Vitamin E comprises eight structurally related isoforms, including α-, β-, γ-, and δ-tocopherols and their corresponding tocotrienols. These isoforms differ in the degree of methylation of the chromanol ring and the saturation of the side chain, structural features that critically influence their bioavailability, antioxidant capacity, and neuroprotective functions. This mini review system­at­ically summarizes recent advances in the antioxidant and neuroprotective roles of vitamin E isoforms, with particular emphasis on their distinct mechanisms of action in the nervous system. Evidence from cell-based studies, animal models, and human investigations indicates that the neuroprotective effects of vitamin E isoforms vary considerably. Tocotrienols, characterized by their unsaturated side chains, exhibit enhanced membrane mobility and broader biological activity, demonstrating superior neuroprotective properties through modulation of signaling pathways, maintenance of mitochondrial function, and inhibition of abnormal tau hyperphosphorylation. In addition, different tocopherol isoforms show complementary roles in scavenging reactive oxygen species and/or reactive nitrogen species. Despite substantial experimental evidence, clinical data remain limited, and challenges such as differences in bioavailability and incom­plete understanding of isoform-specific mechanisms persist. Overall, vitamin E should be regarded not as a single molecule but as a family of functionally complementary isoforms, whose syner­gistic actions may play a crucial role in maintaining brain health and in the prevention and treatment of neurodegenerative diseases.

This study aimed to investigate the molecular targets and anti-tumor mechanisms of cordycepin in gastric cancer (GC). Bioinfor­matics analysis was performed using the GSE65801 dataset to identify differentially expressed genes (DEGs) in GC. Potential cordycepin targets were screened from the CTD database, and the key gene was identified by intersecting these targets with GC DEGs and constructing a PPI network. The expression of fibro­nectin 1 (FN1) in GC was validated using public databases (TIMER, GEPIA, and UALCAN) and in vitro experiments in GC cell lines (AGS and HGC-27). The functional effects of cordycepin, alone or in combination with FN1 overexpression, on cell proliferation (CCK8 and colony formation assay), apoptosis (flow cytometry), and the ‍PI3K/AKT pathway (Western blot) were assessed. A total of 649 DEGs were identified in GC and 336 potential targets of cordycepin were screened. FN1 was screened as a key intersection target of cordycepin and GC, and was found to be significantly upregulated in GC tissues and cells. High FN1 expression was associated with poor patient survival. Cordycepin treatment significantly inhibited the viability of GC cells and downregulated FN1 protein expression. Functionally, cordycepin suppressed cell proliferation and induced apoptosis by the inhibition of the PI3K/AKT pathway, and these effects were reversed by over­expression of FN1. In conclusion, cordycepin inhibited GC cell growth partially through the downregulation of FN1 and inactivation of the PI3K/AKT pathway, suggesting that FN1 was a novel potential target for cordycepin in the treatment of GC.

Radon inhalation as well as voluntary exercise increase anti­oxidant function in experimental animals. However, the combined effects of radon inhalation and exercise on antioxidant functions have not yet been investigated. In this study, we examined the effects of combined voluntary wheel running (VWR) and radon inhalation on antioxidant functions in various organs of mice. Mice were individually housed in cages equipped with running wheels, and allowed voluntary exercise for 5, 15, or 25 days, followed by radon inhalation at 2,000 Bq/m³ for 24 ‍‍h. Antioxidant function was enhanced by the combined treatment in the kidneys, pancreas, spleen, and stomach, with responses varying according to exercise duration. In contrast, antioxidant function was reduced in the lungs and heart. No clear interaction effects of the combined treatment were observed in the liver, small intestine, colon, and brain. These findings suggest that the combined effects of voluntary exercise and radon inhalation on antioxidant functions are organ-specific and can be categorized into distinct response patterns across tissues.

