Effects of polymethoxyflavonoids on T helper 17 cell differentiation in vitro and in vivo.

The Journal of Medical Investigation : JMI


Essential Oil of Citrus sudachi Suppresses T Cell Activation Both In Vitro and In Vivo.

Journal of Nutritional Science and Vitaminology


Validity of dietary diversity assessed using short-form questionnaire among older Japanese community dwellers.

The validity of dietary variety score (DVS) using a short-form questionnaire has not been investigated using dietary diversity based on a quantitative distribution of consumed foods in older Japanese. We examined the association between DVS and objective dietary diversity using a Quantitative Index for Dietary Diversity (QUANTIDD) based on the quantitative distribution of foods consumed by older Japanese community dwellers. The subjects were 65 older Japanese community dwellers aged 60?79 years. We used two kinds of scores for assessment of dietary diversity. At first, dietary diversity was determined using DVS calculated from answers to a questionnaire about frequencies of intake of 10 food groups. Second, dietary intake was assessed using a 3-day dietary record with photographs, and dietary diversity was determined using QUANTIDD. The relationships between DVS and QUANTIDD were assessed using partial correlation coefficients controlling for confounders. The correlation coefficient between DVS and QUANTIDD was moderate (r=0.212-0.458). After controlling for confounders, those correlation coefficient between DVS and QUANTIDD remained moderate. The findings suggest that there was a moderate relationship between DVS and QUANTIDD, and DVS using a short-form questionnaire may be useful for assessing dietary diversity in older Japanese community dwellers. J. Med. Invest. 69 : 31-37, February, 2022.


Dietary diversity and food choice motives during the COVID-19 pandemic among older Japanese: An Internet Panel Survey.

The findings suggest that the COVID-19 pandemic was associated with an increase in some food choice motives and a decrease in the frequency of eating out among elderly female Japanese.

Asia Pacific Journal of Clinical Nutrition


Nobiletin suppresses the development of experimental autoimmune encephalomyelitis mediated by modulation of T helper 17 cell differentiation

Multiple sclerosis is an organ-specific autoimmune disease that targets the myelin antigen in the central nervous system. Nobiletin is a dietary polymethoxylated flavonoid found in citrus fruits. In this study, we investigated how nobiletin affects the disease state and immune responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis mice. Nobiletin was administered orally from 14 days before immunization until the end of the experiment, and clinical scores were determined. The production levels of interleukin-17A and interferon-γ were measured in a culture supernatant of splenocytes stimulated with myelin oligodendrocyte glycoprotein. In addition, flow cytometric analysis was performed to examine the effect of nobiletin on T cell differentiation . Admin-istration of nobiletin significantly decreased the clinical score and interleukin-17A production in splenocytes. Furthermore, analysis showed that nobiletin significantly suppressed Th17 cell differentiation and interleukin-17A production in a dose-dependent manner. The results suggest that nobiletin attenuates experimental autoimmune encephalomyelitis severity through modulation of Th17 cell differentiation.

Journal of Clinical Biochemistry and Nutrition


Intake of isoflavones reduces the risk of all-cause mortality in middle-aged Japanese.

The findings suggest that a higher intake of isoflavones might decrease the risk of all-cause mortality, especially in middle-aged Japanese.

There were 491 deaths during the follow-up period. We found inverse associations of the intake of total soy products and intake of each of the isoflavones with all-cause mortality (p for trend < 0.05) in subjects aged < 60 years: the multivariate-adjusted hazard ratios (95% confidence intervals) for all-cause mortality in the highest intake group (third tertile) of total soy products and total isoflavones were 0.32 (0.13-0.78) and 0.35 (0.17-0.73), respectively, compared with the reference group (first tertile). In contrast, there were no significant associations of intake amounts of legumes, soybeans, and isoflavones with all-cause mortality in subjects aged 60 years or older.


Citrus Polymethoxyflavonoids, Nobiletin, Heptamethoxyflavone and Natsudaidain, Suppress T Cell Activation In Vitro and In Vivo


Analysis of cereal extracts as conditioning solutes to suppress the initial attachment of Escherichia coli to abiotic surfaces


Dietary diversity and characteristics of lifestyle and awareness of health in Japanese workers:a cross-sectional study.

The aim of this study was to clarify the characteristics of lifestyle and health awareness according to dietary diversity in a Japanese worksite population. The participants were 1,312 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The characteristics of lifestyle and health awareness according to quartiles of the QUANTIDD score were assessed using the chi-square test and a general linear model. The higher the QUANTIDD score was, the larger were the proportions of participants who knew the appropriate amount of dietary intake and participants who referred to nutritional component information when choosing and/or buying food. Among participants with higher QUANTIDD scores, the proportion of participants who considered their current diet was good was high in women, whereas the proportion of participants who wanted to improve their diet in the future was high in men. Those results indicate that higher dietary diversity was related to better characteristics of lifestyle and awareness of health. J. Med. Invest. 67 : 255-264, August, 2020.

The aim of this study was to clarify the characteristics of lifestyle and health awareness according to dietary diversity in a Japanese worksite population. The participants were 1,312 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The characteristics of lifestyle and health awareness according to quartiles of the QUANTIDD score were assessed using the chi-square test and a general linear model. The higher the QUANTIDD score was, the larger were the proportions of participants who knew the appropriate amount of dietary intake and participants who referred to nutritional component information when choosing and / or buying food. Among participants with higher QUANTIDD scores, the proportion of participants who considered their current diet was good was high in women, whereas the proportion of participants who wanted to improve their diet in the future was high in men. Those results indicate that higher dietary diversity was related to better characteristics of lifestyle and awareness of health. J. Med. Invest. 67 : 255-264, August, 2020.

