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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.  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
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.
PMCID: PMC2808717  PMID: 20090883
Breast cancer; DNA damage; 4-hydroxyestradiol; oxidative stress; tocopherol
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.  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
6.  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
8.  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
9.  β–Hydroxy β–Methylbutyrate Improves Dexamethasone-Induced Muscle Atrophy by Modulating the Muscle Degradation Pathway in SD Rat 
PLoS ONE  2014;9(7):e102947.
Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β–hydroxy β–methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy.
PMCID: PMC4102592  PMID: 25032690
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.  Self-reported Snoring and Carotid Atherosclerosis in Middle-aged and Older Adults: The Korean Multi-Rural Communities Cohort Study 
Journal of Epidemiology  2014;24(4):281-286.
We investigated the relation of self-reported snoring with carotid intima-media thickness (IMT) and plaque in community-dwelling middle-aged and older adults.
In total, 7330 community-dwelling subjects in the Korean Multi-Rural Communities Cohort Study were included in the analysis. Common carotid artery IMT (CCA-IMT) and plaque were evaluated by high-resolution B-mode ultrasonography. Snoring status was evaluated using a structured interview.
Snorers had a significantly greater average CCA-IMT than non-snorers (0.726 vs 0.713 mm; P < 0.001), after adjusting for age and gender. The odds ratios (OR) for high CCA-IMT (fifth quintile) were significantly higher for snorers than for non-snorers in multivariate-adjusted analysis (OR 1.25, 95% confidence interval [CI] 1.10–1.42). However, there was no significant relationship between snoring and carotid plaques.
Our data suggest that self-reported snoring is significantly associated with increased IMT, but not with the presence of plaques. These findings suggest that early screening and intervention for snoring in the general population are needed to prevent adverse cardiovascular events.
PMCID: PMC4074632  PMID: 24727753
snoring; atherosclerosis; carotid intima-media thickness; carotid artery plaque
13.  New Breast Cancer Risk Variant Discovered at 10q25 in East Asian Women 
Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations.
We evaluated nine of those non-replication loci in East Asians in order to identify new risk variants for breast cancer in these regions. First, we analyzed single nucleotide polymorphisms (SNPs) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (Stage 1). In each region we selected a SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (Stage 2). Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants.
Two SNPs were replicated in Stage 2 at P < 0.05: rs1419026 at 6q14 (per allele OR = 1.07, 95% CI: 1.03-1.12, P = 3.0×10−4) and rs941827 at 10q25 (OR = 0.92, 95% CI: 0.89-0.96, P = 5.3×10−5). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR = 0.88, 95% CI: 0.82-0.97, P = 5.3×10−5).
We identified a new breast cancer risk variant at 10q25 in East Asian women.
Results from this study improve the understanding of the genetic basis for breast cancer.
PMCID: PMC3720126  PMID: 23677579
breast cancer; genetic susceptibility; GWAS replication; single nucleotide polymorphism
14.  Elevated Brachial-Ankle Pulse Wave Velocity Is Independently Associated with Microalbuminuria in a Rural Population 
Journal of Korean Medical Science  2014;29(7):941-949.
Microalbuminuria is a marker of generalized endothelial dysfunction resulting from arterial stiffness or insulin resistance, and brachial-ankle pulse wave velocity (baPWV) is a good measure of arterial stiffness. We aimed to investigate whether elevated baPWV is independently associated with microalbuminuria. This study included 1,648 individuals aged over 40 who participated in the baseline Multi-Rural Cohort Study conducted in Korean rural communities between 2005 and 2006. Participants were classified into less than 30 mg/g as normoalbuminuria or 30-300 mg/g as microalbuminuriausing urinary albumin creatinine ratio (UACR). The median and Q1-Q3 baPWV values were significantly higher in the microalbuminuric group both in men (1,538, 1,370-1,777 cm/s vs. 1,776, 1,552-2,027 cm/s, P < 0.001) and women (1,461, 1,271-1,687 cm/s vs. 1,645, 1,473-1,915 cm/s, P < 0.001). BaPWV was independently associated with microalbuminuria in both genders after adjusting for pulse rate; fasting blood glucose; triglyceride; homeostatic model assessment insulin resistance (HOMAIR) and, history of hypertension and diabetes. Fasting blood sugar and HOMAIR were judged as having nothing to do with multicolinearity (r = 0.532, P < 0.001). Elevated baPWV was independently associated with microalbuminuria regardless of insulin resistance among rural subjects over 40 yr.
