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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.
doi:10.7762/cnr.2013.2.2.91
PMCID: PMC3728468  PMID: 23908975
Metabolic syndrome; Adiposity; Adipokines; Inflammatory cytokines; Abdominal fat
2.  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.
doi:10.4162/nrp.2010.4.2.121
PMCID: PMC2867222  PMID: 20461200
Metabolic syndrome; food frequency questionnaire; Korean adults; validity; reproducibility
3.  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.
doi:10.4162/nrp.2009.3.3.185
PMCID: PMC2808717  PMID: 20090883
Breast cancer; DNA damage; 4-hydroxyestradiol; oxidative stress; tocopherol
4.  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.
Background
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.
Methods
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).
Results
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).
Conclusion
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.
doi:10.4093/dmj.2014.38.1.58
PMCID: PMC3950196  PMID: 24627829
Coronary artery disease; Hemoglobin A, glycosylated
6.  Dietary Supplements Use and Related Factors of Preschoolers in 3 Korean Cities 
Purpose
To estimate the prevalence of dietary supplement (DS) use, investigate the related factors associated with DS use among preschoolers and support the adequate nutrition.
Methods
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.
Results
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%.
Conclusion
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.
doi:10.5223/pghn.2013.16.2.104
PMCID: PMC3760705  PMID: 24010114
Dietary supplements; Preschool; Energy intake
7.  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.
doi:10.4162/nrp.2012.6.3.263
PMCID: PMC3395793  PMID: 22808352
Fruit and vegetables (FV); educational level
8.  Persistent telomere cohesion triggers a prolonged anaphase 
Molecular Biology of the Cell  2014;25(1):30-40.
Telomeres use distinct mechanisms to mediate cohesion between sister chromatids. However, the motivation for a specialized mechanism is not well understood. Fluorescence in situ hybridization and live-cell imaging show that persistent sister chromatid cohesion at telomeres triggers a prolonged anaphase in normal human cells and cancer cells.
Telomeres use distinct mechanisms (not used by arms or centromeres) to mediate cohesion between sister chromatids. However, the motivation for a specialized mechanism at telomeres is not well understood. Here we show, using fluorescence in situ hybridization and live-cell imaging, that persistent sister chromatid cohesion at telomeres triggers a prolonged anaphase in normal human cells and cancer cells. Excess cohesion at telomeres can be induced by inhibition of tankyrase 1, a poly(ADP-ribose) polymerase that is required for resolution of telomere cohesion, or by overexpression of proteins required to establish telomere cohesion, the shelterin subunit TIN2 and the cohesin subunit SA1. Regardless of the method of induction, excess cohesion at telomeres in mitosis prevents a robust and efficient anaphase. SA1- or TIN2-induced excess cohesion and anaphase delay can be rescued by overexpression of tankyrase 1. Moreover, we show that primary fibroblasts, which accumulate excess telomere cohesion at mitosis naturally during replicative aging, undergo a similar delay in anaphase progression that can also be rescued by overexpression of tankyrase 1. Our study demonstrates that there are opposing forces that regulate telomere cohesion. The observation that cells respond to unresolved telomere cohesion by delaying (but not completely disrupting) anaphase progression suggests a mechanism for tolerating excess cohesion and maintaining telomere integrity. This attempt to deal with telomere damage may be ultimately futile for aging fibroblasts but useful for cancer cells.
doi:10.1091/mbc.E13-08-0479
PMCID: PMC3873891  PMID: 24173716
9.  Vitamin D Levels in Children and Adolescents with Antiepileptic Drug Treatment 
Yonsei Medical Journal  2014;55(2):417-421.
Purpose
This study was to evaluate the relationship of 25(OH)D3 levels with anticonvulsant use and other possible factors in epileptic children and adolescents.
Materials and Methods
We studied 143 patients with epilepsy (90 boys, 53 girls; 11.21±4.49 years), who had been treated with anticonvulsants for more than 1 year. Patients who had taken multiple vitamins before the blood test and those who have the limitation of physical activity (wheelchair-bound) were excluded from the study. We evaluated the difference in vitamin D status according to the type and number of anticonvulsants taken and other factors such as gender, age, intelligence and seizure variables.
Results
For patients with mental retardation or developmental delay, 25(OH)D3 levels were lower than the levels in patients with normal intelligence quotient levels (p=0.03). 25(OH)D3 levels were lower in patients who had taken anticonvulsants for more than 2 years as compared to those who had taken them for less than 2 years (p=0.03). Those taking oxcarbazepine had significantly lower vitamin D levels than patients taking valproic acid (p=0.01). However, no effects of number of anticonvulsants taken were detectable. More than two-thirds of the patients were diagnosed with osteopenia or osteoporosis in patients showing either vitamin D insufficiency or deficiency.
