oxygen species accumulation, thereby causing neuronal death. The blockade of caspase activation conferred the major neuroprotective effect of phytoestrogens. The antioxidative activity of phytoestrogens also modulated their neuroprotective effects on A␤-mediated toxicity.

Lapatinib, an orally adminstered small-molecule tyrosine kinase inhibitor targeting epidermal growth factor receptors (EGFR) and Her2/Neu, has been widely accepted in the treatment of breast cancer. In this study, we found that lapatinib induced cytotoxicity in human hepatoma Huh7, HepG2 and HA22T cells. For the mode of cell death, we found lapatinib induced a higher percent of dead cells and a lower percent of hypodiploid cells, suggesting non-apoptotic cell death in lapatinib-treated hepatoma cells. Moreover, lapatinib-induced autophagy in hepatoma cells was confirmed by the detection of autophagic LC3-II conversion, the up-regulation of autophagy-related proteins, and the down-regulation of p62 by immunoblotting. Autophagic cell death was demonstrated by images of punctuated LC3 patterns, a higher percent of acridine orange positive cells, as well as a partial rescue of cell death by autophagy inhibitor 3-methyladenine or chloroquine. We also found massive vacuoles in lapatinib-treated hepatoma cells by electronic microscopy. In addition, the shRNA of knocked-down autophagy-related proteins rescued the hepatoma cells from lapatinib-induced growth inhibition. We also demonstrated a reduction of tumorigenesis by lapatinib in vivo. In conclusion, lapatinib induced autophagic cell death and the growth of human hepatoma cells. Our study provides potential cancer therapies by using lapatinib as a treatment for hepatoma.

Fatigue life increased with decreasing reciprocating amplitude in stationary reciprocation. A progressive reciprocating operation with ± 45(o) /10rc/+7(o) motion led to significant fatigue life enhancement and multiple fatigue crack initiation in NiTi endodontic instruments.

All tested soft drinks were found to be erosive. Soft drinks with high calcium contents have significantly lower erosive potential. Low pH value and high citrate content may cause more surface enamel loss. As the erosive time increased, the titratable acidity to pH 7 may be a predictor of the erosive potential for acidic soft drinks. The erosive potential of the soft drinks may be predicted based on the types of acid content, pH value, titratable acidity, and ion concentration.