Age-related cataracts (ARC) are a leading cause of blindness worldwide, with lens epithelial cell (LEC) senescence playing a key role in their progression. While oxidative stress and DNA damage are known to induce LEC senescence, the mechanisms that actively suppress or delay this process remain poorly understood. The vitamin D receptor (VDR), a nuclear receptor and transcription factor, has been implicated in various physiological processes, including calcium homeostasis, immune modulation, and cell proliferation. Additionally, VDR activation has been reported to protect against cellular aging and oxidative stress. However, the role of VDR in LEC senescence and its potential function in preventing ARC has not been fully elucidated. In this study, we investigated the role of VDR in regulating LEC senescence using the human lens epithelial cell line SRA01/04. VDR knockdown induced senescence markers, including increased SA-β-GAL activity, p21 expression, and γ-H2AX accumulation and reduced Lamin B1 expression. Additionally, VDR knockdown led to a significant increase in intracellular reactive oxygen species (ROS) levels. Conversely, VDR overexpression suppressed H₂O₂-induced senescence and enhanced the expression of antioxidant enzymes such as SOD2 and GPX1. These findings indicate that VDR modulates LEC senescence by regulating oxidative stress and antioxidant enzyme expression, suggesting that VDR may be a potential therapeutic target for ARC prevention. Further studies, particularly in vivo models, are necessary to validate these findings and explore the translational potential of targeting VDR in cataract therapy.

Non-alcoholic fatty liver disease (NAFLD) is influenced by various factors including diet, genetic predisposition, adipocytokines, oxidative stress and endoplasmic reticulum (ER) stress. In this study, we examined how pre-feeding mice a high-fat diet rich in saturated fatty acids (SFAs) affected various indicators of liver disease after administering tunicamycin (TM), an ER stress inducer. We used 4-wk-old male C57BL/6J mice, dividing them into four groups: a normal diet (C), a high-fat diet (F), a normal diet with TM (CT), and a high-fat diet with TM (FT). After 8 wk of feeding, we administered TM intraperitoneally to the CT and FT groups, followed by an anatomical examination 24 h later. TM administration led to increased triglyceride (TG) and cholesterol accumulation in the liver, while significantly lowering TG, cholesterol, and ApoB levels in the plasma. Although liver TG levels were higher in the CT group compared to the FT group, large lipid droplets were present in all individuals only in the FT group. Classic non-alcoholic steatohepatitis markers, such as neutrophil infiltration and hepatocyte ballooning, were not observed. Additionally, plasma alanine aminotransferase activity and expression levels of ER stress-related proteins were significantly higher in the FT group than in the CT or F groups. These findings indicate that combining a high-fat diet rich in SFAs with TM exacerbates ER stress-induced fatty liver disease. This model may be a valuable tool for preclinical trials aimed at addressing ER stress in early-stage NAFLD.

Chronic stress often causes abnormal eating behavior and metabolism due at least in part to the activation of hypothalamic-pituitary-adrenal (HPA) axis resulting in increases glucocorticoids secretion. Cholecystokinin (CCK) is an anorexic gut hormone secreted from enteroendocrine I cells and controls digestion through the gastric emptying and digestive enzyme secretion. In the present study, we highlighted the function of glucocorticoids in CCK-producing cells with enteroendocrine model cell lines and male Wistar rats. We found that glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are expressed in STC-1 cells known as an I cell model line. Synthetic (dexamethasone; DEX) and endogenous (corticosterone; CORT) glucocorticoids reduced CCK transcription in STC-1 cells. Depolarization-induced CCK secretion was attenuated by both glucocorticoids, whereas dietary peptide-induced CCK secretion was enhanced by acute CORT treatment. DEX and CORT treatments weakened phosphorylated signaling pathway for CCK transcription in an agonist-specific manner. Daily single injection of DEX but not CORT for 4 d decreased Cck mRNA in the upper small intestine with altered metabolism and gut glucocorticoid sensitivity in male Wistar rats. These findings provide a new insight to reveal stress-induced abnormal nutrient and metabolic status in relation to gastrointestinal dysfunctions.

