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1.  Evaluation of Adiposity-Related Biomarkers as Metabolic Syndrome Indicators 
Clinical Nutrition Research  2013;2(2):91-99.
Recent studies have suggested a relationship of the increased circulating adipokines and inflammatory cytokine, and the risk of metabolic syndrome (MetS). The objective of this study was to identify adiposity-related factors that reflect MetS in order to establish early intervention targets. We performed a cross-sectional study which included 108 MetS subjects and 91 controls. Blood adiponectin, leptin, vascular-, and intercellular adhension molecules (VCAM, ICAM), monocyte chemoattractant protein 1 (MCP1), high-sensitivity C-reactive protein (hsCRP), oxidized LDL (oxLDL), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured. The correlation analysis indicated that the MetS score (sum of the number of MetS risk factors) had an inverse relationship with adiponectin (p < 0.0001), and positive correlations with leptin (p < 0.05), ICAM (p < 0.01), MCP1 (p < 0.05), oxLDL (p < 0.05), TNF-α (p < 0.0001), IL-6 (p < 0.05) and hsCRP (p < 0.01). In multivariate logistic regression analyses, plasma triglyceride (TG) was independently associated with adiponectin, ICAM and TNF-α with the standardized β coefficients of -0.213, 0.197, and 0.193, respectively. Plasma HDL-cholesterol was independently associated with ICAM and hsCRP with the standardized β coefficients of -0.150 and -0.173. Adiponectin, TNF-α, and hsCRP were the most proximate markers reflecting MetS. Among MetS components, TG and HDL-cholesterol concentrations displayed the relationship with inflammatory markers measured in this study.
PMCID: PMC3728468  PMID: 23908975
Metabolic syndrome; Adiposity; Adipokines; Inflammatory cytokines; Abdominal fat
2.  Modulatory effects of α- and γ-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells 
Nutrition Research and Practice  2009;3(3):185-191.
The elevated level of circulating estradiol increases the risk of breast tumor development. To gain further insight into mechanisms involved in their actions, we investigated the molecular mechanisms of 4-hydroxyestradiol (4-OHE2) to initiate and/or promote abnormal cell growth, and of α- or γ-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with 0.1 µM 4-OHE2, either with or without 30 µM tocopherols for 96 h. 4-OHE2 caused the accumulation of intracellular ROS, while cellular GSH/GSSG ratio and MnSOD protein levels were decreased, indicating that there was an oxidative burden. 4-OHE2 treatment also changed the levels of DNA repair proteins, BRCA1 and PARP-1. γ-Tocopherol suppressed the 4-OHE2-induced increases in ROS, GSH/GSSG ratio, and MnSOD protein expression, while α-tocopherol up-regulated BRCA1 and PARP-1 protein expression. In conclusion, 4-OHE2 increases oxidative stress reducing the level of proteins related to DNA repair. Tocopherols suppressed oxidative stress by scavenging ROS or up-regulating DNA repair elements.
PMCID: PMC2808717  PMID: 20090883
Breast cancer; DNA damage; 4-hydroxyestradiol; oxidative stress; tocopherol
3.  Involvement of Transglutaminase-2 in α-MSH-Induced Melanogenesis in SK-MEL-2 Human Melanoma Cells 
Biomolecules & Therapeutics  2014;22(3):207-212.
Skin hyperpigmentation is one of the most common skin disorders caused by abnormal melanogenesis. The mechanism and key factors at play are not fully understood. Previous reports have indicated that cystamine (CTM) inhibits melanin synthesis, though its molecular mechanism in melanogenesis remains unclear. In the present study, we investigated the effect of CTM on melanin production using ELISA reader and the expression of proteins involved in melanogenesis by Western blotting, and examined the involvement of transglutaminase-2 (Tgase-2) in SK-MEL-2 human melanoma cells by gene silencing. In the results, CTM dose-dependently suppressed melanin production and dendrite extension in α-MSH-induced melanogenesis of SK-MEL-2 human melanoma cells. CTM also suppressed α-MSH-induced chemotactic migration as well as the expressions of melanogenesis factors TRP-1, TRP-2 and MITF in α-MSH-treated SK-MEL-2 cells. Meanwhile, gene silencing of Tgase-2 suppressed dendrite extension and the expressions of TRP-1 and TRP-2 in α-MSH-treated SK-MEL-2 cells. Overall, these findings suggested that CTM suppresses α-MSH-induced melanogenesis via Tgase-2 inhibition and that therefore, Tgase-2 might be a new target in hyperpigmentation disorder therapy.
