Low levels of serum vitamin D have been shown to accelerate progression of osteoarthritis. However, the role of vitamin D in articular cartilage degradation and osteoarthritis development is still unclear. This study investigated the effects of vitamin D on articular cartilage degradation by testing matrix metalloproteinase (MMPs) activities in articular cartilage using the rat vitamin D deficiency model at the animal level and rat articular chondrocytes at the cell level. The in vivo study showed vitamin D deficiency increased the expressions of MMP-9 and MMP-13 in rat articular cartilage, and the increase was inhibited by 1α,25(OH)₂D₃ supplementation. The increased production of MMP-9 and MMP-13 in the articular chondrocytes induced by tumor necrosis factor-α (TNF-α) or phorbol-12-myristate-13-acetate (PMA) was significantly suppressed by concomitant treatment with 1α,25(OH)₂D₃ in vitro. The increased level of C-telopeptide of type II collagen (CTX-II) induced by TNF-α or PMA was also significantly suppressed by concomitant treatment with 1α,25(OH)₂D₃ in vitro. Thus, vitamin D intake may inhibit MMP activities and take part in the process of articular cartilage degeneration and osteoarthritis progression.

Food allergy prevalence is increasing all over the world. Recent epidemiologic studies have shown the link between vitamin D₃ insufficiency and food allergy occurrence. In this study, we investigated the effect of supplementation with cholecalciferol, a widely used form of vitamin D₃, on food allergy using an experimental mouse model. In wild-type BALB/c mice which were sensitized and challenged with an experimental allergen, ovalbumin, a clinical symptom of food allergy, diarrhea, was significantly induced with the elevation of immunoglobulin E level and the increases of T helper 2 cytokine productions, such as interleukin-4, -5, and -13 (p<0.05), whereas no change in T helper 1 cytokine production, such as interferon-γ, was observed. It was also found that cell population of CD69⁺ CD4⁺ T cells was increased slightly in spleen and significantly in the mesenteric lymphnode with the diarrheal symptom (p<0.05). Treatment of cholecalciferol reduced the allergic diarrhea (p<0.05) with the decreasing tendency of CD69⁺ CD4⁺ T cells, suggesting that the cell population might be associated with the attenuating effect of cholecalciferol on diarrhea occurrence, although immunoglobulin E levels and cytokine productions were not significantly altered by the treatment of cholecalciferol. When given the mice anti-CD69 mAb treatment, significant improvement of allergic diarrhea symptom was observed (p<0.05), accompanying the decrease of CD69⁺ CD4⁺ T cells which suggested the contribution of these cells to the diarrhea symptom. Taken together, we suggest that administration of cholecalciferol might be useful to suppress symptomatic food allergy in association with the decrease of CD69⁺ CD4⁺ T cells.

We have previously reported a positive correlation between the body mass index (BMI) of mothers and the Kaup index of infants at birth and that this correlation may have a stronger influence on the male infants, born to older mothers. Therefore, in this study, we aimed to clarify the correlation between maternal age and gender of the infants as maternal BMI and the Kaup index of infants from birth till 18 mo of age. This study was conducted from April 2010 to September 2011 in Japan. Public health nurses and registered dietitians interviewed the mothers individually under anonymous conditions, and they transferred the required information from the maternity passbook at the 18-mo health checkup. In male infants, significant positive correlations were demonstrated between maternal BMI at the beginning of pregnancy and the Kaup index of infants in mothers older than 35 y when the infants were at birth, at 4 mo and at 18 mo old. In female infants, there was no correlation between maternal BMI and the Kaup index of infants at birth. However, significant positive correlations were demonstrated between maternal BMI and the Kaup index of infants in mothers in their 20s and older than 35 y old when the infants were 4 and 18 mo old. Women who plan on pregnancy and medical professionals need to know that the maternal physique at the beginning of pregnancy affects the physique of the infants at birth and at 4 mo and 18 mo old by gender of the infants.