This retrospective observational study investigated the association between low vitamin B1 (VB1) levels and cognitive impairment in 77 Japanese patients with Alzheimer’s disease (AD). Multivariable regression analysis identified a significant correlation between low VB1 levels (<2.6 μg/dL) and lower Mini-Mental State Examination (MMSE) scores. Fisher’s exact test demonstrated a strong association between VB1 deficiency and cognitive impairment (p=0.001). Scatter plot analysis supported these findings, illustrating a dose-dependent trend: patients with severe VB1 deficiency consistently exhibited low cognitive function, while those with higher VB1 levels showed better MMSE scores. In contrast, VB12 and folate levels showed no clear association with cognitive function. These results, together with animal studies, suggest that VB1 deficiency may contribute to AD-related neurodegeneration. While benfotiamine, a lipid-soluble VB1 derivative, has been suggested to improve cognition, its causal effect remains uncertain due to the study’s cross-sectional design. Selection bias and the lack of dietary data are also limitations. Further longitudinal research is needed to determine whether VB1 supplementation could help mitigate cognitive decline in AD patients.

Epoxyeicosatrienoic acids (EETs), the epoxidation products of arachidonic acid, were shown to have vasodilation and anti-inflammatory activity in many tissues. In the present study, the roles and mechanisms of EETs in the development of inflammation in adipose tissue were investigated in obese mice. Diet-induced obesity models were established on male C57BL/6 mice, and randomly divided into three groups: OB group (saline), EET group (11,12-EET), or EEZE group (14,15-epoxyeicosa-5(Z)-enoicacid). The levels of cytochrome P450 (CYP) 2J6, hypoxia inducible factor (HIF)-1α, 11,12-EET, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were determined. Angiogenesis was evaluated with platelet endothelial cell adhesion molecule-1 (CD31); Insulin resistance was evaluated with homeostasis model assessment of insulin resistance (HOMA-IR). In diet-induced obese mice, CYP2J6 expression in both mRNA and protein levels was downregulated and 11,12-EET level was reduced, levels of IL-6, IL-1β, TNF-α, and HIF-1α were increased in epididymal adipose tissue and in serum compared with non-obese controls. These changes were attenuated by exogenous 11,12-EET, whereas but aggravated by 14,15-EEZE, an EET antagonist. CD31-positive cells in the epididymal adipose tissue of obese mice were markedly reduced, which was significantly improved by 11,12-EET. HOMA-IR was increased but markedly attenuated by 11,12-EET in obese mice. These findings indicate that dysregulation of the CYP epoxygenases/EETs pathway may contribute to adipose inflammation in diet-induced obese mice. Exogenous EETs may attenuate adipose inflammation through modulation of adipose angiogenesis and hypoxia, which may have a favorable effect on systemic insulin resistance.

Many prospective studies of egg consumption and coronary artery disease (CAD) provided conflicting findings, and ethnicity may influence CAD risk. Two Japanese cohort studies, which were conducted around 1990, reported no significant association between egg consumption and CAD. However, there was no study showing the association between egg consumption and CAD in Japanese patients undergoing coronary angiography (CAG), whose intakes were assessed at the time of CAD diagnosis. The present study is a cross-sectional study to investigate egg intake and CAD in 795 Japanese patients undergoing CAG. Egg intake was classified into 3 categories (<3, 3–4 eggs/wk, and ≥1 egg/d). CAD was found in 506 patients, of whom 299 had multi-vessel disease (MVD). The prevalence of CAD or MVD did not differ markedly among 3 groups of <3, 3–4 eggs/wk, and ≥1 egg/d. Even after adjusting atherosclerotic risk factors and dietary intakes, multivariate analyses showed no significant associations between egg intake and CAD or MVD. Odds ratios (ORs) for 3–4 eggs/wk and ≥1 egg/d compared to <3 eggs/wk was 0.91 (95%CI: 0.62–1.34) and 1.06 (0.67–1.67) for CAD and 0.79 (0.55–1.15) and 1.22 (0.80–1.87) for MVD. However, only among 504 patients without lipid-lowering drugs, patients with 3–4 eggs/wk less often had MVD than those with <3 eggs/wk (p<0.05). In multivariate analyses, ORs for 3–4 eggs/wk and ≥1 egg/d compared to <3 eggs/wk were 0.56 (0.33–0.96) and 1.21 (0.69–2.13) for MVD. Thus, egg consumption was not associated with an increased risk at CAD in Japanese patients undergoing CAG.

