BACKGROUND/OBJECTIVES: Folate plays a critical role in DNA synthesis and methylation. Intracellular folate homeostasis is maintained by the enzymes folylpolyglutamate synthase (FPGS) and γ-glutamyl hydrolase (GGH). FPGS adds glutamate residues to folate upon its entry into the cell through a process known as polyglutamylation to enhance folate retention in the cell and to maintain a steady supply of utilizable folate derivatives for folate-dependent enzyme reactions. Thereafter, GGH catalyzes the hydrolysis of polyglutamylated folate into monoglutamylated folate, which can subsequently be exported from the cell. The objective of this review is to summarize the scientific evidence available on the effects of intracellular folate homeostasis-associated enzymes on cancer chemotherapy. METHODS: This review discusses the effects of FPGS and GGH on chemosensitivity to cancer chemotherapeutic agents such as antifolates, such as methotrexate, and 5-fluorouracil. RESULTS AND DISCUSSION: Polyglutamylated (anti)folates are better substrates for intracellular folate-dependent enzymes and retained for longer within cells. In addition to polyglutamylation of (anti)folates, FPGS and GGH modulate intracellular folate concentrations, which are an important determinant of chemosensitivity of cancer cells toward chemotherapeutic agents. Therefore, FPGS and GGH affect chemosensitivity to antifolates and 5-fluorouracil by altering intracellular retention status of antifolates and folate cofactors such as 5,10-methylenetetrahydrofolate, subsequently influencing the cytotoxic effects of 5-fluorouracil, respectively. Generally, high FPGS and/or low GGH activity is associated with increased chemosensitivity of cancer cells to methotrexate and 5-fluorouracil, while low FPGS and/or high GGH activity seems to correspond to resistance to these drugs. Further preclinical and clinical studies elucidating the pharmocogenetic ramifications of these enzyme-induced changes are warranted to provide a framework for developing rational, effective, safe, and customized chemotherapeutic practices.

BACKGROUND/OBJECTIVES: In Oriental medicine, certain foods may be beneficial or detrimental based on an individual's constitution; however, the scientific basis for this theory is insufficient. The purpose of this study was to investigate the effect of body constitution, based on the Sasang type of Korean traditional medical classification system, on the bioavailability of soy isoflavones of Cheonggukjang, a quick-fermented soybean paste. SUBJECTS/METHODS: A pilot study was conducted on 48 healthy Korean men to evaluate the bioavailability of isoflavone after ingestion of food based on constitution types classified by the Sasang typology. The participants were classified into the Taeeumin (TE; n = 15), Soyangin (SY; n = 15), and Soeumin (SE; n = 18) groups. Each participant ingested 50 g of Cheonggukjang per 60 kg body weight. Thereafter, blood was collected, and the soy isoflavone metabolites were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Ntrikinetic analysis of individual isoflavone-derived metabolites was performed. RESULTS: Our nutrikinetic analysis identified 21 metabolites derived from isoflavones in the blood samples from 48 healthy Korean men (age range, 21-29 years). Significant differences were observed in the time to maximum concentration (T_max) and elimination half-life (t_1/2) for nine metabolites among the three groups. The T_max and t_1/2 of the nine metabolites were higher in the SE group than in the other groups. Moreover, the absorption rates, as determined by the area under the plasma-level curve (AUC) values of intact isoflavone, were 5.3 and 9.4 times higher in the TE group than in the SY and SE groups, respectively. Additionally, the highest AUC values for phase I and II metabolites were observed in the TE group. CONCLUSIONS: These findings indicate that isoflavone bioavailability, following Cheonggukjang insgestion, is high in individuals with the TE constitution, and relatively lower in those with the SE and SY constitutions.