Microglia are immunocompetent cells of the central nervous system whose function is to preserve nervous tissue homeostasis; however, under inflammatory conditions, they are associated with tissue damage. Dietary restriction is a nutritional intervention used to delay the onset of chronic disease and inflammation, in addition to improving the functions of the immune system. The aim of this study was to analyze the effect of dietary restriction on microglial expression of MHC molecules. Adult female and male BALB/c mice were fed ad libitum (controls) or kept under dietary restriction (30% reduction in food intake) for 4 wk. Purified brain mononuclear cells were analyzed by flow cytometry staining for CD45, CD11b, MHC-I and MHC-II. Our results show that female animals under dietary restriction had a significant increase in MHC-I expression in microglia (mean fluorescence intensity=7,854 (control) vs. 10,628 (diet-restricted), arbitrary units; p=0.0108), along with increased frequencies of lymphocytes compared to controls (1.39% (control) vs. 7.85% (diet-restricted); p=0.0175), whereas male animals did not show significant differences between groups. Our data suggest a differential effect for dietary restriction on female and male animals, with this nutritional regimen predominantly affecting females. Increased expression of MHC-I by diet-restricted microglia may play a role in maintaining tolerance in the absence of antigenic stimulation.

The plasma concentrations of mineral (sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), phosphorus (P), and zinc (Zn)) are kept within narrow ranges to maintain homeostasis; hence, it is difficult to use them as indicators of nutritional status. We selected the excretion of these minerals in the second voided fasting early morning urine (EMU) as potential indicators of nutritional status. We previously reported that Na restriction caused a negative balance of Ca and Mg. Therefore, Na restriction can cause changes in EMU-minerals. This study aimed to examine the relationship between dietary Na restriction and urinary mineral excretion. The study lasted for 21 d, including 16 d of balance period and 3 d of recovery period. The participants (11 healthy young women) were divided into the Na restriction group (n=5) (NaCl: 6 g/d) and control group (n=6) (NaCl: 12 g/d). The Na restriction group changed to the control diet (NaCl: 12 g/d) during only the recovery period. The EMU-Na, Ca, Mg, P and Zn in the Na restriction group significantly decreased compared with that of the control group. The EMU-Na, K, Ca, Mg, and Zn in the group with NaCl intake of 6 g/d significantly decreased compared with that of the group with NaCl intake of 12 g/d (in the Na restriction group). We conclude that the decrease in excretion of Na, Ca, Mg and Zn in the EMU can lead to Na restriction. This result can serve as basis when considering EMU as an indicator of mineral status.

Malnutrition is a severe problem among elderly residents living in long-term care facilities. A simple and accurate estimation for total daily energy expenditure (TEE) is required in order to provide them with an adequate amount of food. The purpose of this study was to validate a physical activity assessment tool for estimating TEE among elderly residents. The data of 58 subjects aged 69-99 y were analyzed in this study. The one-day physical activity recall was filled out by facility staff for a typical day. TEE was measured by the doubly labeled water (DLW) method (TEE_DLW), and predicted by one-day physical activity recall using the basal metabolic rate (pTEE_BMR) and body weight (pTEE_BW). The TEE_DLW, pTEE_BMR and pTEE_BW were 1,129±196 kcal/d, 1,186±251 kcal/d and 1,326±236 kcal/d, respectively. In a regression model, body weight, movement means and sex explained 39.0% of the variance in the difference between pTEE_BMR and TEE_DLW (p<0.05). Percentage of fat mass, body weight, and Barthel Index except mobility explained 47.3% of the variance in the difference between pTEE_BW and TEE_DLW (p<0.05). The current results suggested that pTEE_BW is not recommended to estimate TEE because the error depends on body size, and pTEE_BMR was significantly correlated with TEE_DLW but also included systematic errors in elderly residents. In order to improve the accuracy of the present assessment to estimate TEE, it is necessary to establish a new equation of basal metabolic rate for elderly residents and consider sex and movement means to estimate TEE.

1-Deoxynojirimycin (DNJ) has been known as a potent α-glucosidase inhibitor from mulberry leaves and considered beneficial in prevention of type 2 diabetes. Due to limited amount of DNJ in mulberry leaves, recent studies have focused in finding alternative source that can produce higher amount of DNJ. Previously, we produced a high DNJ-containing culture medium from Bacillus amyloliquefaciens AS385 and constructed a concentration method of bacterial culture medium using cation exchange column. However, less complicated concentration procedure is necessary to save time and cost during the large-scale production. Therefore, we developed a simpler concentration method using anion exchange resin to yield B. amyloliquefaciens AS385 culture broth powder (CBP; 1% DNJ) and evaluated the physiological effects of 5-wk dietary CBP intake in C57BL/6J mice. CBP intake tended to suppress the elevation of blood glucose level during oral glucose tolerance test. Moreover, CBP intake significantly lowered the fasting plasma glucose level and white adipose tissue mass. Next, we evaluated the absorption and distribution of DNJ in mice organs after daily CBP intake. We found detectable amount of DNJ in organs with intestine and kidney as the major targeted organs. We concluded that the DNJ content in CBP is absorbed from digestive tract, distributed and accumulated in organs, which most likely to contribute to the alteration of blood glucose regulation and adiposity in C57BL/6J mice. Our study was the first to report the physiological effects of CBP produced from B. amyloliquefaciens AS385 and the organ distribution of DNJ from CBP.

