A high intake of green leafy vegetables rich in antioxidative nutrients such as vitamin C and β-carotene may protect against the risk of type 2 diabetes. Measurement of the circulating nutrient concentrations can indicate the nutrient status more directly, and vitamin C and carotenoids are recognized as good biomarkers for the intake of fruits and vegetables. The aim of this study was to investigate the relationships between serum antioxidative vitamin concentrations and type 2 diabetes in Japanese subjects. The study subjects comprised 506 men and 493 women who first underwent anti-aging health checks at Tokai University Tokyo Hospital. Serum concentration of vitamin (V) A, VC, α-tocoferol, β-carotene, VB12, folate, ferritin and homocysteine, and fasting plasma glucose and HbA1c were used for analysis. Low levels of β-carotene and VC were significantly associated with dysglycemia. Diabetic subjects showed significantly decreased β-carotene and VC levels, and multivariate analyses suggested that low levels of β-carotene and VC were factors related to diabetes. Low levels of β-carotene and VC are significantly related to dysglycemia/type 2 diabetes, and encouraging people at a higher risk of diabetes to take more green vegetables may be useful as a dietary intervention to improve the antioxidative vitamin status and dysglycemia.

Acerola (Malpighia emarginata DC.) is a fruit containing abundant ascorbic acid (AsA) and numerous functional phytochemicals. We previously reported that the intake of acerola juice increased the absorption of AsA in plasma of healthy Japanese subjects. The functional phytochemicals in acerola may influence the intestinal epithelial cells to increase the cellular uptake of AsA. Therefore, in this study, we compared the AsA uptake into Caco-2 cells between AsA alone and that in acerola juice at the same concentration using a human intestinal model. Caco-2 cells were incubated with 3 mM AsA and 3 mM AsA in acerola juice. Intracellular AsA contents gradually increased until 24 h upon incubation with both AsA alone and AsA in acerola juice; however, these contents when incubated with AsA in acerola juice, were significantly higher than those incubated with AsA alone at 2, 3, 4, 8, and 24 h. Furthermore, the mRNA expression level of the sodium-dependent vitamin C transporter (SVCT) 1 was significantly higher in the cells incubated with AsA in acerola juice than those incubated with AsA alone. Moreover, polyphenols such as cyanidin-3-glucoside chloride and quercetin enhanced the SVCT1 gene expression in Caco-2 cells. Collectively, these results suggest that acerola polyphenols enhances the SVCT1 gene expression in Caco-2 cells and promotes AsA uptake.

Current studies focused on the effects of all-trans-retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were extracted aseptically from the quadriceps femoris of the knee joint of rats, and then incubated in medium containing 10% neonate bovine serum for 24 h adaptive culture. We first measured variations of correlation factors in synovium at 24, 48, 72, 96 and 120 h in control medium or in medium containing 20 ng/mL tumor necrosis factor alpha (TNF-α) (TNF-α-experiment). Then, we investigated the synovium exposed to three ATRA concentrations after 48 h incubation (ATRA-experiment). The effects of ATRA on synovitis were evaluated by observing the expression of inflammatory cytokines, angiogenic factors and the production of proteases in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and apoptosis and autophagy. In TNF-α-experiment, the secretion of nitric oxide (NO), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) increased significantly after TNF-α stimulation without pathological damage to the synovium. Hence, we successfully obtained the synovial explants model, which had longer inflammatory response time. In the ATRA-experiment, ATRA suppressed the secretion of IL-6 and NO, downregulated the NF-κB P65 and Bcl-2, increased levels of autophagy marker protein LC3, but different doses of ATRA showed inconsistent regulatory effects on VEGF and MMP-9. In short, ATRA inhibited TNF-α induced synovitis by the regulation of inflammatory cytokines and inhibiting NF-κB signal transduction and potentially promoting autophagy, apoptosis and angiogenesis, displaying its role in alleviating synovial inflammation in patients with RA.

