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Recently, SGI-1027, a well-known inhibitor of DNA-methyl transferases (DNMTs), was reported to effectively reduce formation of pathogenic PrP^(Sc) in prion-infected cells. Herein, we confirm the elimination of PrP^(Sc) in chronic wasting disease (CWD) prion-infected neurons by SGI-1027, and pinpoint the binding region of human prion protein to SGI-1027. SGI-1027 is broadly functional against various prion disease types, including human prions. Previously, the inhibitory effects of SGI-1027 on DNMT function is well tested in various cell culture models. While neither treatment with a DNMTs enhancer S-adenosyl-L-methionine (SAM), nor with their inhibitor, 5-azacytidine, prevented PrP^(Sc) propagation, SGI-1027 did. Our study suggest that the anti-prion effects of SGI-1027 are a result of its direct interaction with PrP^(C), which effectively interferes with the pathogenic conformational change of PrP^(C) to PrP^(Sc). We conclude that SGI-1027 driven suppression of pathogenic PrP^(Sc) is independent of DNMT.

The upregulation of dopaminergic neuronal differentiation is necessary for stem cell therapy in Parkinson's disease (PD). In this study, neuronal differentiation efficiency increased by more than 2 times in P19 embryonic stem cells (ESCs) induced by N-acetylcysteine (NAC) and retinoic acid (RA) as compared to RA alone, with suppressed glial differentiation. The majority of NAC-treated stem cells grafted into brains of PD mice differentiated into dopaminergic neurons and persisted well for 6 weeks. Parkinsonism was also greatly improved after grafting NAC-treated cells in comparison to cells treated with only RA. Our results strongly suggest that NAC treatment may be an effective strategy for generating stem cells fated to become dopaminergic neurons for PD clinical therapy.

Non-refined soybean oil was heated for 4 hours at 180 degrees C together with moistened starch or casein. The total tocopherol and individual isomers were determined. Under experimental conditions described there was a considerable loss of tocopherols (49% of the initial amount). The loss of alpha-isomer is regarded to be the most essential from the physiological standpoint. Introduction of carbohydrates (e.g. starch) to the heated oil maked the tocopherol content descend 39.4%, whereas that of proteins (e.g. casein) resulted in a 34.6%-decrease. The product heated in the oil had a selective action on the isomeric composition of tocopherols. Starch heating resulted in a decrease of gamma-isomer losses, casein heating produced the same effect. However, alpha-isomer losses increased. The data obtained indicate the necessity of discounting tocopherol losses on thermal treatment while appraising different culinary dishes and products as vitamin E source in nutrition.