PMCID: PMC4060083  PMID: 25009701
Cystamine; Melanogenesis; Transglutaminase-2; TRP-1; TRP-2; SK-MEL-2 melanoma cells
4.  Validity and reproducibility of a food frequency questionnaire to assess dietary nutrients for prevention and management of metabolic syndrome in Korea 
Nutrition Research and Practice  2010;4(2):121-127.
Little data exists on metabolic syndrome (MetS) related with intake, especially for the South Korean. The purpose of this study was to develop and evaluate a food frequency questionnaire (FFQ) for nutritional assessment in the population with MetS in South Korea. Randomly selected female participants, mean age 21.9 years (n = 38) were invited to answer the FFQ twice (FFQ1 and FFQ2) over a nine-month interval and to complete twelve-day diet records (DR) during the months between in South Korea. The correlation coefficients for nutrient intake between FFQ1 and FFQ2 varied from 0.253 (niacin) to 0.573 (cholesterol), and the energy intake-adjusted correlation coefficients ranged from 0.187 for protein to 0.662 for iron. The energy intake-adjusted and de-attenuated correlation coefficients for comparison of FFQ1 and the DRs ranged between 0.277 (vitamin B1) and 0.768 (fiber), and between 0.229 (zinc) and 0.859 (fat) for comparison of DRs with FFQ2. The percentages of study subjects classified into the same quartiles in both the DRs and FFQ1 ranged from 15.8% (vitamin B6) to 47.4% (calcium), and for the same quartiles in DRs and FFQ2 from 13.2% (vitamin B1) to 44.7% (potassium). The FFQ has reasonably good validity and reproducibility. Further research is needed for an assessment of reproducibility and validation of present FFQ in the subjects with MetS.
PMCID: PMC2867222  PMID: 20461200
Metabolic syndrome; food frequency questionnaire; Korean adults; validity; reproducibility
5.  The relationship of dietary sodium, potassium, fruits, and vegetables intake with blood pressure among Korean adults aged 40 and older 
Nutrition Research and Practice  2014;8(4):453-462.
The inverse relationships of combined fruits and vegetables intake with blood pressure have been reported. However, whether there are such relationships with salty vegetables has rarely been investigated in epidemiologic studies. We evaluated the relation of combined and separate intake of fruits, vegetable intakes, and salty vegetables, as well as sodium and potassium, with blood pressure among the middle-aged and elderly populations.
The present cross-sectional analysis of a prospective cohort baseline survey was performed with 6,283 subjects (2,443 men and 3,840 women) and free of hypertension, diabetes, cardiovascular diseases, and cancer. Dietary data were collected by trained interviewers using food frequency questionnaire.
The significantly inverse linear trend of diastolic blood pressure (DBP) was found in fruits and non-pickled vegetables (81.2 mmHg in the lowest quintile vs 79.0 mmHg in the highest quintile, P for trend = 0.0040) and fruits only (80.9 mmHg in the lowest quintile vs 79.4 mmHg in the highest quintile, P for trend = 0.0430) among men. In contrast, sodium and sodium to potassium ratio were positively related with blood pressure among men (DBP, 78.8 mmHg in the lowest quintile vs 80.6 mmHg in the highest quintile, P for trend = 0.0079 for sodium; DBP, 79.0 mmHg in the lowest quintile vs 80.7 mmHg in the highest quintile, P for trend = 0.0199 and SBP, 123.8 mmHg in the lowest quintile vs 125.9 mmHg in the highest quintile for sodium/potassium). Kimchies consumption was positively related to DBP for men (78.2 mmHg in the lowest quintile vs 80.9 mmHg in the highest quintile for DBP, P for trend = 0.0003). Among women, these relations were not found.
Fruits and/or non-pickled vegetables may be inversely, but sodium, sodium to potassium, and Kimchies may be positively related to blood pressure among men.
PMCID: PMC4122719  PMID: 25110567
Sodium; potassium; fruits and vegetables; Kimchies; blood pressure
6.  Expression Profiles of Epithelial-Mesenchymal Transition-Associated Proteins in Epithelial Ovarian Carcinoma 
BioMed Research International  2014;2014:495754.