The Journal of Medical Investigation : JMI


Sudachitin, polymethoxyflavone from Citrus sudachi, enhances antigen-specific cellular and humoral immune responses in BALB/c mice.


Associations of dietary diversity with allergic diseases in Japanese workers: a cross-sectional study.

The aim of this study was to determine the associations of dietary diversity with prevalences of allergic diseases. The participants were 1,317 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics and current medical histories of allergic diseases using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The ORs and 95% CIs for each of the allergic diseases with a 1 standard deviation (SD) increase in the QUANTIDD score were estimated, controlling for age, family history of allergic diseases, education, smoking, drinking, physical activity, energy intake and BMI. Higher dietary diversity showed significant inverse dose-response relationships with allergic diseases and allergic rhinitis in women. Multivariate-adjusted ORs (95% CI) for allergic diseases and allergic rhinitis with 1 SD increase in the QUANTIDD score were 0.77 (95% CI: 0.60-0.98, p=0.037) and 0.69 (95% CI: 0.53-0.90, p=0.007), respectively, in women. There were no significant associations between dietary diversity and allergic diseases in men. The results indicate that there is an inverse association between higher dietary diversity and allergic rhinitis in Japanese female workers.


Associations of marital and parental status and family members living together with health-related behaviors in Japanese young workers : a cross-sectional study.

The aim of this study was to clarify the associations of family members living together with healthrelated behaviors in Japanese young workers. The participants were 300 men and women aged 20-39 years in 2015 who had a job. A web-based self-administered questionnaire on status of partnering and parenting, number of family members living together, dietary habits, drinking habit, smoking habit, self-rated health, employment status, working time and commuting time was conducted through Internet. Multiple logistic regression analysis and general linear models were used to assess the association of family members living together with healthrelated behaviors. The multivariate-adjusted odds ratio (95% confidence interval, p-value) for current drinking in unmarried participants living with their parents compared to unmarried participants living alone was 0.35 (0.13-0.93, p=0.036). The adjusted means of frequency of breakfast skipping and frequency of eating out showed a trend for inverse associations with the presence of a partner and children. However, those associations disappeared after adjustment for age of youngest child. The findings suggest that the presence of parents might affect drinking behavior and that age of youngest child living together might affect the frequency of breakfast skipping in young Japanese workers. J. Med. Invest. 66 : 141-147, February, 2019.


Nobiletin Enhances Induction of Antigen-Specific Immune Responses in BALB/c Mice Immunized with Ovalbumin.

Journal of Nutritional Science and Vitaminology


Soy food and isoflavone intake reduces the risk of cognitive impairment in elderly Japanese women.

Data were derived from the National Institute for Longevity Sciences-Longitudinal Study of Aging. Subjects comprised 403 men and 373 women aged 60-81 years at baseline who participated in the follow-up study at least once. Bean, soy product and soy isoflavone intake was assessed using a 3-day dietary record at baseline. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). MMSE scores of 23 were used to define cognitive impairment. The relationship between bean, soy product and soy isoflavone intake and cognitive impairment was assessed using a generalized estimating equation. Multivariate-adjusted odds ratios (95% confidence intervals) for cognitive impairment with a 1 s.d. increase in total bean, total soybean and total soy isoflavone intakes were 0.48 (0.28-0.81; p = 0.006), 0.51 (0.32-0.83; p = 0.007), and 0.55 (0.32-0.93; p = 0.026), respectively, in women. Total soybean and soy isoflavone intake might decrease the risk of cognitive impairment in elderly Japanese women.


Soy product and isoflavone intake associations with allergic diseases in Japanese workers: rhinitis, dermatitis and asthma.

The aim of this study was to determine the associations of intake of soy products and isoflavones with allergic diseases. We conducted a cross-sectional study in 1437 participants (aged 20-64 years) who were living in Tokushima Prefecture, Japan during the period 2010- 2011. We obtained anthropometric data and information on life style characteristics including dietary intake and current medical histories of allergic diseases using a structural self-administered questionnaire. Multiple logistic regression models were used to assess the associations of soy products and isoflavones with allergic diseases after controlling for age, family history of allergic diseases, smoking, drinking, physical activity, energy intake, BMI and dietary factors. Intake of soy products showed significant inverse dose-response relationships with allergic rhinitis. The third quartile for soy products had an adjusted OR of 0.56 (95% CI: 0.35-0.91) compared to the reference group (first quartile), though intake of soy products showed no dose-response relationship with atopic dermatitis. Intake of soy isoflavones showed a significant inverse dose-response relationship with atopic dermatitis, though the association between intake of soy isoflavones and atopic dermatitis was U-shaped after adjustments for potential confounders. On the other hand, the associations between intake of soy isoflavones and other allergic diseases were not significant. The results indicate that higher intake of soy products is associated with reduced risk of allergic rhinitis in Japanese workers. Furthermore, moderate intake amounts of soy products and soy isoflavones are associated with inverse risk of atopic dermatitis.

