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Although health screening plays a key role in the management of chronic diseases associated with lifestyle choices, brain health is not generally monitored, remaining a black box prior to the manifestation of clinical symptoms. Japan is unique in this regard, as brain MRI scans have been widely performed for more than two decades as part of Brain Dock, a comprehensive health screening programme. A vast number of stored images (well over a million) of longitudinal scans and extensive health data are available, offering a valuable resource for investigating the prevalence of various types of brain-related health conditions occurring throughout adulthood. In this paper, we report on the findings of our preliminary quantitative analysis of T1-weighted MRIs of the brain obtained from 13 980 subjects from three participating sites during the period 2015–19. We applied automated segmentation analysis and observed age-dependent volume loss of various brain structures. We subsequently investigated the effects of scan protocols and the feasibility of calibration for pooling the data. Last, the degree of brain atrophy was correlated with four known risk factors of dementia; blood glucose level, hypertension, obesity, and alcohol consumption. In this initial analysis, we identified brain ventricular volume as an effective marker of age-dependent brain atrophy, being highly sensitive to ageing and evidencing strong robustness against protocol variability. We established the normal range of ventricular volumes at each age, which is an essential first step for establishing criteria used to interpret data obtained for individual participants. We identified a subgroup of individuals at midlife with ventricles that substantially exceeded the average size. The correlation studies revealed that all four risk factors were associated with greater ventricular volumes at midlife, some of which reached highly significant sizes. This study demonstrates the feasibility of conducting a large-scale quantitative analysis of existing Brain Dock data in Japan. It will importantly guide future efforts to investigate the prevalence of large ventricles at midlife and the potential reduction of this prevalence, and hence of dementia risk, through lifestyle changes.

Tumor response and disease progression are assessed using imaging technologies. However, these technologies fail to detect tumor responses at the molecular level and clonal evolution. A potential surrogate for such parameters is using circulating tumor DNA (ctDNA). This study aimed to examine the quantity and composition of the ctDNA results of 29 cancer patients before and after dendritic cell (DC) immunotherapy and develop criteria to evaluate the molecular response to treatment based on these results. We categorized the patients into four categories based on percent changes in the total ctDNA compared with the baseline ctDNA titers, and this response assessment was termed genomic response evaluation criteria in solid tumors or gRECIST. Even those who are clinically evaluated as having a good response might harbor unfavorable tumor responses at the molecular level. Newly formed ctDNA levels can be the most prognostic parameter in tumor progression or the treatment response, while ctDNA clearance and the decline or rise in existing ctDNA did not change significantly in genomic response categories (gRECIST). More research is needed to support the clinical use of ctDNA in precision oncology and personalized cancer treatment.

Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using neoantigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for neoantigen-based immunotherapy and the importance of tailoring neoantigen-based immunotherapy in accordance with the liquid biopsy result in each treatment stage.

Introduction: Equol, an isoflavone derivative whose chemical structure is similar to estrogen, is considered as a potentially effective agent for relieving climacteric symptoms, for the prevention of the lifestyle-related diseases, and for aging care in post-menopausal women. We investigated the effect of an equol-containing supplement on metabolism and aging, and climacteric symptoms, with respect to internally-produced equol in post-menopausal women.Methods: A single center, randomized controlled trial (registration number: UMIN000030975) on 57 post-menopausal Japanese women (mean age: 56±5.37 years), was conducted. Twenty-seven women received the equol supplement, while the remaining received Control. Metabolic and aging-related biomarkers were compared before and after the 3-month intervention. Climacteric symptoms were assessed every month using a validated self-administered questionnaire in Japanese post-menopausal women. Results: Three months post intervention, the treatment group showed significant improvement in climacteric symptoms, when compared to the Control group (81% vs. 53% respectively, p=0.045). We did not observe any beneficial effect on metabolic and aging-related biomarkers in the intervention group. However, in certain populations significant improvement in skin auto-fluorescence, which is a measurement of AGE skin products, and visceral fat area was observed, especially among equol producers. Conclusion: Women receiving equol supplement showed improved climacteric symptoms. This study offered a new hypothesis that there may be a synergy between supplemented equol and endogenously-produced equol to improve skin aging and visceral fat in certain populations.

Objective: We investigated the effect of an equol-containing supplement on metabolism and aging, and climacteric symptoms, with respect to internally-produced equol. Methods: A single center, randomized controlled trial (registration number: UMIN000030975) on 57 post-menopausal Japanese women (mean age: 56±5.37 years), was conducted. Twenty-seven women received the equol supplement, while the remaining received placebo. Metabolic and aging-related biomarkers were compared before and after the 3-month intervention. Climacteric symptoms were assessed every month using a validated self-administered questionnaire in Japanese post-menopausal women. Results: Three months post intervention, the treatment group showed significant improvement in climacteric symptoms, when compared to the placebo group (81% vs. 53% respectively, p=0.045). We did not observe any beneficial effect on metabolic and aging-related biomarkers in the intervention group. However, in certain populations significant improvement in skin auto-fluorescence, which is a measurement of AGE skin products, and visceral fat area was observed, especially among equol producers. Conclusion: Women receiving equol supplement showed improved climacteric symptoms. This study offered a new hypothesis that there may be a synergy between supplemented equol and endogenously-produced equol to improve skin aging and visceral fat in certain populations.