BACKGROUND/OBJECTIVES: Excessive intake of simple sugars induces obesity and increases the risk of inflammation. Thus, interest in alternative sweeteners as a sugar substitute is increasing. The purpose of this study was to determine the effect of saccharin on inflammation in 3T3-L1 adipocytes. MATERIALS/METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes. The adipocytes were treated with saccharin (0, 50, 100, and 200 ㎍/mL) for 24 h. Inflammation was induced by exposure of treated adipocytes to lipopolysaccharide (LPS) for 18 h and cell proliferation was measured. The concentration of nitric oxide (NO) was measured by using Griess reagent. Protein expressions of nuclear factor kappa B (NF-κB) and inhibitor κB (IκB) were determined by western blot analysis. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were determined by real-time PCR. RESULTS: Compared with the control group, the amount of NO and the mRNA expression of iNOS in the LPS-treated group were increased by about 17.6% and 46.9%, respectively, (P < 0.05), and those parameter levels were significantly decreased by saccharin treatment (P < 0.05). Protein expression of NF-κB was decreased and that of IκB was increased by saccharin treatment (P < 0.05). Saccharin decreased the mRNA expression of COX-2 and the inflammation cytokines (IL-1β, IL-6, MCP-1, and TNF-α) (P < 0.05). CONCLUSIONS: The results of this study suggest that saccharin can inhibit LPS-induced inflammatory responses in 3T3-L1 adipocytes via the NF-κB pathway.

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months. SUBJECTS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6-12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections). RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D. CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells. MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action. RESULTS: Administration with up to 40 μM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 μM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels. CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

BACKGROUND/OBJECTIVES: North Korean refugees (NKRs) in South Korea are a unique population as they must adapt in a new country with similar cultural traits but different social, political, and economic systems, but little research has been conducted on diet and nutrition in this population. This study examined food security, dietary behaviors, and nutrient intakes among adult NKRs living in South Korea and compared them to those of South Koreans. SUBJECTS/METHODS: The subjects were 139 adult NKRs (25 men, 114 women) living in the Seoul metropolitan area, and 417 age- and sex- matched South Korean controls (SKCs; 75 men, 342 women) selected from the Korea National Health and Nutrition Examination Survey (KNHANES). Food security and dietary behaviors (meal skipping, eating-out, meals with family, nutrition education and counseling, and nutrition label knowledge and utilization) were obtained using self-administered questionnaires. Nutrient intakes were assessed by 24-hr recall. The statistical analysis was performed using IBM SPSS ver. 23.0. RESULTS: In South Korea, food security had improved over the previous 12 months, but remained significantly poorer for NKR women than SKC women. Meal skipping was three times more frequent than for SKCs and eating-out was rare. Average energy intake was 1,509 kcal for NKR men and 1,344 kcal for NKR women, which was lower than those of SKCs (2,412 kcal and 1,789 kcal, respectively). Significantly more NKRs (men 24.0%, women 21.9%) showed simultaneously deficient intake in energy, calcium, iron, vitamin A, and riboflavin than SKCs (men 2.7% (P = 0.003), women 7.0% (P < 0.001)). NKR women had a significantly higher index of nutrient quality (INQ) for some nutrients than SK women. CONCLUSIONS: This study reports significant differences in food security, dietary behaviors, and nutrient intakes between NKRs and SKCs. Generally, NKRs reported lower intakes despite improved food security, but relatively good INQs across nutrients. Further research is needed to understand processes of food choice and consumption among NKRs to provide appropriate support aimed at improving diets.

BACKGROUND/OBJECTIVES: The nutrition of the elderly depends on various factors. Oral health, especially oral dryness, can be an important risk factor. In this study, we attempted to determine whether dry mouth is associated with compromised nutrient intakes. SUBJECTS/METHODS: A total of 120 participants aged 65-86 yrs (mean age: 69 ± 1 y) were included in this study. Demographic and health-related characteristics, living status, meals, number of medications, medical conditions, chewing ability, and quality of life, the Oral Health Impact Profile (the OHIP-14) were assessed. We performed one day 24-hr recall assessment for nutrient analyses. The differences of the means between the dry-mouth and non-dry-mouth groups were analyzed. Elderly subjects with xerostomia-induced dry mouth were classified as those who reported at least one dryness symptom on a questionnaire. RESULTS: A significant difference in population distribution was observed among the elderly who took medications for hypertension, diabetes and osteoporosis and was significantly higher in the dry-mouth group (70.2%) than in the non-dry-mouth group (44.4%) (P = 0.005). Compared with the non-dry-mouth group (50.8%), a significantly higher proportion (73.7%) of participants in the dry-mouth group took multiple medicines (≥ 4 medications) (P = 0.019). The intakes of vegetable fat, vitamin E, folate and water in the dry-mouth group were lower than in the non-dry-mouth group. The intakes of fluoride and ω-3 fatty acids were significantly lower in the dry-mouth group than in the non-dry-mouth group. CONCLUSION: The participants in the dry-mouth group exhibited low nutrient and water intakes. It is recommended that the elderly with dry mouth should drink sufficient water and receive targeted and specific nutritional guidance to prevent malnutrition.