Epithelial-mesenchymal transition (EMT) has been suggested to contribute to tumor progression and acquisition of therapeutic resistance. To assess the clinical significance of EMT-associated proteins, we evaluated the expression of Snail and Slug, the key regulators of EMT, in the primary ovarian cancer samples (n = 103) by immunohistochemistry. Snail was differentially expressed according to the histologic subtype (P = 0.001) and was predominantly expressed in serous and endometrioid types. In the serous and endometrioid adenocarcinomas, the expression of Snail remained high across the stage and grade, suggesting its role in the early phase of carcinogenesis. However, the expression of Snail and Slug was not related to chemoresistance and poor prognosis and did not serve as independent predictive or prognostic marker.
PMCID: PMC3988710  PMID: 24800235
7.  Assessment of the Association between Mean Hemoglobin A1c Levels for 5 Years and Coronary Artery Disease by Coronary Angiography in Nondiabetic Patients 
Diabetes & Metabolism Journal  2014;38(1):58-63.
The effects of glucose on cardiovascular events or mortality in nondiabetic patients has been recently reported. However, since atherosclerosis can be formed over a long period of time, it is necessary to devote several years to unveil the relationship between the two factors. Here, we attempted to find out the relationship between the mean hemoglobin A1c (HbA1c) level and HbA1c variability for 5 years and coronary artery disease (CAD) by using coronary angiography (CAG) to assess nondiabetic patients.
We reviewed patients who performed CAG who were followed up for at least 5 years after the initial diagnosis. The fasting blood test was performed annually for glucose and HbA1c level. CAD was defined as more than 50% of luminal narrowing. The severity of CAD was divided into two groups depending on whether no vessels were involved or one more vessel were involved (CAD(-) or CAD(+), respectively).
The patients in CAD(+) group had higher mean HbA1c level for 5 years than CAD(-) group (5.71±0.40 vs. 5.86±0.68; P=0.04). Mean HbA1c was a significant predictor for CAD in multiple regression (odds ratio, 2.224; P=0.028). The percentage of patients with CAD was significantly higher in patients with >6.2% of mean HbA1c levels compared to patients with <6.2% of mean HbA1c levels (P<0.019).
When the mean HbA1c levels were above 6.2%, the risk of CAD was higher. Also this study shows that HbA1c level can be one of the predictors for CAD even if the patients do not have diabetes.
PMCID: PMC3950196  PMID: 24627829
Coronary artery disease; Hemoglobin A, glycosylated
9.  Maternal and grandmaternal obesity and environmental factors as determinants of daughter's obesity 
Nutrition Research and Practice  2013;7(5):400-408.
Obesity may be the consequence of various environmental or genetic factors, which may be highly correlated with each other. We aimed to examine whether grandmaternal and maternal obesity and environmental risk factors are related to obesity in daughters. Daughters (n = 182) recruited from female students, their mothers (n = 147) and their grandmothers (n = 67) were included in this study. Multivariable logistic regression was used to analyze the association between the daughter's obesity and maternal, grandmaternal, and environmental factors. Maternal heights of 161-175cm (OD: 8.48, 95% CI: 3.61-19.93) and 156-160 cm (2.37, 1.14-4.91) showed positive associations with a higher height of daughter, compared to those of 149-155 cm. Mothers receiving a university or a higher education had a significant OR (3.82, 1.27-11.50) for a higher height of daughter compared to those having a low education (elementary school). Mother having the heaviest weight at current time (59-80 kg, 3.78, 1.73-8.28) and the heaviest weight at 20 years of age (51-65 kg, 3.17, 1.53-6.55) had significant associations with a higher height of daughters, compared to those having the lightest weight at the same times. There was no association between the height, weight, and BMI of daughters and the characteristics and education of her grandmothers. In conclusion, although genetic factors appear to influence the daughter's height more than environmental factors, the daughter's weight appears to be more strongly associated with individual factors than the genetic factors.
PMCID: PMC3796666  PMID: 24133620
Trans generational; body mass index; daughter; mother; grandmother
10.  Dietary Supplements Use and Related Factors of Preschoolers in 3 Korean Cities 
To estimate the prevalence of dietary supplement (DS) use, investigate the related factors associated with DS use among preschoolers and support the adequate nutrition.
We conducted a questionnaire survey of mothers of children aged between 1 and 6 years who visited pediatric clinics in 3 Korean cities (Jeonju, Suncheon, Jeongeup) between October and November 2012 at Presbyterian Medical Center. The responses from 929 questionnaires were analyzed.