Conclusion
The possibility of vitamin D deficiency can be considered in pediatric patients taking anticonvulsants if they have mental retardation or developmental delay or if they have been taking anticonvulsants for more than 2 years or taking hepatic enzyme inducing drugs.
doi:10.3349/ymj.2014.55.2.417
PMCID: PMC3936617  PMID: 24532512
Vitamin D; epilepsy; anticonvulsants; developmental disabilities; intellectual disability
10.  Effect of renin-angiotensin-system blockers on contrast-medium-induced acute kidney injury after coronary angiography 
Background/Aims
With the increasing incidence of cardiovascular disease, angiocardiography using contrast-enhancing media has become an essential diagnostic and therapeutic tool, despite the risk of contrast-medium-induced acute kidney injury (CIAKI). CIAKI may be exacerbated by renin-angiotensin-system (RAS) blockers, which are also used in a variety of cardiovascular disorders. This study evaluated the effects of RAS blockade on CIAKI after coronary angiography.
Methods
Patients who underwent coronary angiography in our hospital between May 2009 and July 2011 were reviewed. Serum creatinine levels before and after coronary angiography were recorded. CIAKI was diagnosed according to an increase in serum creatinine > 0.5 mg/dL or 25% above baseline.
Results
A total of 1,472 subjects were included in this study. Patients taking RAS blockers were older, had a higher baseline creatinine level, lower estimated glomerular filtration rate (eGFR), and had received a greater volume of contrast medium. After propensity score matching, no difference was observed between the RAS (+) and RAS (.) groups. Multiple logistic regression identified RAS blockade, age, severe heart failure, contrast volume used, hemoglobin level, and eGFR as predictors of CIAKI. Multiple logistic regression after propensity matching showed that RAS blockade was associated with CIAKI (odds ratio, 1.552; p = 0.026).
Conclusions
This study showed that the incidence of CIAKI was increased in patients treated with RAS blockers.
doi:10.3904/kjim.2014.29.2.203
PMCID: PMC3956990  PMID: 24648803
Renin angiotensin system; Coronary angiography; Acute kidney injury
11.  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.
doi:10.4162/nrp.2009.3.3.200
PMCID: PMC2808719  PMID: 20090885
Corn gluten hydrolysate; weight reduction; dietary free amino acids; BCAAs; leucine
12.  Cilostazol inhibits insulin-stimulated expression of sterol regulatory binding protein-1c via inhibition of LXR and Sp1 
Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an important hepatic manifestation of metabolic syndrome. Sterol regulatory binding protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the liver. Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1). Cilostazol is an antiplatelet agent that prevents atherosclerosis and decreases serum triglyceride levels. However, little is known about the effects of cilostazol on hepatic lipogenesis. Here, we examined the role of cilostazol in the regulation of SREBP-1c transcription in the liver. The effects of cilostazol on the expression of SREBP-1c and its target genes in response to insulin or an LXR agonist (T0901317) were examined using real-time RT-PCR and western blot analysis on cultured hepatocytes. To investigate the effect of cilostazol on SREBP-1c at the transcriptional level, transient transfection reporter assays and electrophoretic mobility shift assays (EMSAs) were performed. Cilostazol inhibited insulin-induced and LXR-agonist-induced expression of SREBP-1c and its downstream targets, acetyl-CoA carboxylase and fatty acid synthase, in cultured hepatocytes. Cilostazol also inhibited activation of the SREBP-1c promoter by insulin, T0901317 and Sp1 in a luciferase reporter assay. EMSA analysis showed that cilostazol inhibits SREBP-1c expression by repressing the binding of LXR and Sp1 to the promoter region. These results indicate that cilostazol inhibits insulin-induced hepatic SREBP-1c expression via the inhibition of LXR and Sp1 activity and that cilostazol is a negative regulator of hepatic lipogenesis.
doi:10.1038/emm.2013.143
PMCID: PMC3909891  PMID: 24458133
cilostazol; lipogenesis; LXR; Sp1; SREBP-1c
13.  Olfactomedin 4 Suppresses Tumor Growth and Metastasis of Mouse Melanoma Cells through Downregulation of Integrin and MMP Genes 
Molecules and Cells  2012;34(6):555-561.