BACKGROUND/OBJECTIVES: Hypertriglyceridemia may be a more important predictor of cardiovascular disease in Asian population consuming carbohydrate-rich foods than in Western populations. Dairy products are known to play a beneficial role in obesity, dyslipidemia, and metabolic syndrome, but the results vary depending on gender and obesity. In this study, we investigated the associations between dairy product intake and hypertriglyceridemia in Korean adults. SUBJECTS/METHODS: The participants were selected from the Korea National Health and Nutrition Examination Survey 2007-2012 (KNHANES IV and V). A total of 22,836 participants aged 19-64 years were included in the analysis. A food frequency questionnaire used to determine the frequency of consumption of products (milk and yogurt). Multivariable logistic regression was used to assess the associations between dairy product intake and hypertriglyceridemia. RESULTS: A significantly decreased risk of hypertriglyceridemia was detected in the highest dairy product intake frequency group (≥ 1 time/day) (odd ratio [OR] = 0.79; 95% confidence interval [CI] 0.64-0.97, P for trend = 0.022) compared to that for the lowest dairy product intake frequency group. Among obese participants, the group with the highest intakes of milk (in men, OR = 0.64; 95% CI: 0.46-0.91, P for trend = 0.036) and yogurt (in women; OR = 0.53; 95% CI: 0.29-0.94, P for trend = 0.019) showed inverse associations with hypertriglyceridemia. No associations were detected in normal weight participants. CONCLUSION: The association between dairy product intake and hypertriglyceridemia differed by gender and obesity status. Further prospective studies are needed to confirm these associations.

BACKGROUND/OBJECTIVES: The obese population is rapidly increasing because of reduced physical activity and a Westernized diet; consequently, various chronic diseases are more prevalent. With the increasing interest in body shape and appearance, research on body shape perceptions and accompanying weight control behaviors are needed for healthy weight management. SUBJECTS/METHODS: A cross-sectional survey was conducted on randomly selected 536 (209 men and 327 women) aged 20 to 65 years. Body mass index (BMI), body-shape perception, weight control behavior, quality of sleep, and place of residence were collected using self-reported questionnaires. Multivariable logistic regression analysis was conducted using complex design in each groups. Collected data were analyzed using the SAS 9.4 statistical package, and the significance level was set at P < 0.05. RESULTS: When these two variables were divided into four groups, they were found to influence dieting attempts. People with abnormal weights who were dissatisfied with their body shapes attempted dieting 5.23 times more than those with healthy weights and satisfaction with their body shapes. Further, those with normal weights but dissatisfaction with their bodies attempted dieting 4.45 times more than those who were satisfied with their shapes. Subjects in their 20s attempted dieting 2.53 times more than those in their 30s and 40s, and female subjects attempted dieting 2.24 times more than male subjects. CONCLUSIONS: A correct perception of one's shape can be an important factor for dietary behavior, as body shape perceptions and dieting attempts are strongly related. Additionally, healthy weight management and nutrition education are important elements to incorporate into a weight control program aimed at preventing excessive weight control behaviors and promoting correct perceptions of body shape.

BACKGROUND/OBJECTIVES: With the advances in technologies, self-service kiosks at foodservice operations are becoming a new way of service provision. This study examined the relationships among the menu information quality, nutrition information quality, technology acceptance characteristics, and customer behavioral intention toward the kiosks in fast food restaurants. SUBJECTS/METHODS: A survey with a self-administered method was distributed online and offline. The sample consisted of customers who had used the kiosks at fast food restaurants in the last six months prior to the survey. The study hypotheses were tested by applying structural equation modeling. RESULTS: Structural equation modeling revealed the positive impacts of menu information quality and nutrition information quality, technology acceptance characteristics, and behavioral intention toward kiosks at fast food restaurants. On the other hand, one hypothesis (Hypothesis 4) on the impact of nutrition information quality on the perceived usefulness was rejected. CONCLUSION: The study is the first to investigate nutrition and menu information at foodservice kiosks and relate them to technology acceptance. The study is very timely and adequate in the time of the 4^th industrial revolution. The critical importance of the presentation of nutrition information and menu information at the kiosks at fast food restaurants was verified. The academic and industrial implications of the study findings were discussed.