Asia Pacific Journal of Clinical Nutrition


Associations between intake of dietary fermented soy food and concentrations of inflammatory markers: a cross-sectional study in Japanese workers

Epidemiological investigations have shown that consumption of soybeans or soy foods reduces the risk of the development of cardiovascular disease, cancer and osteoporosis. The aim of this study was to determine the associations between different soy foods and inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and IL-18, in Japanese workers. The cross-sectional study included 1,426 Japanese workers (1,053 men and 373 women) aged 20 to 64 years. Intake of 12 soy foods was estimated by a validated food frequency questionnaire. Associations of total soy foods, fermented soy food, non-fermented soy food, soy isoflavone with hs-CRP, IL-6, and IL-18 levels were examined by general linear model regression analysis. We found that total fermented soy food intake was inversely associated with multivariable-adjusted geometric concentration of IL-6 in men (Q1:1.03 pg/mL, Q5:0.94 pg /mL;P for trend = 0.031). Furthermore, it was shown that IL-6 concentrations were inversely associated with miso intake (β = -0.068;p = 0.034) and soy sauce intake in men (β = -0.074;p = 0.018). This study suggests that intake of total fermented soy food, miso and soy sauce be associated with IL-6 concentrations in Japanese men. J. Med. Invest. 65:74-80, February, 2018.


Brazilian Green Propolis Promotes Weight Loss and Reduces Fat Accumulation in C57BL/6 Mice Fed A High-Fat Diet

Propolis is a bee product with various biological properties. C57BL/6 mice were fed a high-fat diet and treated with propolis for 14 weeks. Body weight in mice treated with 2% propolis was less than that in control mice from 3 weeks after the start of treatment until 14 weeks except for the 7th week. Mice treated with propolis showed significantly lower epididymal fat weight and subcutaneous fat weight. Infiltration of epididymal fat by macrophages and T cells was reduced in the propolis group. Supplementation of propolis increased feces weight and fat content in feces, suggesting that mechanisms of weight reduction by propolis partly include a laxative effect and inhibition of fat absorption.


Extracts of citrus Sudachi peel attenuate body weight gain in C57BL/6 mice fed a high-fat diet

Citrus Sudachi is the special local product of Tokushima Prefecture, and over 98% of Sudachi consumed in Japan every year is produced in Tokushima Prefecture. In this study, we evaluated the function of sudachi peel extract (SPE) using an animal model of obesity. C57BL/6 mice were fed a high-fat diet containing 1% SPE powder. Treatment with SPE significantly decreased body weight compared to that of mice fed a high-fat diet. A significant difference in body weight was observed between the control and SPE groups from 7 weeks after the start of the experiment, the significant difference continued until the end of the 14-week experiment. Reduction of blood glucose levels following insulin administration in SPE-treated mice was grater than that in control mice. Determination of mRNA expression in adipose tissue showed that the expression level of TNF-α in the SPE group was significantly decreased compared to that on the control group. These results suggest that SPE potentially has the ability to attenuate body weight gain. J. Med. Invest. 64: 20-23, February, 2017.

The Journal of Medical Investigation : JMI


Effects of chemotherapy on gene expression of lingual taste receptors in patients with head and neck cancer.

We aimed to test the hypothesis that chemotherapy changes the gene expression of taste receptors in the tongue to induce dysgeusia in patients with head and neck cancer. Prospective observation study. We enrolled 21 patients who received chemoradiotherapy and five patients who underwent radiotherapy for head and neck cancer. The messenger RNA (mRNA) levels of the taste receptor subunits T1R1, T1R2, T1R3, and T2R5 were measured in lingual mucosa scrapings obtained with a small spatula. The perception thresholds of umami, sweet, and bitter tastes were assessed by the whole mouth gustatory test. In four patients with severe stomatitis induced by chemoradiotherapy, the mRNA levels of T1R1, T1R2, T1R3, and T2R5 in the lingual mucosa were significantly decreased. However, in 17 patients with mild/moderate stomatitis, the mRNA levels of T1R3 were significantly and transiently decreased, whereas those of T1R1 and T1R2 remained unchanged and those of T2R5 mRNA were significantly and transiently increased after chemotherapy. There was a significant negative correlation between the perception thresholds of umami or sweet tastes and lingual mRNA levels of T1R3 in patients with mild/moderate stomatitis after chemotherapy. Although the perception threshold of bitter taste remained unchanged, lingual mRNA levels of T2R5 were significantly increased in patients who complained of phantogeusia after chemotherapy. Chemotherapy specifically changed the gene expression of T1R3 and T2R5 in head and neck cancer patients with mild/moderate stomatitis, resulting in both dysgeusia of umami and sweet tastes as well as phantogeusia. 4. Laryngoscope, 126:E103-E109, 2016.


Dietary ribonucleic Acid suppresses inflammation of adipose tissue and improves glucose intolerance that is mediated by immune cells in C57BL/6 mice fed a high-fat diet.

Recent evidence suggests that immune cells play an important role in differentiation of inflammatory macrophages in adipose tissue, which contributes to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown to modulate immune function. We hypothesized that RNA affects immune cell function in adipose tissue and then improves inflammatory response in adipose tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk. An oral glucose tolerance test was performed. Supplementation of dietary RNA in C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC) after oral glucose administration than that for control mice. The mRNA expression levels of inflammation-related cytokines in adipose tissue and serum interleukin-6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG-1 knockout mice. These results indicate that RNA improves inflammation in adipose tissue and reduces the AUC value following oral glucose administration in a T and B cell-dependent manner.