This study was conducted to investigate the effect of dietary porous ZnO supplementation on the growth performance, inflammatory cytokines and tight junction’s gene expression in weaned piglets. A total of 192 weaned piglets were randomly allocated to 4 experimental groups (n=48/group) and fed, during 14 d, with one of the following dietary treatments: 1) basal diet (NC); 2) basal diet with 3,000 mg/kg of conventional ZnO (PC); 3) basal diet with 750 mg/kg of porous ZnO (low inclusion porous ZnO, LP-ZnO); 4) basal diet with 1,500 mg/kg porous ZnO (high inclusion porous ZnO, HP-ZnO). Results showed that dietary supplementation with regular ZnO or porous ZnO (750 and 1,500 mg/kg) improved average daily gain (ADG), feed to gain ratio (F/G) and jejunum morphology, while decreasing diarrhea incidence. Compared with the NC group, porous ZnO at both doses (750 or 1,500 mg/kg) increased serum alkaline phosphatase (ALP), immunoglobulin G (IgG) and insulin-like growth factor 1 (IGF-1) concentrations, but decreased serum glucose (GLU). Moreover, the mRNA expression of anti-inflammation cytokine (TGF-β), tight junction (Occludin, ZO-1) in the jejunum by different ZnO administration were significantly increased compared with the NC group, while mRNA expression of pro-inflammatory (IL-8), membrane channels that transport water (AQP3) and miR-122a were significantly decreased. It can be concluded that porous ZnO even at low dose (750 mg/kg) can be an effective alternative to pharmacological (3,000 mg/kg) conventional ZnO in reducing diarrhea, promoting the growth performance, increasing anti-inflammatory cytokines and tight junctions, reducing pro-inflammatory cytokines of weaned piglets.

We determined the total energy expenditure (TEE) of healthy overweight or obese people, and those with impaired glucose tolerance and/or impaired fasting glycemia (IGT/IFG), or type 2 diabetes (T2DM) using the doubly-labeled water method. As a second purpose, we compared the measured TEE with the target energy intake recommended in the treatment guidelines for diabetes. The participants were normal glucose tolerance (NGT), and IGT/IFG (n=11) and T2DM (n=9) patients, who were 50-59 y and had a body mass index >25 kg/m². The median TEE/body mass (BM) values were 32.6, 33.3, and 34.4 kcal/kg BM and the TEE/target BM values (target BM: BM at a BMI of 22 kg/m²) were 43.7, 50.2, and 46.5 kcal/kg target BM for each group, respectively, and did not differ significantly among them. Obese Japanese participants with T2DM in this study had lower TEE/BM than previously studied in non-obese participants with T2DM. In IGT/IFG or T2DM patients, if 30 kcal/kg target BM was used as the energy coefficient, on the basis of the treatment guidelines, the difference between TEE and the target energy intake would be −1,174±552 kcal (−38±11%). When 35 kcal/kg target BM was used as the energy coefficient, the difference between TEE and the target energy intake would be −877±542 kcal (−27±13%). Thus, the energy coefficients used to estimate target energy intake during lifestyle modification in obese/overweight patients with T2DM are considered to be quite low during the first step of diet therapy.

In many countries, excessive consumption of sodium chloride (salt) has become a serious social problem and reducing salt has been required. Herbs have been reported to enhance the saltiness of food; however, few studies have focused on the numerical evaluation of the degree of saltiness enhancement by herbs. The purpose of this study was to quantify the degree of saltiness enhancement by herbs via human sensory evaluation using a visual analog scale (VAS). The sensory evaluation was conducted on 69 students who were able to arrange the five different saline concentrations in order. The sensory salt concentration of herb-added 0.4 wt% saline solutions were perceived in comparison with the saltiness of 0.2 to 0.6 wt% reference saline solutions. The results were recorded by an arrow on a VAS. Hot-water extracts of the herbs basil, rosemary, parsley, anise, and oregano were used. The sensory salt concentration of a 0.175 wt% herb-added saline was equivalent to the actual salt concentration (0.4 wt%). However, the sensory salt concentrations of salines with 0.35 wt% herb extracts were significantly higher (p<0.001). There were no significant differences in the saltiness-enhancing effects depending on the species of, preference for, and familiarity with a particular herb. It was estimated that the addition of 0.35 wt% herb extracts enhanced the salty taste of the saline by 1.13 to 1.22 times.

Pectin enhances mucin secretion in the rat small intestine. However, what structural features of pectin to stimulate mucin secretion remain unclear. The study aimed to clarify active constituents of pectin using a human goblet cell line, HT29-MTX. Various pectins at 100 mg/L commonly stimulated MUC5AC secretion, irrespective of their differences in molecular size, plant origin and degree of methoxylation, whereas other dietary fiber materials at 100 mg/L did not show any effects, except fucoidan. Hairy region concentrate (HRC) and its further fractions (F1-F3) were prepared by polygalacturonase treatment of citrus pectin and successive anion exchange chromatography. Neutral sugars, such as galactose and arabinose were enriched in these fractions. HRC and F1-F3 at 30 mg/L significantly increased MUC5AC secretion, which were 3 times more potent compared with a starting material (citrus pectin). Further, a dose-dependent study showed that F1 significantly increased MUC5AC secretion from at 0.3 mg/L, much stronger than that of mucin-secretagogue lipopolysaccharides. Rats consumed 5% apple pectin diet showed significant increases of luminal mucin contents and Muc2 expression in the small intestine, while the luminal mucin contents in rats consumed 1.5% HRC diet were increased by 24% compared to those in rats consumed control diet, but the difference did not reach significant. Thus, HRC is supposed to be active constituents of mucin-secretory effect of pectin in vitro. At present, however, the effect of HRC has not been verified in vivo.