Approximately 45.1% of the preschoolers used DS in the past month. The following factors were associated with greater use of DS: older age (p<0.001), whether or not the preschoolers attended kindergarten (p<0.001), higher mother's concern about the nutritional facts (p<0.001), whether or not the mother use DS (p<0.001), whether or not the mother counsel with a doctor or pharmacist about DS use (p<0.001). Vitamin·mineral supplements (77.5%) were the most commonly used DS among the preschoolers, followed by ginseng (49.3%) and probiotics (25.6%). Additionally, of the DS users, 95.9% gave DS to their healthy children. Of the users and non-users, 97.6% and 62.2%, respectively, indicated that they would like to have their children take DS. The information on DS was obtained from family or friends in 48.2% of the DS users and from doctors in only 6.1%.
Approximately half of the preschoolers in our study used DS, which might not have been medically indicated for most of them. Therefore, the role of professionals in counseling on desirable diet behaviors and DS use for preschoolers is warranted.
PMCID: PMC3760705  PMID: 24010114
Dietary supplements; Preschool; Energy intake
11.  A1c Variability Can Predict Coronary Artery Disease in Patients with Type 2 Diabetes with Mean A1c Levels Greater than 7 
Endocrinology and Metabolism  2013;28(2):125-132.
Recent studies suggested that the association of acute glucose variability and diabetic complications was not consistent, and that A1c variability representing long term glucose fluctuation may be related to coronary atherosclerosis in patients with type 1 diabetes. In this study, we attempt to determine whether or not A1c variability can predict coronary artery disease (CAD) in patients with type 2 diabetes.
We reviewed data of patients with type 2 diabetes who had undergone coronary angiography (CAG) and had been followed up with for 5 years. The intrapersonal standard deviation (SD) of serially-measured A1c levels adjusted by the different number of assessments among patients (adj-A1c-SD) was considered to be a measure of the variability of A1c.
Among the 269 patients, 121 of them had type 2 diabetes with CAD. In patients with A1c ≥7%, the mean A1c levels and A1c levels at the time of CAG among the three groups were significantly different. The ratio of patients with CAD was the highest in the high adj-A1c-SD group and the lowest in the low adj-A1c-SD group (P=0.017). In multiple regression analysis, adj-A1c-SD was an independent predictor for CAD in subjects with A1c ≥7% (odds ratio, 2.140; P=0.036).
Patients with higher A1c variability for several years showed higher mean A1c levels. A1c variability can be an independent predictor for CAD as seen in angiographs of patients with type 2 diabetes with mean A1c levels over 7%.
PMCID: PMC3811710  PMID: 24396666
A1c variability; Coronary artery disease; Diabetes mellitus, type 2
12.  Development of a Korean Diet Score (KDS) and its application assessing adherence to Korean healthy diet based on the Korean Food Guide Wheels 
The most critical point in the assessment of adherence to dietary guidelines is the development of a practical definition for adherence, such as a dietary pattern score. The purpose of this study was to develop the Korean Diet Score (KDS) based on the Korean Food Balance Wheel and to examine the association of KDS with various lifestyle characteristics and biochemical factors. The dietary data of 5,320 subjects from the 4th Korean National Health and Nutritional Examination Survey were used for the final analysis. The food guide was composed of six food group categories; 'grain dishes', 'fish and meat dishes', 'vegetable dishes', 'fruits', 'milk' and 'oils and sugars'. Based on the recommended serving numbers for each group, the scores measuring adherence to this food guide were calculated from the dietary information from the 24-hour dietary recall questionnaire, and then its correlation with various characteristics was assessed. KDS was significantly associated with several clinical, lifestyle and socioeconomic factors as well as diagnosed disease history. The higher quintile group of KDS showed a significantly lower level in fasting blood glucose, systolic blood pressure, triglycerides, current smoking and drinking as well as higher leisure time activity, house income and education. Furthermore, the KDS quintile group of women was inversely associated with hypertension, osteoporosis and diabetes. A higher KDS quintile was characterized with a higher intake of several critical nutrients, such as Ca, Fe and vitamins as well as a desirable nutrition balance such as the ratio of macronutrients. Our results demonstrate that KDS is a beneficial tool in assessing the adherence to a healthy diet based on the Korean dietary guidelines. We suggest that KDS could be a useful indicator for evaluating the dietary balance of the Korean population.