We previously reported that dietary heat-killed Lactobacillus brevis SBC8803 affects sleep in mice and humans. The present study examined whether SBC8803 improves psychophysiological stress-induced chronic sleep disorders (CSD) using a mouse model characterized by disrupted circadian rhythms of wheel-running activity and sleep-wake cycles. Mice were fed with a diet supplemented with 0.5% heat-killed SBC8803 for 6 wk and imposed stress-induced CSD for last 2 wk. Dietary SBC8803 suppressed the reduction in wheel-running activity induced by CSD. Electroencephalography (EEG) revealed that SBC8803 significantly restored wakefulness and increased non-rapid eye movement (NREM) sleep during the second half of the active phase during CSD. The CSD-induced reduction in EEG slow wave activity, a marker of NREM sleep intensity, during the beginning of the inactive phase was significantly improved by SBC8803 supplementation. These findings suggest that dietary heat-killed SBC8803 confers beneficial effects on insomnia and circadian sleep disorders induced by psychophysiological stress.

Dysfunction of vascular endothelial cells causes the risk of thrombosis. Aim of this study is to evaluate the antithrombotic effect of Okinawa mozuku (brown seaweed, Cladosiphon okamuranus) extract by using cultured vascular endothelial cells and rat carotid arterial thrombosis model induced by ferric chloride (FeCl₃). The cell line (TKM-33) established from human umbilical vein endothelial cells were cultured with or without Okinawa mozuku extract. After incubation for 24 h, the conditioned medium was collected to evaluate urokinase-type plasminogen activator (u-PA) activity. Next, rats were fed with water or water containing 5% of Okinawa mozuku extract for 8 wk. After 8 wk of treatments, the rats were provided for the carotid arterial thrombosis model, and fibrinolytic factor and coagulation factor in blood were measured. Okinawa mozuku extract significantly augmented u-PA activity in the conditioned medium. The decrease of carotid artery blood flow induced by 40% FeCl₃ injury in rats fed with Okinawa mozuku extract was less than that in control rats. Thus, oral administration of Okinawa mozuku extract prevented thrombus formation in this model. Oral administration of Okinawa mozuku extract significantly increased u-PA activity in euglobulin fraction, compared with control group. On the other hand, platelet aggregation activity, activated partial thromboplastin time, and active PAI-1 level in plasma exhibited no significant differences between control and Okinawa mozuku groups. These results indicate that oral administration of Okinawa mozuku enhances fibrinolytic activity in plasma and prevents thrombus formation which is induced by injury of vascular endothelial cells.

The purpose of the study was to examine the association of the frequencies of milk and dairy product consumption with subjective sleep quality during the training period in Japanese elite athletes. In this cross-sectional study, 682 Japanese elite athletes who were candidates for the 2016 Rio Olympic Games underwent medical evaluations at the medical center of The Japan Institute of Sports Sciences. Self-reported questionnaires were used to collect information on demographics and lifestyle (age, height, weight, sports, presence of milk allergy, smoking and drinking habits), subjective sleep quality (good, normal, or poor), bedtime, waking time, sleep duration, and frequencies of milk and dairy product consumption. Data from 679 athletes (379 men, 300 women) without milk allergy, were analyzed. Based on the frequencies of both milk and dairy product consumption, the athletes were divided into three groups: low (0-2 d/wk), middle (3-5 d/wk), and high (6-7 d/wk). Multiple logistic regression models showed that in comparison with the low milk consumption group, the middle [OR (95% CI): 0.48 (0.26-0.91)] and high groups [0.38 (0.21-0.71)] were significantly associated with a lower risk of decrease in subjective sleep quality (0: good, 1: normal or poor) only in women, after adjusting for possible confounders, such as smoking, drinking habits, and sleep duration. Accordingly, the present study elucidated that a greater frequency of milk consumption was significantly associated with a lower risk of decrease in subjective sleep quality, during training periods in women.