The terrestrial filamentous cyanobacterium, Nostoc commune, has been used as a food source in many countries, especially countries in Asia. In this study, N. commune-derived aqueous extracts were evaluated with regard to their antioxidative and antiglycative properties. The antioxidative activity was significantly higher in N. commune colonies isolated from the field than in extracts from colonies cultured in the laboratory. The antioxidative compound content of extracts, including phenolic compounds and phycobiliproteins, was correlated with their antioxidative power. In addition, two mycosporine-like amino acids (MAAs), specifically detected in colonies isolated from the field, were purified. In addition to assessing their antioxidative properties, the antiglycative activity of these MAAs was also assessed. Their inhibitory effects on glycation-dependent protein cross-linking might contribute to the antiglycative power of the extract prepared from field colonies. Taken together, the results from this study revealed that N. commune may have beneficial properties for functional food applications, both by preventing oxidative stress and suppressing the formation of advanced glycation end-products.

Calorie restriction (CR) by 30-40% decreases morbidity of age-related diseases and prolongs the lifespan of various laboratory animal species. Taurine (2-aminoethanesulfonic acid) is an important nutrient for lipid metabolism as it conjugates bile acids. Here, we investigated how taurine supplementation induces effects similar to the CR beneficial effects. Sprague Dawley rats were fed a diet containing different taurine concentrations (0, 0.5, 1.0, 3.0, 5.0%) to analyze the effects on growth, blood, and hepatic parameters. Rats fed a 5% taurine-supplemented diet showed a significant decrease in visceral fat weight, compared with control rats. Moreover, there were significant decreases in the serum total cholesterol, hepatic cholesterol and triglyceride concentrations in the taurine-supplemented groups compared with the control group in a dose-dependent manner. These results were associated with decreased mRNA expression of fatty acid synthase, and increased mRNA expression of carnitine palmitoyltransferase 1α. C57BL/6 mice were fed a 5.0% taurine-supplemented diet, and their response to 3-nitropropionic acid-induced oxidative stress was analyzed. The rate of weight loss due to oxidative stress decreased and the survival rate significantly increased in the taurine-supplemented groups compared with the control group. Finally, cells were treated with 100 μM taurine and their resistance to UV-induced oxidative stress was analyzed. We found that the p53-Chk1 pathway was less activated in taurine-treated cells compared with control cells. Furthermore, damage to cells evaluated by oxidative stress indicators revealed a reduction in oxidative damage with taurine treatment. These findings suggest that taurine partially acts as a CR mimetic.

Glutathione, the most abundant intracellular antioxidant, protects cells against reactive oxygen species induced oxidative stress and regulates intracellular redox status. We previously demonstrated that yellow Chinese chive (ki-nira) increased the intracellular glutathione levels. Acetaminophen (APAP) is a commonly used analgesic. However, an overdose of APAP causes severe hepatotoxicity via depletion of the hepatic glutathione. In this study, we investigated the hepatoprotective effects of yellow Chinese chive extract (YCE) against APAP-induced hepatotoxicity in mice. YCE (25 or 100 mg/kg) was administered once daily for 7 d, and then APAP (700 mg/kg) was injected at 6 h before the mice were sacrificed. APAP treatment markedly increased the serum biological markers of liver injury such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase. Pretreatment with YCE significantly prevented the increases in the serum levels of these enzymes. Histopathological evaluation of the livers also revealed that YCE prevented APAP-induced centrilobular necrosis. Pretreatment with YCE dose-dependently elevated glutathione levels, but the difference was not significant. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in APAP-induced hepatotoxicity by regulating the antioxidant defense system. Therefore, we investigated the expression of Nrf2 and its target antioxidant enzyme. YCE led to an increased expression of Nrf2 and its target antioxidant enzymes, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (GPx), cystine uptake transporter (xCT), especially hemeoxygenase-1 (HO-1) in mice livers. These results suggest that YCE could induce HO-1 expression via activation of the Nrf2 antioxidant pathway, and protect against APAP-induced hepatotoxicity in mice.