Objective: To examine changes in the bone and cardiovascular parameters and tolerability in middle-aged Japanese women taking equol supplement for a year. Design: This was a prospective observational study. Subjects and Setting: Participants were 74 women receiving outpatient care at Hamasite Medical Clinic, Minato-ku, Tokyo, from 2013 to 2015. Interventions: Participants received per oral equol-containing supplement, 10 mg/day. Outcome measures: The primary outcome measures were percent changes in bone and cardiovascular parameters after 1 year supplementation with equol. The secondary measures included factors affecting the parameter changes and adverse effects associated with equol use for a year. Results: Reduction in arterial stiffness was observed after 12 months of equol supplement (1402.3 cm/s vs.1367.3 cm/s, p

Introduction Equol, an isoflavone derivative whose chemical structure is similar to estrogen, is considered a potentially effective agent for relieving climacteric symptoms, for the prevention of lifestyle-related diseases, and for aging care in postmenopausal women. We investigated the effect of an equol-containing supplement on metabolism and aging and climacteric symptoms with respect to internally produced equol in postmenopausal women. Methods A single-center, randomized controlled trial (registration number: UMIN000030975) on 57 postmenopausal Japanese women (mean age: 56±5.37 years) was conducted. Twenty-seven women received the equol supplement, while the remaining received control. Metabolic and aging-related biomarkers were compared before and after the 3-month intervention. Climacteric symptoms were assessed every month using a validated self-administered questionnaire in Japanese postmenopausal women. Results Three months post-intervention, the treatment group showed significant improvement in climacteric symptoms compared to the control group (81% vs. 53%, respectively, p = 0.045). We did not observe any beneficial effect on metabolic and aging-related biomarkers in the intervention group. However, in certain populations, significant improvement in skin autofluorescence, which is a measurement of AGE skin products, and visceral fat area was observed, especially among equol producers. Conclusion Women receiving equol supplementation showed improved climacteric symptoms. This study offered a new hypothesis that there may be a synergy between supplemented equol and endogenously produced equol to improve skin aging and visceral fat in certain populations.

Equol, an active metabolite possessing estrogen-like activity, is produced by the action of intestinal flora on soy isoflavones. There is an increasing evidence regarding its efficacy in the relief of menopausal symptoms, suppression of decreased bone mineral density, and lipid profile improvement. Only those with equol-producing capacity, however, seem to benefit. Thus, we examined the relationship between equol producer status and parameters associated with lifestyle-related diseases in women from their 20s to 80s.This cross-sectional study was conducted among 743 women (21-89 y; average age: 52.5 ± 11.8 y) who have undergone health screening at Tokyo Midtown Medical Center and given consent to participate in the study. The relationship between equol producer status and metabolic parameters was assessed.In our study, 236 women (32%) were equol producers. Equol producers had significantly lower triglycerides and higher high-density lipoprotein cholesterol levels compared with nonproducers. Equol-producing women in their 50s showed significantly lower body fat level, visceral fat area, triglyceride levels, pulse wave velocity, uric acid levels, and high sensitivity C-reactive protein levels. In addition, women in their 60s showed significantly higher levels of high-density lipoprotein cholesterol. In multivariate logistic regression, for women in their 50s, equol production was significantly associated with lower arterial stiffness and uric acid levels, and a high ratio of eicosapentaenoic acid to arachidonic acid, whereas it was significantly associated with lower urinary N-telopeptides in their 60s.Equol producer status was associated with favorable metabolic parameters, in women in the early phase postmenopause, with the transitional periods noted with declining intrinsic estrogen levels.

Objective Equol is an active metabolite of isoflavones produced by gut microbiota. It is beneficial to health; however, equol-producing ability varies greatly among individuals. These variations depend on the host's gut microbiota and lifestyle habits including diet. We investigated the relationship between the gut microbiota, lifestyle habits including diet, and equol-producing ability in postmenopausal Japanese women. Methods We studied 58 postmenopausal Japanese women aged 48 to 69 years who visited the Sendai Medical Center in January, 2018. Self-administered questionnaires assessed their recent and remote food intake histories and lifestyle habits. Fecal microbiome analysis was performed using a next-generation sequencer. Urinary equol was measured using an immunochromatographic strip test. Women with urinary equol concentration >1.0 μM were defined as equol producers. Results Equol-producing bacteria were identified in 97% (56) of women; however, only 13 (22%) were equol producers. Equol producers showed significantly higher microflora diversity (P = 0.002), and significantly different recent and remote food intake patterns compared with equol nonproducers. Higher consumption of foods such as meat, fish, soy, vegetables, and Japanese snacks positively affected microbial diversity and equol production, whereas a high intake of Ramen and smoking showed negative effects. Conclusion Equol production might not depend on the quantity, but on the quality of equol-producing bacteria. High microbial diversity might enhance equol production. Increasing microbial diversity through healthy lifestyle habits and habitual consumption of a wide variety of foods might be useful to maintain a healthy gut environment for equol production.