Journal of Nutritional Science and Vitaminology


Vitamin A Deficiency Impairs Induction of Oral Tolerance in Mice.

Oral tolerance is a phenomenon of induction of systemic unresponsiveness to antigens ingested by the oral route and loss of immune response. Studies have shown the importance of vitamin A in oral tolerance in vitro but not in an in vivo experimental model. Therefore, we carried out experiments to determine how vitamin A deficiency affects tolerance induction and the ability of mesenteric lymph node (MLN) CD11c(+) cells to induce regulatory T cells (Tregs). Immunological tolerance was induced by oral ovalbumin (OVA) administration in vitamin A-sufficient mice. OVA-specific antibody and cytokine production were significantly reduced. On the other hand, in vitamin A-deficient mice, both OVA-specific antibody and cytokine production were not suppressed by oral OVA administration. Regarding induction of Tregs, the conversion rate of Foxp3(+) cells from naïve CD4(+) cell by CD11c(+) cells was decreased in vitamin A-deficient mice. Our study indicates that vitamin A deficiency causes the breakdown of oral tolerance in vivo.


Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle.

Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain. C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro. Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle. Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders.


Academic Degrees and Teacher Competency Requirements in Dietitian and National Registered Dietitian Training Facilities

管理栄養士・栄養士養成施設における教員の学位取得状況および教員に求められる知識や技能等に関する調査

Objective: To obtain personnel information of teaching staff in universities, colleges, and vocational schools with dietitian and/or registered dietitian programs, including number of teaching staff with a dietitian or registered dietitian license and the distribution of academic degrees. Competencies (e.g., education, research administration) required of staff for teaching the curriculum were also evaluated.Methods: A mail survey was conducted in February and March 2013 inquiring on number of teaching staff, number of teaching staff with a dietitian license or who were registered dietitians, and age and position of staff. In addition, staff competencies were evaluated for their importance in dietitian and registered dietitian training facilities.Results: The response rate was 66.1% (78 schools) and 68.5% (102 schools) for dietitian and registered dietitian training facilities, respectively. Most teachers were aged 30~49 in both dietitian and registered dietitian training facilities. In registered dietitian training facilities, 40% of teachers over age 30 had their Ph.D., and 39.5%, 75.9%, and 66.5% aged 20~29, 30~49, and 50~65 had a master's and/or doctoral degree, respectively. In dietitian training facilities, about 20% of teachers over age 30 had a Ph.D., and 28.4%, 47.4%, and 44.0% aged 20~29, 30~49, and 50~65 had a master's and/or doctoral degree, respectively. "Education" was considered the most important competency.Conclusion: We obtained basic information concerning age and education characteristics of teachers in dietitian and national registered dietitian training schools. Education was identified by facility directors as the most important competency.

【目的】管理栄養士および栄養士養成施設において管理栄養士・栄養士免許を有する教員の数，教員の学位取得状況，各養成施設において教員に求められる知識や技能等を明らかにする．【方法】教員の学位取得状況，教員に求められる知識や技能および担当科目等の基礎情報に関する質問用紙を作成し，2013年2∼3月に全国の管理栄養士および栄養士養成施設に郵送した．【結果】回答が得られた施設は，管理栄養士養成施設78校(回答率66.1%)，栄養士養成施設102校であった(回答率68.5%)．教員の年齢区分では管理栄養士および栄養士養成施設共に30∼49歳が最も高かった．管理栄養士養成施設で管理栄養士免許を有する教員で博士の学位を有する者の割合は年齢層が上昇するごとに増え30歳以上では約4割程度であった．管理栄養士養成施設において管理栄養士免許保有教員のうち修士または博士の学位を有するものは，20∼29歳42.5%，30∼49歳75.7%，50∼65歳66.5%であった．栄養士養成施設において管理栄養士免許を有する教員で博士の学位を有するものの割合は30歳以上で約2割程度であった．栄養士養成校において管理栄養士免許保有教員のうち修士および博士の学位を有するものは，20∼29歳28.4%，30∼49歳47.4%，50∼65歳42.0%であった．養成施設が教員に求める知識や技能に関しては，「教育」が最も高く，エフォートに対する割合としては50∼59%と回答する施設が最も多かった．【結論】管理栄養士および栄養士養成施設における管理栄養士または栄養士免許を有する教員の年齢構成，学位取得状況等の基本情報が得られた．また養成施設が教員に対して求める知識や技能として最も高いのは「教育」であった．

The Japanese Journal of Nutrition and Dietetics


Treatment with buckwheat bran extract prevents the elevation of serum triglyceride levels and fatty liver in KK-A(y) mice.

Buckwheat powder or protein has been shown to decrease the total serum cholesterol level in non-diabetic mice or rats. However, the lipid-lowering effect of buckwheat bran extract (BBE) in diabetic mice has not been fully elucidated. KK-A(y) mice that received six-week treatment with BBE showed decreased body weight and liver weight compared to those of control (vehicle) mice. However, there was no significant difference in food intake. BBE treatments prevented liver triglyceride accumulation and decreased the serum level of triglycerides. In addition, mRNA expression levels lipogenic enzyme genes, fatty acid synthase, acetyl-coenzyme a oxidase and stearyl-coenzyme a desaturase 1, but not those of -oxidized enzyme genes, were decreased in BBE-treated mice. Level of transcription factors ChREBP and SREBP1c, transcripts of lipogenic genes, were also decreased in BBE-treated mice. These results suggest that chronic treatment with BBE derivatives could have beneficial effects on hypertriglycemia in patients with type 2 diabetes mellitus.


