ABSTRACT
This study aims to present a strategy to transform the worldviews of students, especially college science classrooms, into desirable current worldviews (Darwin, Quantum mechanics, Einstein, refer to Fig 1). Above all, the worldviews, that is metaphysical belief, needs to be changed. This is because metaphysical belief is the basis for the whole framework of conception. Since the previous study emphasized epistemological belief only, an emphasis was placed on metaphysical belief on which epistemological belief is based. Therefore, the two beliefs should be used to elucidate in the education of Nature of Science. Metaphysical belief in the science of cosmic order, symmetry, or disorder is often important in scientific research and can lead to an epistemological view that can select or reject a certain kind of explanation. Specially, the two-slit experiment with single electrons is a radical illustration of another paradigm shift, from classical (mechanistic materialism) to quantum physics (desirable dialectical materialism). The double slit electron experiment creates sensuous images that can be grasped at once. Because quantum mechanics is inherently abstract, it is difficult to accept its meaning.
ABSTRACT
Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 µM) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells.