Triple-negative breast cancer (TNBC) is characterized by its aggres­sive phenotype and limited therapeutic options. FOXO1, a mem­ber of the O-class of forkhead transcription factors, has been impli­cated in various oncogenic processes, yet its specific role in TNBC remains to be fully elucidated. This study aimed to investigate the ‍effects of the FOXO1-selective inhibitor, AS1842856, on the proliferation of the human TNBC cell line MDA-MB-231 and to identify the underlying molecular mechanisms. Treatment with AS1842856 significantly suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner. Additionally, AS1842856 suppressed the expression of lysyl oxidase-like 4 (LOXL4). Given LOXL4 is known to be involved in extracellular matrix remodeling and is frequently associated with cancer progression and metas­tasis, AS8142856 has been considered to suppress MDA-MB-231 cell migration. Interestingly, however, the knockdown of FOXO1 did not lead to a significant reduction in LOXL4 expression levels, suggesting that AS1842856 suppresses LOXL4 expression through FOXO1-independent mechanisms. We found that AS1842856-mediated ERK activation and intracellular reactive oxygen species are crucial in reducing LOXL4. Furthermore, the combined action of pharmacological inhibition of ERK pathways and AS1842856 suppressed MDA-MB-231 cell migration. These findings demon­strate that the ERK-LOXL4 signaling axis may play a critical role in the proliferation of TNBC cells. In conclusion, targeting the LOXL4 and ERK pathways pharmacologically could provide a novel thera­peutic strategy for the treatment of aggressive breast cancers.

Iron deficiency anemia (IDA) remains a prevalent health issue, especially among Japanese women, and may be influenced by dietary patterns and lipid metabolism. This study aimed to investigate the association between circulating bile acid (BA) concentrations and iron-related biomarkers in young Japanese women. Blood biochemical and anthropometric data were collected from 33 healthy young women aged 20. The participants can be divided into two groups based on the levels of total-iron binding capacity (TIBC), although their hemoglobin and ferritin levels were in the normal ranges. When participants were divided based on TIBC, the low TIBC group showed significantly higher levels of 12-hydroxylated, non-12-hydroxylated, and total BAs, as well as significantly lower blood glucose levels compared to the normal group (p<0.05). Positive correlations were observed between TIBC and specific BA species, such as glycolithocholic acid (ρ = 0.3993, p<0.0288), cholic acid (ρ = 0.4767, p<0.0077), and taurocholic acid (ρ = 0.4423, p<0.0144). Additionally, transferrin levels were positively correlated with glycolithocholic acid (ρ = 0.3649, p<0.0474). These findings suggest that TIBC may serve as an early indicator of hypoglycemia, reflecting preclinical metabolic disturbance, in addition to being a latent IDA marker.

We recently reported that flavin-associated compounds such as riboflavin, flavin mononucleotide, and flavin adenine dinucleotide reduce oxidized coenzyme Q and vitamin K homologues to corresponding reduced forms in the presence of reduced β-nicotinamide adenine dinucleotide (NADH). In these processes, coenzyme Q or vitamin K acts as a terminal electron accepter. If oxygen can function as an electron acceptor instead of those quinones, resulting in the formation of superoxide. In this study, superoxide formation from the system of NADH and flavin-associated compounds was examined using a water-soluble tetrazolium salt (WST-1) and 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin-3-one (MCLA) assays. Formation of WST-1 formazan and chemiluminescence from MCLA, both of which are specific to superoxide, increased during co-incubation with NADH and a flavin-associated compound, and significantly suppressed with the addition of superoxide dismutase (SOD). Superoxide is an important reactive oxygen species (ROS) that is converted to other ROS, such as hydrogen peroxide or peroxy­nitrite. HaCaT keratinocytes, immortalized human keratinocytes, were then cultivated with NADH and flavin-associated com­pounds. Cell viability declined with increasing NADH concen­tration but was significantly recovered following the addition of SOD and catalase. We propose a chemical pathway for flavin-associated compound and NADH-induced superoxide generation in vivo, in which extracellular SOD plays an important role in cell survival.