Association between blood levels of PCDDs/PCDFs/dioxin-like PCBs and history of allergic and other diseases in the Japanese population.

Previous studies reported that exposure to dioxins was associated with an increased risk of various diseases in general populations. The aim of this study was to examine the association between levels of dioxins in blood and allergic and other diseases. We conducted a cross-sectional study on 1,063 men and 1,201 women (aged 15-76 years), who were living throughout Japan and not occupationally exposed to dioxins, during 2002-2010. In fasting blood samples, polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like PCBs (DL-PCBs) were analyzed by isotope dilution high-resolution gas chromatography/mass spectrometry. We obtained information on life style and self-reported history of diseases using a questionnaire. Blood pressure, blood levels of hemoglobin A1c, and serum lipids were also measured. Multiple logistic regression models were used to analyze the association between dioxin levels in blood and various diseases. Toxic equivalents of PCDDs/PCDFs and total dioxins showed significant inverse dose-response relationships with atopic dermatitis, after adjustments for potential confounders. The highest quartile for total dioxins had an adjusted odds ratio of 0.26 (95 % confidence interval 0.08-0.70) compared to the reference group (first quartile). The odds ratios for hypertension, diabetes mellitus, hyperlipidemia, gout in men, and gynecologic diseases in women significantly increased with increasing toxic equivalents of PCDDs/PCDFs, DL-PCBs, and total dioxins in blood. The present findings suggest that background exposure to dioxins was associated with reduced risk of atopic dermatitis. The results also support the idea that low-level exposure to dioxins is associated with an increased risk of diabetes, hypertension, and hyperlipidemia.

International Archives of Occupational and Environmental Health


Epidemiology : Relationship between Physical Activity and Metabolic Syndrome in Male Workers

勤労男性の生活における身体活動とメタボリックシンドロームとの関連

Journal of the The Japan Diabetes Society


Period between Dinner and Bedtime Is Related to Hypertension

勤労者の夕食終了から就寝時間までの間隔と健康状態との関係

The aim of this study was to examine the association between the period between dinner and bedtime, and various adult lifestyle-related diseases in the workplace. We analyzed 470 men and 252 women aged 20-65 years who had been enrolled in baseline surveys conducted for the Tokushima Diabetes Cohort Study in a workplace setting in Tokushima prefecture. Multiple logistic regression models were used for analyzing the association of the time between dinner and bedtime and the prevalence rates of adult lifestyle-related diseases. The period between dinner and bedtime tended to show an inverse dose-response relationship with hypertension (p for trend = 0.04) after adjustment for age, sex and other potential confounders. The group with the longest period between dinner and bedtime had an adjusted odds ratio of 0.38 (95% confidence interval 0.17-0.82) compared to the reference group (first quartile group) . Additionally, the period between dinner and bedtime showed an inverse dose-response relationship with hypertension for subjects who ate dinner after 21:00 (p for trend = 0.02) . These results indicate that the period between dinner and bedtime is inversely associated with the prevalence of hypertension.

近年, 生活習慣病や精神疾患などを抱える勤労者が増加している．一方, 朝食欠食, 過食, 身体活動の不足, 短時間睡眠など, 生活習慣の乱れが疾病の発症に関連することが報告されている．我々は, 徳島県勤労者において, 夕食終了から就寝までの間隔と生活習慣病の有病状況との関係について横断研究を行った．20歳以上の勤労者735名を対象に, 食物摂取頻度調査, 生活に関する質問票調査, 採血, 身体計測を実施した．夕食終了から就寝までの間隔が2時間未満の対象者を対照群とし, ロジスティック回帰分析を用いて解析を行った．高血圧に関して, 対照群に比し3-4時間, 4時間以上の群で, 有意に調整オッズ比が低下した．さらに21時以降の食事摂取者で, 高血圧の調整オッズ比は3-4時間空ける群で有意に低下し, 量反応性の関係が認められた．これらのことより, 夕食終了から就寝までの間隔を空けることが, 高血圧の予防につながる可能性が示唆された．

Journal of Japanese Society of Nutrition and Food Science


Lactobacillus plantarum OLL2712 regulates glucose metabolism in C57BL/6 mice fed a high-fat diet.

The aim of the present study was to determine the effect of oral administration of Lactobacillus plantarum OLL2712 (L. plantarum OLL2712) on glucose and lipid metabolism in mice with high-fat diet-induced obesity. Mice that had been administered 10(9) cfu heat-killed L. plantarum OLL2712 for 12 wk showed significant reduction of blood glucose levels in response to insulin. Furthermore, mRNA expression of interleukin-1β in adipose tissue and serum levels of nonesterified fatty acids in mice administered L. plantarum OLL2712 were significantly lower than those in control mice. These results indicate that L. plantarum OLL2712 regulates glucose metabolism.

Journal of Nutritional Science and Vitaminology


Dietary deoxynucleic acid induces type 2 T-helper immune response through toll-like receptor 9 in mice.