Olfactomedin 4 (OLFM4) is highly expressed in gastrointestinal cancers and has an anti-apoptotic function. The roles of OLFM4 in tumor growth and metastasis and how it functions in these processes remain elusive. We investigated the function of OLFM4 in tumor growth and metastasis using B16F10 mouse melanoma cells as an experimental system. Our results showed that OLFM4 had no positive effect on cell viability or cell cycle progression in B16F10 cells. However, it significantly suppressed the tumorigenicity of B16F10 cells, i.e., intradermal primary tumor growth and lung metastasis. OLFM4 also suppressed the migration and invasion of B16F10 cells in vitro. For further insight into the mechanisms underlying OLFM4-mediated suppression of tumor progression, we examined the effect of OLFM4 on the expression of integrin and matrix metalloproteinase (MMP), both of which are involved in tumor progression. Overexpression of OLFM4 clearly reduced the expression levels of integrin α1, integrin α4, integrin α5, integrin α6, and MMP9. Moreover, forced expression of MMP9 attenuated the inhibitory activity of OLFM4 on migration and invasiveness. Our findings provide the experimental evidence that OLFM4 may function as a tumor suppressor and an anti-metastatic gene during tumor progression.
doi:10.1007/s10059-012-0251-7
PMCID: PMC3887829  PMID: 23161172
B16F10 cells; cancer; metastasis; OLFM4; tumor growth
14.  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.
doi:10.4162/nrp.2009.3.2.89
PMCID: PMC2788181  PMID: 20016707
Chlorella vulgaris; cadmium excretion; metallothionein; Sprague-Dawley rats
15.  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.
doi:10.4162/nrp.2009.3.1.23
PMCID: PMC2788164  PMID: 20016698
Chlorella; glucagon; Goto-kakizaki rat; insulin; insulin sensitivity
16.  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.
doi:10.4162/nrp.2009.3.1.15
PMCID: PMC2788161  PMID: 20016697
Chlorella; cadmium; excretion; heavy metal; metallothionein (MT)
17.  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.
doi:10.4162/nrp.2008.2.4.252
PMCID: PMC2788191  PMID: 20016727
Fructose; sucrose; oral glucose tolerance test
18.  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.
doi:10.4162/nrp.2008.2.4.204
PMCID: PMC2788184  PMID: 20016720
Chlorella vulgaris; serum lipids; high fat diet; Wistar rats
19.  Correction: The Autophagy-Related Marker LC3 Can Predict Prognosis in Human Hepatocellular Carcinoma 
PLoS ONE  2013;8(12):10.1371/annotation/154eb7f6-687c-4416-afc6-006658035c57.
doi:10.1371/annotation/154eb7f6-687c-4416-afc6-006658035c57
PMCID: PMC3870008
20.  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.
doi:10.3346/jkms.2008.23.2.218
PMCID: PMC2526420  PMID: 18437003
Motor Activity; Distress; Dose-Response Relationship
21.  The Autophagy-Related Marker LC3 Can Predict Prognosis in Human Hepatocellular Carcinoma 
PLoS ONE  2013;8(11):e81540.
Background
Defects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein.
Methodology
The expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis.
Principal Findings
LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (p = 0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33–0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045) and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers.
Conclusion
Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.
doi:10.1371/journal.pone.0081540
PMCID: PMC3839913  PMID: 24282606
22.  Lower Zinc Bioavailability May Be Related to Higher Risk of Subclinical Atherosclerosis in Korean Adults 
PLoS ONE  2013;8(11):e80115.
Background
There is a proposed link between dietary zinc intake and atherosclerosis, but this relationship remains unclear. Phytate may contribute to this relationship by influencing zinc bioavailability.
Objective
The aim of this study is to examine the relationship between zinc bioavailability and subclinical atherosclerosis in healthy Korean adults.
Materials and Methods
The present cross-sectional analysis used baseline data from the Korean multi-Rural Communities Cohort Study (MRCohort), which is a part of The Korean Genome Epidemiology Study (KoGES). A total of 5,532 subjects (2,116 men and 3,416 women) aged 40 years and older were recruited from rural communities in South Korea between 2005 and 2010. Phytate:zinc molar ratio, estimated from a food-based food frequency questionnaire (FFQ) of 106 food items, was used to determine zinc bioavailability, and carotid intima media thickness (cIMT) and pulse wave velocity (PWV) were measured to calculate the subclinical atherosclerotic index.
Results
We found that phytate:zinc molar ratio is positively related to cIMT in men. A higher phytate:zinc molar ratio was significantly related to an increased risk of atherosclerosis in men, defined as the 80th percentile value of cIMT (5th vs. 1st quintile, OR = 2.11, 95% CI 1.42-3.15, P for trend = 0.0009), and especially in elderly men (5th vs. 1st quintile, OR = 2.58, 95% CI 1.52-4.37, P for trend = 0.0021). We found a positive relationship between phytate:zinc molar ratio and atherosclerosis risk among women aged 65 years or younger. Phytate:zinc molar ratio was not found to be related to PWV.