Although folate is essential for preconception care and reproductive health, non-invasive and valid methods for screening inadequate dietary folate intake are lacking. Urinary potassium excretion, a recovery biomarker of potassium intake, can be used as a proxy for dietary folate intake if the main sources of dietary folate and potassium are the same. This study examined the accuracy of screening using urinary potassium excretion as a proxy for inadequate dietary folate intake. Participants comprised 104 female university students who completed 3-d weighed food records (3dWFR) and 24-h urine collection on the third day of 3dWFR in April–July between 2019 and 2022. The major sources of dietary folate and potassium were identified, and the correlation coefficients between their intake and urinary potassium excretion were calculated. The area under the curve (AUC) and 95% confidence interval (CI) were calculated using receiver operating characteristic analysis. Vegetables were the food groups that contributed the most to dietary folate intake (42.7%) and potassium intake (28.9%). The correlation coefficient (r=0.57, p<0.001) between dietary folate intake based on the 3dWFR and potassium excretion was almost the same as that between potassium intake and excretion (r=0.63, p<0.001). Urinary potassium excretion could discriminate at ≥100–≥550 μg in 50 μg increments for insufficient dietary folate intake with >0.7 AUC value (and >0.5 lower limit of 95% CI). These findings indicate that urinary potassium excretion can be used as a proxy indicator to screen for individuals with inadequate dietary folate intake.

Completing a full marathon not only causes muscle soreness and fatigue but also increases damage markers in the blood. Supplementary strategies can be used to reduce these effects. In a previous study, we focused on maslinic acid (MA), which reduces pain and suppresses inflammation. This study examined the effects of MA intake in full marathons. Twenty-seven healthy amateur runners (19 males and 8 females) were allocated to either the placebo (Pla) group or the MA group. Owing to one absence and variations in sample collection success, data from 22–26 participants were included in the final analyses depending on the outcome measure. Subjective muscle soreness and fatigue were assessed using a numerical rating scale (0–10), and blood samples were collected at three time points: before the race (Pre), immediately after the race (Post), and one day after (Day 1). Nonparametric statistical analyses revealed significant time effects for several blood markers; however, no group differences were observed at any time point. In contrast, subjective scores of muscle soreness at several sites and systemic fatigue did not differ between groups at Post but were significantly lower in the MA group than in the Pla group on Day 1 (p<0.017). These findings suggest that although MA supplementation during a full marathon does not attenuate immediate post-race physiological or subjective responses, it may facilitate the recovery process by reducing perceived muscle soreness and fatigue the following day.

Genistein is one of the most estrogenic soy isoflavones. This study investigated the effects of genistein and 17β-estradiol (E2) on early chondrogenesis and extracellular matrix (ECM) production in chondrogenic ATDC5 cells. At low concentrations, E2, but not genistein, enhanced chondrogenic differentiation. Higher concentrations of E2 and genistein suppressed ECM production and expression of genes involved in chondroitin sulfate (CS) proteoglycan synthesis, including aggrecan core protein, CS synthases, 3′-phosphoadenosine 5′-phosphosulfate (PAPS) synthases, PAPS transporters, and CS sulfotransferases. Genistein exerted a stronger inhibitory effect than E2 and completely abolished the increase in Tgfb1 gene expression during chondrogenic differentiation. Treatment with estrogen receptor antagonist ICI 182780 did not inhibit E2- or genistein-dependent inhibition of chondrogenesis. Furthermore, E2 and genistein exhibited equivalent partial inhibition of transforming growth factor beta (TGF-β)-induced upregulation of Acan and Col2a1 expression. These results indicate that the inhibitory effects of high concentrations of E2 and genistein are dependent on TGF-β, but not the estrogen receptor pathway.