PMCID: PMC3572226  PMID: 23424060
KDS; KNHANES; dietary guidelines; dietary patterns; Korea
13.  Educational attainment and differences in fruit and vegetable consumption among middle-aged adults in the Korean National Health and Nutrition Examination Survey IV 
Nutrition Research and Practice  2012;6(3):263-269.
We investigated whether socioeconomic differences affect fruit and vegetable (FV) consumption with respect to total intake and intake of various FV subgroups. Our study included 6667 adults aged 40-64 years who completed a dietary survey in the fourth Korean NHANES (2007-2009). FV intake was estimated from 24-hour recalls and food frequency questionnaires. Differences in FV consumption related to educational attainment were analyzed according to different nutritional categories of FV. Both men and women in the low-education group had the lowest intake of total FV and total fruits, and women also had the lowest intake of total vegetables. Also lowest in this group was consumption of mushrooms and vegetables (excluding kimchi) among men, and cruciferous and allium vegetables (excluding Chinese cabbage and radish) among women, while kimchi consumption was the highest in this group. Additionally, an association between educational level and intake of citrus fruits was evident among men. Adults in the low-education group consumed less carotene-rich FV, red fruit and/or vegetables, and dark-green leafy vegetables, fewer total vegetable dishes, and fewer types of fruit than in other groups. Men in this group had the lowest intake of yellow/orange fruit and/or vegetables, and women consumed the least folate-rich FV. There is a clear association between educational attainment and FV intake with regard to total intake, and to specific nutrients, bioactive compounds, colors, and variety.
PMCID: PMC3395793  PMID: 22808352
Fruit and vegetables (FV); educational level
14.  The effect of a healthy school tuck shop program on the access of students to healthy foods 
Nutrition Research and Practice  2012;6(2):138-145.
The objective of this study was to evaluate the effect of a healthy school tuck shop program, developed as a way of creating a healthy and nutritional school environment, on students' access to healthy foods. Five middle schools and four high schools (775 students) participated in the healthy school tuck shop program, and nine schools (1,282 students) were selected as the control group. The intervention program included restriction of unhealthy foods sold in tuck shops, provision of various fruits, and indirect nutritional education with promotion of healthy food products. The program evaluation involved the examination of students' purchase and intake patterns of healthy foods, satisfaction with the available foodstuffs, and utilization of and satisfaction with nutritional educational resources. Our results indicated that among of the students who utilized the tuck shop, about 40% purchased fruit products, showing that availability of healthy foods in the tuck shop increased the accessibility of healthy foods for students. Overall food purchase and intake patterns did not significantly change during the intervention period. However, students from the intervention schools reported higher satisfaction with the healthy food products sold in the tuck shop than did those from the control schools (all P < 0.001), and they were highly satisfied with the educational resources provided to them. In conclusion, the healthy school tuck shop program had a positive effect on the accessibility of healthy food. The findings suggest that a healthy school tuck shop may be an effective environmental strategy for promoting students' access to healthy foods.
PMCID: PMC3349036  PMID: 22586503
School tuck shop; healthy eating; intervention program; fruits and vegetables
15.  Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review 
Experimental Diabetes Research  2012;2012:509437.
Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis.
PMCID: PMC3303544  PMID: 22474424
16.  Relative validities of 3-day food records and the food frequency questionnaire 
Nutrition Research and Practice  2010;4(2):142-148.
The food frequency questionnaire (FFQ) has been used as an important dietary assessment tool in epidemiologic studies, but the usefulness of the FFQ has been debated in recent years. This study was performed to evaluate the relative validities of 3-day food records and the semi-quantitative FFQ. A total of 124 subjects finished 3-day food records (FRs) during each of the four seasons, as well as the FFQ from December 2002 to May 2004. The FFQ was a food based semi-quantitative FFQ including 103 items. Three-day FRs from each season and a randomly selected season were compared with the remaining 9-day FRs. The remaining 9-day FRs, as a reference measurement, were also compared with the FFQ. Pearson's correlation coefficients between the 3-day FRs and the 9-day FRs were between 0.14 and 0.56. Pearson's correlation coefficients between the FFQ and the 9-day FRs ranged between 0.07 and 0.41. Average proportions of classification into the same quartiles, adjacent quartiles, and distant quartiles between the 3-day FRs and the 9-day FRs were 35.8%, 40.5%, and 5.2%, respectively. On average, the proportions of classification into the same quartiles, adjacent quartiles, and distant quartiles between the FFQ and the 9-day FRs were 31.1%, 39.4%, and 6.9%, respectively. Three-day FRs showed higher correlations and higher agreement proportions of quartile classification with the 9-day FRs than did the FFQ, but both relative validities of 3-day FRs and the FFQ appear to be acceptable as dietary assessment tools. Further studies for validating food intake by reliable biomarkers are necessary.