Zinc in various therapeutic doses was used on patients suffering from oral mucositis during cancer treatment. A meta-analysis was conducted to probe the role of oral zinc as a possible treatment option for oral mucositis. A literature search was done using PubMed, EBSCO, Cochrane, MedLine, ScienceDirect, ResearchGate and Google Scholar with key words. The analysis was directed to recognize and identify the use of zinc supplementations at a confidence interval (CI) 95% with p value significance taken as <0.05. A total number of 21,428 articles was retrieved. After thorough screening and assessment of the eligibility criteria, 10 articles were included in qualitative and quantitative analysis in the study. The 10 articles constituted a total sample size of 299 in the case group and 294 in the control group. Oral zinc doses used were 25 mg, 30 mg, 50 mg and 220 mg capsules and mouthwash of 0.2% zinc, as well as 0.5 g of granules dissolved in 5% sodium alginate solution. Two studies showed no significance, with the overall effect 1.61. Eight studies favored zinc over a placebo with an overall effect size of −0.89 at 95% CI of −1.08 and −0.70 which was statistically significant (Z=9.27, p<0.00001). This analysis suggests that zinc usage has shown significant reduction in the severity of oral mucositis but not prevention. The onset of the reaction was delayed and hastened healing. Pharyngeal mucositis, pain and quality of life of the individuals received no effect from zinc therapy.

The intake of polyphenols among Japanese has been estimated in several adult populations, but there has been no information regarding their intake among young adults, especially in those in their twenties. We conducted a food frequency questionnaire (FFQ)-based dietary assessment four times a year (once in each season) among Japanese university students and evaluated the total polyphenol intake across and within seasons. Forty-nine subjects (aged 20.7±0.6 y) completed our FFQ regarding polyphenol intake in February, May, August, and November 2016. We then calculated their total polyphenol intake using our polyphenol content database. The mean intake of total polyphenol across the seasons was 567±236 mg/d, which was largely sourced from beverages (62%). No significant differences were found in the total polyphenol intake or polyphenol intake from beverages among the four seasons. By contrast, we observed significant seasonal differences in the subjects’ polyphenol intake from food; the polyphenol intake from food in February (255 mg/d) was significantly higher than that in May (215 mg/d), August (187 mg/d) and November (196 mg/d) (p<0.0001). These findings should assist in future estimations of dietary polyphenol intakes that consider differences according to age and season.

We investigated the combined effects of ‘Benifuuki,’ a tea cultivar that contains O-methylated catechins like epigallocatechin-3-O-(3-O-methyl) gallate, and quercetin on hepatic fat accumulation in male Sprague-Dawley rats fed a high-fat, high-cholesterol diet for 15 d. Rats given ‘Benifuuki’+quercetin had synergistically lower liver triglyceride (TG) level compared with rats given ‘Benifuuki’ or quercetin alone. Compared with ‘Benifuuki’ or quercetin alone, supplementation with ‘Benifuuki’+quercetin resulted in a low level of fatty acid synthase (FAS) and stearoyl-CoA desaturase1 (SCD1) gene expression levels. These results suggest that the combination of ‘Benifuuki’ and quercetin has greater liver lipid-lowing effects than that of ‘Benifuuki’ or quercetin alone. The liver TG-lowing effect of combination of ‘Benifuuki’ with quercetin may be partially mediated by the suppression of lipogenesis. The combination of ‘Benifuuki’ and quercetin suppresses hepatic fat accumulation in high fat high cholesterol diet fed rats, showing a new trend of ‘Benifuuki’ as synergist with quercetin.

Rubiscolin-6 (Tyr-Pro-Leu-Asp-Leu-Phe) is produced by a pepsin digest of spinach d-ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and known to act as an agonist on δ-opioid receptor. Here, we showed that administration of rubiscolin-6 reduced immobility time in the tail suspension test in restraint-stressed mice without effect on locomotor activity. The antidepressant-like effect of rubiscolin-6 was blocked by a δ-opioid receptor antagonist, naltrindole. These results indicate that rubiscolin-6 exerts antidepressant-like effect through activation of δ-opioid receptor.

Our previous study showed that the subcutaneous administration of auraptene (AUR) suppresses inflammatory responses including the hyperactivation of microglia in the substantia nigra (SN) of the midbrain of lipopolysaccharide-induced Parkinson’s disease (PD)-like mice, as well as inhibits dopaminergic neuronal cell death in this region. We also showed that the oral administration of the dried peel powder of Citrus kawachiensis, which contains relatively high amounts of AUR, suppresses inflammatory responses including the hyperactivation of microglia in the systemically inflamed brain. In the present study we showed that the oral administration of this dried peel powder successfully suppressed microglial activation and protected against dopaminergic neuronal cell death in the SN, suggesting its potential as a neuroprotective agent for the treatment of patients with PD.