In this study, the effect of calcium alginate (Ca-Alg) on postprandial serum triglycerides (TG) was examined in healthy adults in a placebo-controlled, randomized, double-blind, crossover study. Eight healthy adults were given a fat-loaded food followed by placebo or 1.5 g (300 mg/capsule×5) of Ca-Alg, and serum TG and remnant-like lipoprotein cholesterol (RLP-C) levels were measured before and at various times (2, 3, 4 and 6 h) after consumption of the fat-loaded food. The results showed that TG and RLP-C levels were significantly lower at all time points in the Ca-Alg intake group compared to the control group, starting 2 h after consumption of the fat-loaded food. The area under the time curve (AUC_0-6h) and the highest level observed (C_max) up to 6 h after the food were also significantly lower in the Ca-Alg intake group than in the control group. Furthermore, biochemical analyses revealed that at 6 h after consumption of the fat-loaded food, ΔCa (change in serum calcium concentration) was significantly increased, whereas ΔNa (change in serum sodium concentration) was significantly decreased in the Ca-Alg intake group compared to the control group. These results indicate that Ca-Alg may have broad applications as a supplement that also contributes to the prevention of lifestyle-related diseases such as hyperlipidemia.

Alcoholic liver disease (ALD) is a significant health issue globally, arising as a consequence of excessive alcohol consumption. Currently, there is no specific pharmacotherapy for ALD, and the most effective treatment options remain abstinence or reduced alcohol intake. The Lieber-DeCarli liquid diet (LDC) has long been used to model ALD and other alcohol-related disorders in rodents. However, challenges in managing LDC, such as difficulties with food intake measurement and maintaining nutritional balance, complicate its use. To overcome these limitations, we developed a novel protocol by converting the liquid LDC into a solid form using agar, creating the solidified LDC diet (SLD). This adaptation facilitates precise control of food intake for pair-feeding and prevents nutritional deficiencies. Mice can be fed SLD either with or without 5% (w/w) ethanol over several weeks, and the addition of an oral ethanol gavage on the final day induces fatty liver and liver injury, mirroring the characteristics of ALD. This approach offers several advantages over traditional LDC, including streamlined diet preparation, consistent intake, and improved control over pair-feeding, reducing the variability of ethanol effects across subjects. The new SLD protocol promotes a more reliable modeling of ALD, contributing to more reproducible results and aiding research into pharmacological interventions for ALD and alcohol-related disorders.

It has been confirmed that Lacticaseibacillus paracasei (formerly designated as Lactobacillus paracasei: L. paracasei) K71, a lactic acid bacterium isolated from sakekasu (sake lees) has immunomodulatory and anti-obesity effects. This study aimed to investigate the effect of heat-killed L. paracasei K71 intake on reducing abdominal fat in a randomized, double-blind, placebo-controlled, parallel-group comparative trial. Eighty healthy male and female subjects with a BMI of ≥23 and <30 were selected and randomly assigned to one of two groups, a test food group and a placebo group. Subjects ingested either a test food containing 50 mg (approximately 1×10¹¹ bacteria) of heat-killed L. paracasei K71 or a placebo for 12 wk. Abdominal fat area and volume, as calculated by computed tomography, body weight, BMI, body fat percentage, waist circumference, hip circumference, waist-to-hip ratio, and blood markers were evaluated. In PPS, no significant between-group differences were observed in any item. On the other hand, in subjects with no significant changes in lifestyle, compared with the placebo group, the test food group showed significant decreases in subcutaneous fat area, visceral fat volume, subcutaneous fat volume, body fat percentage, and hip circumference after 12 wk. Moreover, no adverse events due to the test food containing heat-killed L. paracasei K71 were observed during the test period. These results suggest that continuous intake of heat-killed L. paracasei K71 has the effect of reducing abdominal fat in healthy subjects with a high BMI. This trial was registered at UMIN-CTR (UMIN000051324).

Natural disasters have occurred frequently in Japan and are currently the focus of much attention. The objective of this study is to investigate the association between the degree of health and food stockpiling for disasters across Japan. This study conducted an online survey from November 25 to 29, 2022, via a self-administered web-based questionnaire. The sample for this study consisted of 2,000 individuals over the age of 20 who registered with an online survey company. The associations between the degree of health and food stockpiling for disasters were analyzed (n=1,634). Only 11.9% of the participants had a high level of health, whereas 52.5% had a low level. Fewer than half of the participants had a middle level of health (35.6%). A multivariable logistic regression analysis was conducted to examine the association between the degree of health and food stockpiling for disasters. The analysis revealed a significant positive association between the degree of health and food stockpiling behavior for disasters. The levels of health, physical health and social health were significantly positively related to food stockpiling. Therefore, it is crucial to focus on personality traits to promote food stockpiling for disasters. This study emphasized that the degree of health should receive more attention in research, which could help promote food stockpiling for disasters.