Resveratrol and piceid enhance efferocytosis by increasing the secretion of MFG-E8 in human THP-1 macrophages.

The process of apoptotic cell clearance by phagocytes, known as efferocytosis, plays an essential role in maintaining homeostasis. Defects in efferocytosis can lead to inflammatory diseases such as atherosclerosis and autoimmune disorders. Therefore, the maintenance and promotion of efferocytosis are considered crucial for preventing these diseases. In this study, we observed that resveratrol, a representative functional food ingredient, and its glycoside, piceid, promoted efferocytosis in both human THP-1 macrophages differentiated with phorbol 12-myristate 13-acetate and peritoneal macrophages from thioglycolate-elicited mice. Resveratrol and piceid significantly increased mRNA expression and protein secretion of MFG-E8 in THP-1 macrophages. Furthermore, the activation of efferocytosis and the increment in MFG-E8 protein secretion caused by resveratrol or piceid treatment were canceled by MFG-E8 knockdown in THP-1 macrophages. In conclusion, we have demonstrated for the first time that resveratrol and piceid promote efferocytosis through the upregulation of MFG-E8 excretion in human THP-1 macrophages.

Bioscience, Biotechnology, and Biochemistry


Associations between dietary diversity and high sensitive C-reactive protein among Japanese workers: findings of a cross-sectional and longitudinal study.

These findings suggest that, in male Japanese workers, higher dietary diversity might be important for maintaining a low inflammatory status.

In the cross-sectional analysis, the hs-CRP concentration in male participants was significantly lower in those who had a high QUANTIDD score (adjusted mean [95% CI]: 0.074 [0.009-0.140] mg/dL in the lower group vs. 0.038 [-0.029-0.105] mg/dL in the higher group, p-value = 0.034). In the longitudinal analysis, the hs-CRP concentration of male participants also tended to be lower in those with higher QUANTIDD scores (p-value = 0.103). In both the cross-sectional and longitudinal analyses in women, there was no significant difference between the lower and higher QUANTIDD score groups.


Flavonoids, nobiletin, heptamethoxyflavone, and genistein enhance antigen-presenting cell function in vitro


Associations between dietary diversity and dyslipidemia among Japanese workers: cross-sectional study and longitudinal study findings.

The results of cross-sectional analysis in this study suggest that the higher diversity of diet might reduce the presence of dyslipidemia in men and the results of longitudinal analysis suggest that a moderate DDS might reduce the risk of dyslipidemia in women. Further studies are needed since the results of cross-sectional and longitudinal analyses in this study were inconsistent.

Cross-sectional analysis showed that the highest DDS reduced the odds of dyslipidemia in men (OR [95% CI] in Tertile 3: 0.67 [0.48-0.95], p value = 0.023). In longitudinal analysis, a moderate DDS reduced the risk of dyslipidemia (OR [95% CI] in Tertile 2: 0.21 [0.07-0.60], p value = 0.003) in women.


Changes in higher-level functional capacity during the COVID-19 pandemic among older adults living in Japan.

The findings suggest an association of the COVID-19 pandemic with a decrease in higher-level functional capacity, especially in Social Role, among older adults living in Japan. J. Med. Invest. 71 : 66-74, February, 2024.

The Journal of Medical Investigation : JMI


The Soy Isoflavone Genistein Enhances IFN-γ-Induced PD-L1 Expression in B16F1 Melanoma Cells in Vitro


Soy isoflavone genistein attenuates the efficacy of immune checkpoint therapy in C57BL/6 mice inoculated with B16F1 melanoma and a high PD-L1 expression level reflects tumor resistance.

cells and the concentrations of interferon-γ and tumor necrosis factor-α in tumor tissue were not different among the experimental groups. A significant difference was also not found in microbe composition. Interestingly, a high expression level of PD-ligand (L)1 closely reflected the outcome of therapy by genistein or anti-PD-1 antibody. The study showed that a combination of genistein treatment does not improve the effect of immune blockade therapy. It also showed that a high PD-L1 expression level in tumors is a good prediction maker for the outcome of tumor therapy.

Journal of Clinical Biochemistry and Nutrition


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


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.


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


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 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.


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.


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.


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.


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


日本人勤労者の大豆製品摂取行動がメタボリック症候群発症に与える影響の検証

日本人勤労者の大豆製品摂取行動がメタボリック症候群発症に与える影響の検証


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.