Enzymatically Formed Oxysterols and Cell Death.

The side-chain hydroxylation of cholesterol by specific enzymes produces 24(S)-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, and other products. These enzymatically formed side-chain oxysterols act as intermediates in the biosynthesis of bile acids and serve as signaling molecules that regulate cholesterol homeostasis. Besides these intracellular functions, an imbalance in oxysterol homeostasis is implicated in pathophysiology. Furthermore, growing evidence reveals that oxysterols affect cell proliferation and cause cell death. This chapter provides an overview of the pathophysiological role of side-chain oxysterols in developing human diseases. We also summarize our understanding of the molecular mechanisms underlying the induction of various forms of cell death by side-chain oxysterols.

Vitamin E nomenclature. Is RRR-α-tocopherol the only vitamin E?

It has generally been accepted that vitamin E refers to a group of tocochromanols, α-, ß-, γ-, and δ-tocopherols and the corresponding four tocotrienols. Recently, Azzi and colleagues proposed to restrict the term vitamin E only to RRR-α-tocopherol, not to other tocopherols and tocotrienols (Azzi A et al. Free Radic Biol Med. 2023; 207:178-180. doi: 10.1016/j.freeradbiomed.2023.06.029). The aim of this paper is to express our opinion on the nomenclature of vitamin E based on available scientific data. In our opinion, it would be inappropriate to exclude all the tocochromanols other than RRR-α-tocopherol from the vitamin E group at this stage when the molecular mechanisms showing how vitamin E deficiency causes diseases such as ataxia and how vitamin E prevents/reverses such diseases are not elucidated. Understanding of whole functions of tocochromanols including underlying mechanisms and dynamics is essential before revision of currently accepted definition of vitamin E. The potential roles of γ-tocopherol and tocotrienols are discussed despite whether they are vitamin function should be clarified in the future studies.

Cholesterol is more readily oxidized than phospholipid linoleates in cell membranes to produce cholesterol hydroperoxides.

Cholesterol is an essential component of cell membranes and serves as an important precursor of steroidal hormones and bile acids, but elevated levels of cholesterol and its oxidation products have been accepted as a risk factor for maintenance of health. The free and ester forms of cholesterol and fatty acids are the two major biological lipids. The aim of this hypothesis paper is to address the long-standing dogma that cholesterol is less susceptible to free radical peroxidation than polyunsaturated fatty acids (PUFAs). It has been observed that cholesterol is peroxidized much slower than PUFAs in plasma but that, contrary to expectations from chemical reactivity toward peroxyl radicals, cholesterol appears to be more readily autoxidized than linoleates in cell membranes. The levels of oxidation products of cholesterol and linoleates observed in humans support this notion. It is speculated that this discrepancy is ascribed to the fact that cholesterol and phospholipids bearing PUFAs are localized apart in raft and non-raft domains of cell membranes respectively and that the antioxidant vitamin E distributed predominantly in the non-raft domains cannot suppress the oxidation of cholesterol lying in raft domains which are relatively deficient in antioxidant.

Association of COVID-19 information media, providers, and content with vaccine uptake among Tokyo residents.

To elucidate appropriate ways to induce behavior that prevents the spread of infection, we examined the association between COVID-19 vaccination and COVID-19-related information after more than 85% of the population had been vaccinated. Nonprobability quota sampling was used to recruit 2000 Tokyo residents as participants. The association between previous vaccine uptake and how much people thought they were affected by each of nine media, seven providers, and four content types of information was assessed using an online survey form. Subjective influence was assessed, and order logistic regression analyses were performed. We further calculated standardized partial regression coefficients for the independent variables. The results showed that while people did not think they were strongly affected by any COVID-19 information, significant positive associations between 9 of 20 variables, and significant negative associations between 7 of 20 variables were observed with vaccine uptake. The regression analysis involving the interaction terms between independent variables and sex showed a significant association between vaccine uptake and only daily conversation. Simple slope analysis showed a stronger positive association for females than for males. Regression analysis with interaction terms between each independent variable and age showed a significant association between vaccine uptake and print newspapers, social networking services, prefectural governors, family/relatives, accessibility, side effects, and supply visibility. Simple slope analysis also showed that the positive association between the subjective influence of newspapers and vaccine uptake was observed only for older people (≥69 years), and that of prefectural governors was more significant for older than younger people (≤32 years). In contrast, the trustworthy information provided by family/relatives was positively associated with vaccine uptake only for younger people. These results suggest that careful consideration must be given to the differences in age and sex to provide appropriate information that motivates Tokyo residents to receive vaccination during COVID-19 pandemic.