It has been shown that dietary nucleotides modulate immune response. Due to their unique properties in immune responses, nucleotides are used as immunonutrition in the field of clinical nutrition. In this study, we examined the effect of dietary deoxynucleic acid (DNA) on antigen (Ag)-specific immune response in ovalbumin (OVA)-immunized BALB/c mice and determined the mechanism using toll-like receptor 9 (TLR9) knock-out (KO) mice. BALB/c or TLR9 KO mice were fed control and 1% DNA diets and immunized with OVA. Spleen cells from OVA-immunized mice were stimulated with OVA in vitro, and the contents of IFN-γ and IL-4 in supernatants were measured by an ex vivo system. CD11c(+) dendritic cells were purified, and ability of cytokine induction to CD4(+) cells was examined. The level of OVA-specific IL-4 production in the DNA group was significantly higher than that in the control group. In contrast, the level of OVA-specific IFN-γ production in the DNA group was lower than that in the control group. The DNA diet decreased Ag-specific IL-4 production and enhanced Ag-specific IFN-γ production in TLR9 KO mice. CD11c(+) DCs from mice fed the DNA diet had a greater ability than CD11c(+) DCs from mice fed the control diet to induce the production of IL-4 from DO11.10 CD4(+) T cells. Dietary DNA increases Ag-specific IL-4 production and decreases IFN-γ production through a TLR9-dependent pathway. CD11c(+) dendritic cells are target cells in dietary DNA-induced immune regulation.


High phosphate diet reduces atherosclerosis formation in apolipoprotein E-deficient mice.

Although higher serum phosphate level is a risk factor for cardiovascular diseases in general population as well as chronic kidney disease patients, it has not been clarified whether higher phosphate can affect atherosclerotic plaque formation. In this study, we investigated the effect of prolonged-intake of different concentrations of phosphate on atherosclerosis formation using apolipoprotein E-deficient mice. Apolipoprotein E-deficient mice were fed with high fat diet including 0.6%, 1.2% or 1.8% phosphate. After 20-week treatment, atherosclerotic plaque formation in aorta in 1.8% phosphate diet group was unexpectedly less than that in the other groups. To elucidate mechanisms of suppression of plaque formation by high phosphate diet, we hypothesized that high phosphate diet may modify a profile of monocytes/macrophages suppressing plaque formation. We confirmed that elevated peripheral monocytes (CD11b+, F4/80+ cell numbers) in apolipoprotein E-deficient mice were decreased by feeding with 1.8% P diet. In addition, ex vivo study indicated that high dose of phosphate induced macrophage apoptosis. These observations suggest that excess phosphate intake decreased atherosclerosis formation, at least in part, by changing the profile of peripheral monocytes or inducing apoptosis of macrophages in apolipoprotein E-deficient mice.

Journal of Clinical Biochemistry and Nutrition


Suppression of oral tolerance by Lactococcus lactis in mice.

Although oral ovabumin (OVA) administration suppressed the antibody (Ab) response in OVA-immunized mice, Lactococcus lactis increased OVA-specific IgG2a in these mice. L. lactis increased the casein-specific IgG level in NC/Nga mice fed on a casein diet. The percentage of CD4(+)CD25(+) cells was increased in DO11.10 mice orally given OVA, but this increase of CD4(+)CD25(+) cells were suppressed in L. lactis-fed DO11.10 mice.

Bioscience, Biotechnology, and Biochemistry


Soy isoflavone equol perpetuates dextran sulfate sodium-induced acute colitis in mice.

The effects of the soy isoflavones, genistein, daidzein and equol, on experimental colitis were examined. Equol severely perpetrated dextran sulfate sodium (DSS)-induced colitis as evaluated by the weight loss. Production of the anti-inflammatory cytokine, IL-10, from T cells was decreased in the equol-treated mice. The results show that the soy isoflavone, equol, played an important role in the inflammatory response in the gastrointestinal tract.


Vimentin binds IRAP and is involved in GLUT4 vesicle trafficking.

Insulin-responsive aminopeptidase (IRAP) and GLUT4 are two major cargo proteins of GLUT4 storage vesicles (GSVs) that are translocated from a postendosomal storage compartment to the plasma membrane (PM) in response to insulin. The cytoplasmic region of IRAP is reportedly involved in retention of GSVs. In this study, vimentin was identified using the cytoplasmic domain of IRAP as bait. The validity of this interaction was confirmed by pull-down assays and immunoprecipitation in 3T3-L1 adipocytes. In addition, it was shown that GLUT4 translocation to the PM by insulin was decreased in vimentin-depleted adipocytes, presumably due to dispersing GSVs away from the cytoskeleton. These findings suggest that the IRAP binding protein, vimentin, plays an important role in retention of GSVs.

Biochemical and Biophysical Research Communications


Extracts of common buckwheat bran prevent sucrose digestion.

Buckwheat has been shown to have various health benefits such as reduction of hypertension and improvement of hypercholesterolemia; however, its effect on diabetes has not been fully elucidated. In this study, buckwheat bran extracts (BBE) inhibited sucrase activity in vitro more effectively than buckwheat. Balb/c mice pretreated with BBE showed dose-dependent reductions of blood glucose, greater than those observed with control mice, within 60 min following oral sucrose administration. Blood glucose levels in mice pretreated with buckwheat extracts were also significantly lower compared to those in control mice within 30 min following oral administration of sucrose. However, rutin, one of the abundant polyphenols of BBE, did not lower blood glucose level. Our data indicate that components of BBE other than rutin have inhibitory activity against sucrase in vivo. These results suggest that BBE could have beneficial effects on diabetes.