Conclusions
Lower zinc bioavailability may be related to higher atherosclerosis risk.
doi:10.1371/journal.pone.0080115
PMCID: PMC3819296  PMID: 24223217
23.  Macronutrient Composition and Sodium Intake of Diet Are Associated with Risk of Metabolic Syndrome and Hypertension in Korean Women 
PLoS ONE  2013;8(10):e78088.
Hypertension and hypertriglycemia are the most important contributors to metabolic syndrome (MetS) and cardiovascular disease risk in South Koreans with a relatively lean body mass. These major contributors differ from those identified in Western populations. This study aimed to identify the characteristics of the Korean diet associated with increased risk of MetS, whose prevalence has been steadily increasing in South Korea. On the basis of data collected from 5,320 subjects by the 2007–2008 Korean National Health and Nutrition Examination Survey, 3 dietary patterns were identified using factor analysis and their association with the risk of MetS and its components was examined. The balanced Korean diet, a typical Korean diet of rice and kimchi intake supplemented by a variety of foods had a desirable macronutrient composition and was associated with a lower risk of elevated blood pressure (OR=0.61, 95% CI=0.45–0.84) and hypertriglyceridemia (0.69, 0.49–0.88) in men and a lower risk of elevated blood pressure (0.59, 0.41–0.85) and MetS (0.67, 0.47–0.96) in women. The unbalanced Korean diet, characterized by a high intake of carbohydrates and sodium and little variety, was associated with a higher risk of MetS (1.44, 1.03–2.01) and elevated blood pressure (1.41, 1.00–1.98) in women. The semi-western diet, characterized by a relatively high intake of meat, poultry, and alcohol, was associated with a lower risk of low high-density lipoprotein cholesterol (0.70, 0.54–0.89) in women. Thus, macronutrient composition and sodium intake are associated with the risk of MetS and prehypertension in women. Maintaining a desirable macronutrient composition and avoiding excessive consumption of carbohydrates and sodium should be emphasized for prevention of MetS and hypertension in South Korean women.
doi:10.1371/journal.pone.0078088
PMCID: PMC3808273  PMID: 24205105
24.  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.
doi:10.4162/nrp.2013.7.5.400
PMCID: PMC3796666  PMID: 24133620
Trans generational; body mass index; daughter; mother; grandmother
25.  Differential Protective Effects of Exenatide, an Agonist of GLP-1 Receptor and Piragliatin, a Glucokinase Activator in Beta Cell Response to Streptozotocin-Induced and Endoplasmic Reticulum Stresses 
PLoS ONE  2013;8(9):e73340.
Background
Agonists of glucagon-like peptide-1 receptor (GLP-1R) and glucokinase activators (GKA) act as antidiabetic agents by their ability protect beta cells, and stimulate insulin secretion. Oxidative and endoplasmic reticulum (ER) stresses aggravate type 2 diabetes by causing beta cell loss. It was shown that GLP-1R agonists protect beta cells from oxidative and ER stresses. On the other hand, little is known regarding how GKAs protect beta cells. We hypothesized that GKAs protect beta cells by mechanisms distinct from those underlying GLP-1R agonist and tested our hypothesis by comparing the molecular effects of exenatide, a GLP-1R agonist, and piragliatin, a GKA, on INS-1 cells under oxidative and ER-induced stresses.
Methods
Beta cells were treated with streptozotocin (STZ) to induce oxidative stress and with palmitate or thapsigargin (Tg) to induce ER stress respectively, and the effects of exenatide and piragliatin on these cells were investigated by: a) characterizing the kinases involved employing specific kinase inhibitors, and b) by identifying the differentially regulated proteins in response to stresses with proteomic analysis.
Results
Exenatide protected INS-1 cells from both ER and STZ-induced death. In contrast, piragliatin rescued the cells only from STZ-induced stress. Akt activation by exenatide appeared to contribute to its protective effects of beta cells while enhanced glucose utilization was the contributing factor in the case of piragliatin. Also, exenatide, not piragliatin, blocked changes in proteins 14-3-3β, ε and θ, and preserved the 14-3-3θ levels under the ER stress. Isoform-specific modifications of 14-3-3, and the reduction of 14-3-3θ, commonly associated with beta cell death were assessed.
Conclusions
Exenatide and piragliatin exert distinct effects on beta cell survival and thus on type 2 diabetes. This study which confirmed our hypothesis is also the first to observe specific modulation of 14-3-3 isoform in stress-induced beta cell death associated with progressive deterioration of type 2 diabetes.
doi:10.1371/journal.pone.0073340
PMCID: PMC3777936  PMID: 24069189

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