The purpose of this study was to clarify factors affecting the browning of a model processed cheese during storage. Model processed cheese samples (pH 4.5-6.0) which were composed of sugars (galactose, glucose, or lactose; 0-1.8%), amino acids (0-2.8%), sodium caseinate (26.0-31.2%), fat from butter (22.0-28.5%), water (44.1%), emulsifying salts (trisodium citrate, disodium tartrate dihydrate, or disodium hydrogen phosphate; 0 or 1.4%), and salt (0-5.0%) were prepared. Each model processed cheese was stored at 50ºC for 4-7 d. The L*-, a*-, and b*-values of model cheese samples before and after storage were measured and the ΔE-value was calculated to estimate the browning. All model cheese samples turned brown during storage. The ΔE-value strongly correlated with the concentration of galactose (r=0.99), and pH (r=0.94), respectively. The galactose-added model cheese turned more intensively brown than glucose or lactose-added ones. The browning was not dependent on the amount of free amino acids, but on the amount of added sodium caseinate. The browning was repressed by the addition of 1 to 3% of NaCl. The model cheese added with disodium hydrogen phosphate as an emulsifying salt turned more intensively brown than those added with disodium tartrate dihydrate or trisodium citrate. The ΔE-values of model cheese samples containing galactose strongly correlated with the decrease in galactose. These results showed that galactose was one of the most important factors for regulating the browning of processed cheese during storage and that the browning was also dependent on pH, protein, NaCl, and an emulsifying salt.

The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D₃ and also for the secondary bile acid lithocholic acid (LCA). The in vivo role of VDR in bile acid metabolism remains largely uncharacterized. We previously reported that pharmacological VDR activation enhances urinary bile acid excretion, particularly in mice fed chow supplemented with chenodeoxycholic acid (CDCA), which is metabolized to muricholic acid in mouse liver and is also converted to LCA by intestinal bacteria. In this study, we examined the effect of VDR deletion on bile acid composition utilizing VDR-knockout (VDR-KO) mice. VDR deletion did not change total bile acid levels in liver or feces of mice when fed standard chow supplemented with calcium, needed to prevent hypocalcemia in VDR-KO mice. Total bile acid levels in plasma and urine tended to be higher and lower, respectively, in VDR-KO mice. After feeding CDCA-supplemented chow, VDR-KO mice showed decreased hepatic, fecal and urinary total bile acid and CDCA levels compared to wild-type mice. Plasma total bile acids and LCA were relatively high in these mice. These results indicate that VDR deletion influences CDCA metabolism. VDR may play a role in the excretion of excess bile acids.

Effectiveness of retinoic acid (RA) in treating food allergy is not yet clear. Using an allergic mouse model, we examined the amelioration of the severity of food allergy by daily RA intake with allergen or without. Female Balb/c mice were systemically sensitized to egg white (EW) and alum by intraperitoneal injection. Sensitized mice were provided diets supplemented with 0% (non-treated group), 0.1% EW (allergen group), 0.0017% RA (RA group), or 0.1% EW plus 0.0017% RA (RA+allergen group) with 20% casein for 4 wk. Oral food challenge (OFC) and allergic biomarkers were quantified. The decrease in rectal temperature post-OFC was significantly suppressed in the RA and RA+allergen groups compared to those in the non-treated and allergen groups, respectivety. The plasma levels of ovalbumin-specific IgE, IgA and IgG1 at the study endpoint were higher in the allergen and RA+allergen groups than those in the non-treated and RA+allergen groups, respectivety. Plasma ovalbumin-specific IgG2a levels at the study endpoint were significantly higher in the RA+allergen group than those in the RA groups. The supernatant concentrations of interleukin-10 and interferon-γ in the cultured spleen lymphocytes were highest in the RA+allergen group compared to those in the other groups. Thus, continuous intake of RA under allergen exposure ameliorated the severity of food allergy in a mouse model with food allergy.

The purpose of this study was to determine the effect of beta-carotene supplementation to Japanese Black calves on the peripheral blood leukocyte population. Twenty-two Japanese Black calves were alternately assigned to two groups. Eleven calves received 20 mg/d of beta-carotene orally from 2 to 8 wk of age (BC group), and the other 11 calves did not receive (control group). The serum beta-carotene concentration in the BC group at 4, 8 and 12 wk of age were significantly higher than those in the control group (p<0.05). The numbers of CD4⁺ cells in the BC group were significantly higher than those in the control group at 4 wk of age (p<0.05). These results confirmed that beta-carotene supplementation to Japanese Black calves affected the peripheral blood leukocyte population.

We aimed to examine the correlations between vitamin D deficiency, severity of dry eye symptoms and primary Sjögren’s syndrome (pSS) by performing a systematic review and meta-analysis. Online databases (PubMed, Cochrane Library, and Embase) were searched to identify controlled studies comparing (1) severity of dry eye symptoms between participants with and without vitamin D deficiency; and (2) serum vitamin D levels between patients with and without pSS. Eighteen studies were included. Overall, individuals with vitamin D deficiency had shorter tear breakup time (TBUT), lower Schirmer’s test scores and higher ocular surface disease index (OSDI) score than those without vitamin D deficiency. Additionally, serum vitamin D levels were found to be lower in pSS than controls. Our findings highlight the importance of vitamin D deficiency in the severity of dry eye symptoms and pSS.