Journal of Nutritional Science and Vitaminology


Does food intake and life style relate to the prevalence of allergic disease?

食物摂取および生活習慣とアレルギー疾患との関連について

Journal of rehabilitation and health science


Long-term treatment with hyperbaric air improves hyperlipidemia of db/db mice.

Hyperbaric air (HBA) is used to improve healing of wounds including diabetic ulcer. The aim of this study was to clarify the effects of HBA exposure on lipid and glucose metabolism in db/db mice. HBA did not influence the weight of db/db mice. Serum levels of free fatty acid and triglyceride, but not glucose and insulin, were significantly decreased after 6 weeks of treatment with HBA. The mRNA expressions of CPT-1, PPAR and PGC-1 genes, which are related to lipid metabolism, were significantly up-regulated in the muscle and liver. Increases in TNF and MCP1 mRNA, which impaired lipid metabolism, were also attenuated by HBA treatment. These results suggest that exposure of HBA could have beneficial effects on lipid metabolism in patients with type 2 diabetes mellitus.

The Journal of Medical Investigation : JMI


栄養と免疫機能—非必須栄養素，低栄養状態，過栄養状態と免疫—

It is known that nutritional state crucially affects immune function. In recent years, the contributionof the diet to the optimal working of the immune system has become wildly appreciatedand the influence of different dietary components on specific aspects of immune function has beenextensively studied. Soy isoflavone genistein suppresses antigen-specific immune response inBALB/c mice and suppresses development of atopic-like dermatitis in NC/Nga mice. In other soyisoflavone equol enhances antigen-specific IgE production via IL-13-mediated pathway. Further,equol exacerbates colitis of dextran sulfate sodium-treated mice. Therefore, immune stimulatoryeffects are strikingly different among soy isoflavones. In this reviews, in addition of the isoflavone,we overview the effects of dietary nucleic acid and protein-deficiency on antigen-specific immuneresponses. Furthermore, we present hot topics researches in the field of obesity and T cellfunction.


The Soy isoflavone equol enhances antigen-specific IgE production in ovalbumin-immunized BALB/c mice.

Although an immunomodulatory role of the soy isoflavone genistein has been demonstrated, the effects of other soy isoflavones on induction of antigen (Ag)-specific immune responses are not known. In this study, we therefore investigated the effects of daidzein and equol on ovalbumin (OVA)-specific T cell and B cell responses in BALB/c mice. Mice that had been treated with 20 mg/kg equol showed a significantly higher level of OVA-specific IgE than control mice. Levels of interferon (IFN)-gamma and interleukin (IL)-4 production were not different between the control and equol groups. However, IL-13 production level in mice administered 20 mg/kg equol was significantly higher than that in control mice. Strong induction of OVA-specific IgE production by equol was also observed in ovariectomized BALB/c mice, suggesting that the immunomodulatory effect of equol is not affected by endogenous estrogen.

Journal of Nutritional Science and Vitaminology


Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes.

In adipocytes and myocytes, insulin stimulation translocates glucose transporter 4 (Glut4) storage vesicles (GSVs) from their intracellular storage sites to the plasma membrane (PM) where they dock with the PM. Then, Glut4 is inserted into the PM and initiates glucose uptake into these cells. Previous studies using chemical inhibitors demonstrated that myosin II participates in fusion of GSVs and the PM and increase in the intrinsic activity of Glut4. In this study, the effect of myosin IIA on GSV trafficking was examined by knocking down myosin IIA expression. Myosin IIA knockdown decreased both glucose uptake and exposures of myc-tagged Glut4 to the cell surface in insulin-stimulated cells, but did not affect insulin signal transduction. Interestingly, myosin IIA knockdown failed to decrease insulin-dependent trafficking of Glut4 to the PM. Moreover, in myosin IIA knockdown cells, insulin-stimulated binding of GSV SNARE protein, vesicle-associated membrane protein 2 (VAMP2) to PM SNARE protein, syntaxin 4 was inhibited. These data suggest that myosin IIA plays a role in insulin-stimulated docking of GSVs to the PM in 3T3-L1 adipocytes through SNARE complex formation.


Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression through protein kinase A pathway and prevents inflammatory adipokine expression.

Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that has been used as a drug injected subcutaneously for treatment of type 2 diabetes. Many studies have revealed molecular targets of Ex-4, but its influence on adipokines has not been determined. Our study showed that Ex-4 induced secretion of adiponectin into the culture medium of 3T3-L1 adipocytes. This effect of Ex-4 is due to increased adiponectin mRNA level through the GLP-1R. Both forskolin and 3-isobutyl-1-methylxanthine (IBMX), which may finally elevate cyclic adenosine monophosphate (cAMP) concentration, prevented the induction of adiponectin expression by Ex-4. Moreover, H89, a protein kinase A inhibitor, blocked the effect of Ex-4 on adiponectin. On the other hand, Ex-4 decreased the mRNA levels of inflammatory adipokines. The results indicate that Ex-4 directly promotes adiponectin secretion via the protein kinase A pathway in 3T3-L1 adipocytes and may ameliorate insulin resistance.


