BACKGROUND: Among the more than 300 mycotoxins that are known to have toxic effects on animals and humans, Fusarium toxins deoxynivalenol (DON), T-2 and HT-2 toxins (T2/HT2), and zearalenone (ZEN) are frequently detected in domestic agricultural products. This study aimed to assess DON, T2/HT2, and ZEN exposure in Japanese adults by measuring urinary mycotoxins, observing their distributions, and making comparisons with data from other countries. METHODS: A total of 201 individuals participated in the study. Twenty-four-hour urine samples were collected from young adults (34 men and 35 women) in the Tokai region (urban area) and spot urine samples were collected from middle-aged and elderly adults (64 men and 68 women) in the Donan area of Hokkaido Prefecture (rural area). Urinary DON, T2/HT2, and ZEN levels were measured using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: For DON, T2/HT2, and ZEN, the detection frequencies above the limit of detection (LOD) level (0.15, 0.13, and 0.01 µg/L, respectively) in all the samples were 53%, 26%, and 71%, respectively. The median concentrations (95^th percentile) of urinary DON, HT2, and ZEN were 0.19 (3.93), CONCLUSIONS This study represents the first comprehensive exposure assessment for DON, T2/HT2, and ZEN in Japanese adults using human biomonitoring methods. These data provide valuable information for a better understanding of mycotoxin exposure in Japan.
Humans ; Zearalenone/urine* ; Japan ; Male ; Female ; Trichothecenes/urine* ; T-2 Toxin/urine* ; Biological Monitoring ; Adult ; Middle Aged ; Aged ; Cross-Sectional Studies ; Young Adult ; Mycotoxins/urine* ; Environmental Exposure/analysis* ; East Asian People

BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

BACKGROUND: Although serum carotene may contribute to dementia prevention, there is a lack of longitudinal evidence for early cognitive decline before dementia symptoms. The aim of this study was to examine whether serum carotene levels were associated with annually evaluated cognitive trajectories among the Japanese general population. METHODS: Among 581 baseline participants, 199 individuals (83 males; mean age [min, max], 62.7 [39, 90] years) who underwent cognitive assessments more than twice after baseline were analyzed. "Attention" levels were assessed using one- and three-target Digit Cancellation Tests (D-CAT1 and D-CAT3). "General cognitive ability" was assessed by the short version of Mini-Mental State Examination (SMMSE). Serum carotenes (α-carotene, β-carotene and lycopene) were measured by high-performance liquid chromatography. After the measurements, we calculated total carotene levels by summing up the levels of all measured carotene. Carotene levels were categorized into three groups for analysis (low: 0%-25%, middle: 25%-75%, and high: 75%-100%). A linear mixed model was used to estimate the slope of the D-CAT score trajectory and to compare it between three categories. RESULTS: Compared with the middle carotene group, decline of attention was faster in the D-CAT1 for low β-carotene (β = -3.48, p = 0.035), lycopene (β = -3.10, p = 0.062), and total carotene (β = -4.75, p = 0.003), but not for α-carotene (β = -2.60, p = 0.111). For the D-CAT3, decline of attention was faster in the group of low lycopene (β = -3.17, p = 0.002) and total carotene (β = -2.17, p = 0.037) compared with the middle carotene group, while no clear association for α-carotene (β = -0.67, p = 0.521) and β-carotene (β = -0.64, p = 0.639). There were no clear associations between serum carotene and the SMMSE score. CONCLUSIONS These findings suggest low levels of serum lycopene are associated with a decline of attention in the setting of the general population.
Humans ; Male ; Carotenoids/blood* ; Female ; Longitudinal Studies ; Middle Aged ; Japan ; Aged ; Adult ; Aged, 80 and over ; Attention ; Lycopene ; East Asian People

BACKGROUND: Difficulty in chewing has been shown to be associated with increased mortality, geriatric syndromes, and poor activities of daily living, indicating the need for intervention. Chewing difficulties are related to tooth loss, periodontitis, dry mouth, and a number of oral health conditions. Diabetes mellitus (DM) is one of the major causes of global burden of diseases, and has been associated with poor oral health. Prospective association between oral health status and the development of diabetes has also been reported. However, relationship between glycemic control and self-reported chewing difficulty remains less explored in working-age populations. The objective of this study is to cross-sectionally explore the association between fasting blood glucose (FBG) and self-reported chewing difficulty in adults working in a Japanese worksite. METHODS: Participants from the Aichi Workers' Cohort Study who responded to the 2018 survey were included. Participants were categorized into five FBG groups (<100, 100-109, 110-125, 126-159, and ≥160 mg/dl). Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for chewing difficulty were estimated using logistic regression adjusted for age, sex, body mass index, smoking and alcohol consumption status, number of teeth, presence of periodontal disease and the number of anti-diabetic medication classes. RESULTS: A total of 164 participants (4.2%) reported difficulty with chewing, the prevalence of which tended to increase with increasing FBG level. FBG ≥160 mg/dl was significantly and strongly associated with difficulty with chewing in the final multivariable model (multivariable OR 3.84 [95% CI 1.13-13.0]). CONCLUSIONS A relationship between higher FBG levels and difficulty with chewing was observed, independent of potential confounding factors. However, prospective or interventional studies are needed to determine causality.
Humans ; Male ; Japan/epidemiology* ; Female ; Mastication/physiology* ; Middle Aged ; Adult ; Blood Glucose/analysis* ; Cross-Sectional Studies ; Fasting/blood* ; Cohort Studies ; Oral Health ; Prevalence

The human gut microbiota changes under the influence of environmental and genetic factors, affecting human health. Extensive studies have revealed that the gut microbiome is closely associated with many non-intestinal diseases. Among these, the influence of the gut microbiome on cancer biology and the efficacy of cancer therapy has attracted much attention. Prostate cancer cells are affected by direct contact with the microbiota of local tissues and urine, and a relationship between prostate cancer cells and the gut microbiota has been suggested. In the human gut microbiota, bacterial composition differs depending on prostate cancer characteristics, such as histological grade and castration resistance. Moreover, the involvement of several intestinal bacteria in testosterone metabolism has been demonstrated, suggesting that they may affect prostate cancer progression and treatment through this mechanism. Basic research indicates that the gut microbiome also plays an important role in the underlying biology of prostate cancer through multiple mechanisms owing to the activity of microbial-derived metabolites and components. In this review, we describe the evidence surrounding the emerging relationship between the gut microbiome and prostate cancer, termed the “gut-prostate axis.”