PMCID: PMC2867225  PMID: 20461203
Relative validity; food records; food frequency questionnaire
17.  Effect of corn gluten and its hydrolysate consumptions on weight reduction in rats fed a high-fat diet 
Nutrition Research and Practice  2009;3(3):200-207.
This study examined the effects of corn gluten (CG) and its hydrolysate consumptions on weight reduction in rats fed a high-fat diet. Eight-month-old male Sprague-Dawley rats (n=40) were fed a high-fat diet (40% calorie as fat) for 4 weeks. They were then randomly divided into four groups and fed the isocaloric diets with different protein sources for 8 weeks. The protein sources were casein (control group), intact CG (CG group), CG hydrolysate A (CGHA group, 30% of protein as peptides and 70% as free amino acids) and CG hydrolysate P (CGHP group, 93% of protein as peptides and 7% as free amino acids). Body weight gain, adipose tissue weights, nitrogen balance, absorptions of energy, protein and fat, lipid profiles in plasma, liver and feces and hepatic activities of carnitine palmitoyl transferase (CPT), fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PDH) were assessed. The CGHA diet had the highest amount of BCAAs, especially leucine, and most of them existed as free amino acid forms. The CGHA group showed significant weight reduction and negative nitrogen balance. Protein absorption and apparent protein digestibility in the CGHA group were significantly lower than those in other groups. Adipose tissue weights were the lowest in the CGHA group. Activity of CPT tended to be higher in the CGHA group than in other groups and those of FAS, ME and G6PDH were significantly lower in the CGHA group than in other groups. In conclusion, the CGHA diet which had relatively high amounts of free amino acids and BCAAs, especially leucine, had a weight reduction effect by lowering adipose tissue weight and the activities of FAS, ME and G6PDH in experimental animals, but it seemed to be a negative result induced by lowering protein absorption, increasing urinary nitrogen excretion and protein catabolism.
PMCID: PMC2808719  PMID: 20090885
Corn gluten hydrolysate; weight reduction; dietary free amino acids; BCAAs; leucine
18.  Effect of Chlorella vulgaris intake on cadmium detoxification in rats fed cadmium 
The aim of this study was to investigate if dietary Chlorella vulgaris (chlorella) intake would be effective on cadmium (Cd) detoxification in rats fed dietary Cd. Fourteen-week old male Sprague-Dawley (SD) rats weighing 415.0 ± 1.6 g were randomly divided into two groups and fed slightly modified American Institute of Nutrition-93 Growing (AIN-93G) diet without (n=10) or with (n=40) dietary Cd (200 ppm) for 8 weeks. To confirm alteration by dietary Cd intake, twenty rats fed AIN-93G diet without (n=10) and with (n=10) dietary Cd were sacrificed and compared. Other thirty rats were randomly blocked into three groups and fed slightly modified AIN-93G diets replacing 0 (n=10), 5 (n=10) or 10% (n=10) chlorella of total kg diet for 4 weeks. Daily food intake, body weight change, body weight gain/calorie intake, organ weight (liver, spleen, and kidney), perirenal fat pad and epididymal fat pad weights were measured. To examine Cd detoxification, urinary Cd excretion and metallothonein (MT) concentrations in kidney and intestine were measured. Food intake, calorie intake, body weight change, body weight gain/calorie intake, organ weight and fat pad weights were decreased by dietary Cd intake. Urinary Cd excretion and MT concentrations in kidney and small intestine were increased by dietary Cd. After given Cd containing diet, food intake, calorie intake, body weight change, body weight gain/calorie intake, organ weights and fat pad weights were not influenced by dietary chlorella intake. Renal MT synthesis tended to be higher in a dose-dependent manner, but not significantly. And chlorella intake did not significantly facilitate renal and intestinal MT synthesis and urinary Cd excretion. These findings suggest that, after stopping cadmium supply, chlorella supplementation, regardless of its percentage, might not improve cadmium detoxification from the body in growing rats.