Hyperphosphatemia and cardiovascular disease

Hyperphosphatemia has been known as a risk factor for cardiovascular disease particularly inchronic kidney disease patients. Hyperphosphatemia can be involved in the calcification of vascularsmooth muscle cells, resulting in M¨onkeberg medial calcific sclerosis which is a type of arteriosclerosis.However, it has not been clarified whether hyperphosphatemia can deteriorate endothelialfunction and can be a risk factor of atherosclerosis. Our recent study demonstrated that hyperphosphatemiaincreased oxidative stress and decreased nitric oxide production in endothelial cells.In addition, hyperphosphatemia attenuated endothelium-dependent vasodilation reaction. Theseobservations suggest that hyperphosphatemia may cause endothelial dysfunction, and be an importantfactor for progression of atherosclerosis as well as vascular calcification. Positive associationbetween hyperphosphatemia and cardiovascular disease may be explained by the dual harmfuleffects of phosphorus on the vessels.


The amount of soy products consumed in Japan is much greater than that in Western countries. Recent evidence indicates that soy isoflavones play a beneficial role in obesity, cancer, osteoporosis, and cardiovascular disease. The soybean isoflavone genistein is present at high levels in soy products. Genistein is structurally similar to 17beta-estradiol (E2), and genistein has been suggested to be act as E2 or an antagonist against E2. Genistein suppresses antigen-specific immune response in vivo and lymphocyte proliferation response in vitro. However, genistein enhances the cytotoxic response mediated by NK and cytotoxic T cells and the cytokine production from T cells. Thus, the effect of genistein on immunity is immune cell-dependent. Due to its unique effect on immune function, genistein has been used for the treatment of the diseases in animal models and it has been found that genistein inhibits allergic inflammatory responses. In this review, we summarize current studies related to the effect of isoflavone genistein on the immune system.


Nucleoside and nucleotide mixture OG-VI rescues cytotoxicity induced by chemotherapeutic agents in intestinal-like epithelial cell.

Immune cells and cells undergoing rapid turn-over can obtain exogenous nucleotides via salvage synthesis. We evaluated whether or not the balanced nucleoside and nucleotide mixture OG-VI, could rescue intestinal epithelial-like Caco-2 cells from the cytotoxic effects of several chemotherapeutic agents, in the presence and absence of glutamine (Gln). Cells were exposed to 5-fluorouracil (5FU), methotrexate (MTX) or 6-mercaptopurine (6MP), after which proliferation and cell cycle analyses were performed. Following exposure to the chemotherapeutic agents, we observed that cells treated with OG-VI proliferated well, whereas those without the supplement did not proliferate. Furthermore, following treatment with either 5FU or MTX, we observed that the number of cells in the G0/G1 phase decreased and those in the S phases increased. However, these cell cycle alterations were prevented by the addition of OG-VI. With the exception of 6MP-treated cells, we did not observe any effects on proliferation or cell cycle regulation that could be ascribed to the presence of Gln. Thus, we have demonstrated that OG-VI rescues cells from the cytotoxic effects of several chemotherapeutic agents.


Maturational arrest of thymocyte development is caused by a deletion in the receptor-like protein tyrosine phosphatase κ gene in LEC rats

The Long-Evans Cinnamon (LEC) rat has a spontaneous mutation, T helper immunodeficiency (thid), which causes a markedly reduced CD4(+) thymocyte population. Here we positionally clone the locus and identify a deletion in the gene encoding a receptor-like protein tyrosine phosphatase kappa (Ptprk) that led to complete loss of the transcript. The rat Ptprk gene exhibits 98% identity with the human and mouse counterparts and is expressed most abundantly in the CD4(-)CD8(-) double-negative stage. The downregulation of Ptprk in mouse immature thymocytes by RNA interference mimicked the thid phenotype. These results indicate that thid maps to the Ptprk locus and that functional Ptprk is crucial for lineage commitment or progression of CD4(+) T cells. We also found that Ptprk appears to function in parallel with or downstream of Th-POK/cKrox (also known as ZBTB7B), a master regulator of T cell lineage decision.


Polymethoxylated flavone sudachitin is a safe anticancer adjuvant that targets glycolysis in cancer-associated fibroblasts.

Sudachitin is a polymethoxylated flavone found in the peel of , a unique specialty citrus fruit in Tokushima Prefecture, Japan. Previous reports have demonstrated that sudachitin has anti-inflammatory and metabolic regulatory activities. However, to the best of our knowledge, no studies have explored whether sudachitin can act as an antitumor therapeutic agent by regulating metabolic functions in the tumor microenvironment. In the present study, cell proliferation and cytotoxicity assays were used to determine whether sudachitin inhibited the growth of liver cancer and pancreatic carcinoma, cholangiocarcinoma and colorectal cancer cells and to compare its toxicity against normal fibroblasts and induced cancer-associated fibroblasts (CAFs). Using lactate assays and reverse transcription-quantitative PCR, the effects of sudachitin on glycolysis in CAFs were investigated. The effects of CAFs on malignant tumor cells were evaluated using cell proliferation, wound healing and invasion assays. As result, sudachitin inhibited various types of tumor cells with different half-maximal inhibitory concentrations. Treatment with 50 µM sudachitin for 48 h suppressed tumor and CAFs proliferation but was not cytotoxic against normal fibroblasts. This dose also inhibited glycolysis in CAFs and, thus, diminished their pro-tumorigenic activities. Overall, the present study revealed that sudachitin has promise as a safe and widely available natural antitumor adjuvant.