PMCID: PMC2788181  PMID: 20016707
Chlorella vulgaris; cadmium excretion; metallothionein; Sprague-Dawley rats
19.  Hypoglycemic effect of Chlorella vulgaris intake in type 2 diabetic Goto-Kakizaki and normal Wistar rats 
The aim of this study was to examine the hypoglycemic effect of chlorella in 6 week-old type 2 diabetic Goto-Kakizaki (GK, n=30) rats and 6 week-old normal Wistar (n=30) rats. Animals were randomly assigned to 3 groups respectively, and were fed three different experimental diets containing 0%, 3% or 5% (w/w) chlorella for 8 weeks. In diabetic GK rats, the insulinogenic-indices were not significantly different among the groups. The concentrations of fasting plasma glucagon and hepatic triglyceride, and the insulin/glucagon ratios of the GK-3% chlorella and GK-5% chlorella groups were significantly lower than those of the GK-control group. The HOMA-index and the concentrations of fasting blood glucose and plasma insulin of the GK-3% chlorella and GK-5% chlorella groups were slightly lower than those of the GK-control group. In normal Wistar rats, the insulinogenic-indices were not significantly different among the normal groups, but that of the Wistar-5% chlorella group was slightly higher than the other groups. The concentrations of fasting blood glucose and plasma insulin, and the HOMA-index of the Wistar-5% chlorella group were a little higher, and the fasting plasma glucagon concentration and the insulin/glucagon ratio of the Wistar-5% chlorella group were significantly higher than those of the Wistar-control and Wistar-3% chlorella groups. In conclusion, this study shows that the glucose-stimulated insulin secretion was not affected by the intake of chlorella, which could be beneficial, however, in improving insulin sensitivity in type 2 diabetic GK and normal Wistar rats.
PMCID: PMC2788164  PMID: 20016698
Chlorella; glucagon; Goto-kakizaki rat; insulin; insulin sensitivity
20.  Effect of Chlorella intake on Cadmium metabolism in rats 
This study was performed to investigate the effect of chlorella on cadmium (Cd) toxicity in Cd- administered rats. Sixty male Sprague-Dawley rats (14 week-old) were blocked into 6 groups. Cadmium chloride was given at levels of 0 or 325 mg (Cd: 0, 160 ppm), and chlorella powder at levels of 0, 3 and 5%. Cadmium was accumulated in blood and tissues (liver, kidney and small intestine) in the Cd-exposed groups, while the accumulation of Cd was decreased in the Cd-exposed chlorella groups. Fecal and urinary Cd excretions were remarkably increased in Cd-exposed chlorella groups. Thus, cadmium retention ratio and absorption rate were decreased in the Cd exposed chlorella groups. Urinary and serum creatinine, and creatinine clearance were not changed in experimental animals. In addition, metallothionein (MT) synthesis in tissues was increased by Cd administration. The Cd-exposed chlorella groups indicated lower MT concentration compared to the Cd-exposed groups. Moreover, glomerular filtration rate (GFR) was not changed by dietary chlorella and Cd administration. According to the results above, this study could suggest that Cd toxicity can be alleviated by increasing Cd excretion through feces. Therefore, when exposed to Cd, chlorella is an appropriate source which counteracts heavy metal poisoning, to decrease the damage of tissues by decreasing cadmium absorption.
PMCID: PMC2788161  PMID: 20016697
Chlorella; cadmium; excretion; heavy metal; metallothionein (MT)
21.  Effect of fructose or sucrose feeding with different levels on oral glucose tolerance test in normal and type 2 diabetic rats 
Nutrition Research and Practice  2008;2(4):252-258.
This study was designed to determine whether acute fructose or sucrose administration at different levels (0.05 g/kg, 0.1 g/kg or 0.4 g/kg body weight) might affect oral glucose tolerance test (OGTT) in normal and type 2 diabetic rats. In OGTT, there were no significant differences in glucose responses between acute fructose- and sucrose-administered groups. However, in normal rats, the AUCs of the blood glucose response for the fructose-administered groups tended to be lower than those of the control and sucrose-administered groups. The AUCs of the lower levels fructoseor sucrose-administered groups tended to be smaller than those of higher levels fructose- or sucrose-administered groups. In type 2 diabetic rats, only the AUC of the lowest level of fructose-administered (0.05 g/kg body weight) group was slightly smaller than that of the control group. The AUCs of fructose-administered groups tended to be smaller than those of the sucrose-administered groups, and the AUCs of lower levels fructose-administered groups tended to be smaller than those fed higher levels of fructose. We concluded from this experiment that fructose has tendency to be more effective in blood glucose regulation than sucrose, and moreover, that smaller amount of fructose is preferred to larger amount. Specifically, our experiments indicated that the fructose level of 0.05 g/kg body weight as dietary supplement was the most effective amount for blood glucose regulation from the pool of 0.05 g/kg, 0.1 g/kg and 0.4 g/kg body weights. Therefore, our results suggest the use of fructose as the substitute sweetener for sucrose, which may be beneficial for blood glucose regulation.
PMCID: PMC2788191  PMID: 20016727
Fructose; sucrose; oral glucose tolerance test
22.  Effect of Chlorella vulgaris on lipid metabolism in Wistar rats fed high fat diet 
Nutrition Research and Practice  2008;2(4):204-210.
This study was performed to investigate effects of Chlorella vulgaris on lipid metabolism in rats fed high fat diet. Sixty 6-week-old male Wistar rats were divided into two groups; normal diet group and high fat diet group, then the rats in each group were further divided into three subgroups and fed 0%, 5% and 10% (w/w) chlorella-containing diets, respectively, and raised for 9 weeks. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity and total protein and albumin concentration were not different among groups. Serum total lipids and liver TG concentration were significantly lower in 5% and 10% chlorella groups than 0% chlorella group in high fat diet groups (p<0.05). Serum TG, serum total cholesterol, liver total lipid and liver total cholesterol concentrations were significantly lower in 10% chlorella groups than 0% chlorella group in high fat diet groups (p<0.05). Fecal total lipid, TG and total cholesterol excretions were significantly higher in 5% and 10% chlorella groups than 0% chlorella groups in normal diet and high fat diet groups, respectively (p<0.05). These results suggest that Chlorella vulgaris is effective for prevention of dyslipidemia which may be due to the modulation of lipid metabolism and increased fecal excretion of lipid.
PMCID: PMC2788184  PMID: 20016720
Chlorella vulgaris; serum lipids; high fat diet; Wistar rats
23.  A Dose-Response Relationship between Types of Physical Activity and Distress 
Journal of Korean Medical Science  2008;23(2):218-225.
This study aimed to examine whether a dose-response relationship exists between psychological distress and types of physical activity (total, occupational, and leisure-time). The study subjects (233 men and 313 women) were recruited for a study on cardiovascular disease in the Yangpyeong community located in South Korea. The type and characteristics of physical activity were measured with a modified version of the Stanford 5 city project's questionnaire by well-trained interviewers using a standard protocol. The Psychological Well-being Index-Short Form was used to assess psychological distress. Both the intensity and duration of time in either total physical activity or occupational physical activity (OPA) were not related to the distress score. However, a long duration of time (1 hr/day) in severely intensive (≥6 metabolic equivalent) OPA was related to a high distress score in men (14.1 for none vs. 19.7, p-for-trend=0.005), even after the adjustment for leisure-time physical activity (LTPA). A long duration in time (1 hr/day) in LTPA was related to a lower distress score in men independent of their OPA (16.7 for none vs. 13.1, p-for-trend=0.02). In conclusion, the dose-response relationship of physical activity on psychological distress appeared to differ among the different types of activities. The type of activity may be an important determinant of whether physical activity produces psychological benefits.
PMCID: PMC2526420  PMID: 18437003
Motor Activity; Distress; Dose-Response Relationship
24.  Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1 
Nature genetics  2014;46(8):886-890.
In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified three novel genetic loci associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene, P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene, P = 1.67 × 10−9), and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene, P = 4.25 × 10−8). These associations were replicated in European-ancestry populations including 16,003 cases and 41,335 controls (P = 0.030, 0.004, and 0.010, respectively). Data from the ENCODE project suggest that variants rs4951011 and rs10474352 may be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.
PMCID: PMC4127632  PMID: 25038754
25.  Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats 
International Journal of Nanomedicine  2014;9(Suppl 2):251-260.
The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats.
Silica nanoparticles of two different sizes (20 nm and 100 nm) were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy.
The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex.
The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict potential toxicological effects of silica nanoparticles on target organs.
PMCID: PMC4279759  PMID: 25565843
biological fate; size effect; target organ

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