Graphical Abstract
PMCID: PMC4101782  PMID: 25045226
Albuminuria; Insulin Resistance; Risk Factors; Vascular Stiffness
15.  Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer 
BioMed Research International  2014;2014:132702.
Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed.
PMCID: PMC4094711  PMID: 25050322
16.  Association of Low Muscle Mass and Combined Low Muscle Mass and Visceral Obesity with Low Cardiorespiratory Fitness 
PLoS ONE  2014;9(6):e100118.
Previous studies have shown that low cardiorespiratory fitness (CRF), visceral obesity and low muscle mass may share pathophysiological mechanisms, such as insulin resistance and chronic inflammation. In this study, we investigated whether low CRF is associated with low muscle mass, visceral obesity, and visceral obesity combined with low muscle mass.
Research Design and Methods
The associations between CRF and low muscle mass and combined low muscle mass and visceral obesity were examined in 298 apparently healthy adults aged 20–70 years. Low muscle mass was defined using a skeletal muscle mass index (SMI) that was calculated using dual energy X-ray absorptiometry. Visceral obesity was defined as a visceral fat area (VFA) exceeding 100 cm2 in women and 130 cm2 in men. We classified the participants into 4 low muscle mass/visceral obesity groups according to SMI and VFA. CRF was measured using a cycle ergometer test.
CRF level correlated positively with SMI and negatively with VFA. Individuals with low muscle mass had lower CRF values than those without low muscle mass. After adjustment for age, sex, lifestyle factors, and markers for insulin resistance and inflammation, participants in the lowest quartile of CRF had an odds ratio (OR) for low muscle mass of 4.98 compared with those in the highest quartile (95% confidence interval (CI) = 1.19–12.99; P for trend = 0.001) and an OR for combined low muscle mass and visceral obesity of 31.46 (95% CI = 4.31–229.68; P for trend = 0.001).
Individuals with lower CRF exhibited increased risk of low muscle mass and combined low muscle mass and visceral obesity. These results suggest that low CRF may be a potential indicator for low muscle mass and combined low muscle mass and visceral obesity in Korean adults.
PMCID: PMC4061126  PMID: 24937121
17.  Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls 
Human Molecular Genetics  2013;22(12):2539-2550.
In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations.
PMCID: PMC3658167  PMID: 23535825
18.  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
19.  Chromatin CKAP2, a New Proliferation Marker, as Independent Prognostic Indicator in Breast Cancer 
PLoS ONE  2014;9(6):e98160.
The level of proliferation activity is a strong prognostic or predictive indicator in breast cancer, but its optimal measurement is still in debate, necessitating new proliferation markers. In the present study, the prognostic significance of the CKAP2-positive cell count (CPCC), a new proliferation marker, was evaluated, and the results were compared with those for the mitotic activity index (MAI).
This study included 375 early-stage breast cancer samples collected from two institutions between 2000 and 2006. Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox proportional hazard regression models were fitted to determine the association between the CPCC and relapse-free survival (RFS) amongst three groups formed on the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest values, respectively, and group 1 the lowest.
After adjustment for age, T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor status, institution, and year of surgical resection, the CPCC was associated with a significantly worse RFS {hazard ratio [HR]  = 4.10 (95% CI: 1.64–10.29) for group 2; HR  = 4.35 (95% CI: 2.04–10.35) for group 3}. Moreover, its prognostic significance was similar to or higher than that based on the MAI {HR  = 2.05 (95% CI: 0.94–4.65) for group 2; HR  = 2.35 (95% CI: 1.09–5.10) for group 3}. In subgroup analyses, the CPCC showed a prognostic significance in the luminal A and triple-negative subgroups, but not in the HER2-positive subgroup.
Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast cancer, and could potentially replace the MAI in clinical evaluation of proliferation activity. Additionally, our study results suggest that the prognostic significance of proliferation activity differs among the various subgroups of breast cancer.
PMCID: PMC4041571  PMID: 24887265
20.  Evaluation of Stem Cell Components in Retrocorneal Membranes 
Journal of Korean Medical Science  2014;29(6):846-851.
The purpose of this study was to elucidate the origin and cellular composition of retrocorneal membranes (RCMs) associated with chemical burns using immunohistochemical staining for primitive cell markers. Six cases of RCMs were collected during penetrating keratoplasty. We examined RCMs with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS) staining and immunohistochemical analysis using monoclonal antibodies against hematopoietic stem cells (CD34, CD133, c-kit), mesenchymal stem cells (beta-1-integrin, TGF-β, vimentin, hSTRO-1), fibroblasts (FGF-β, α-smooth muscle actin), and corneal endothelial cells (type IV collagen, CD133, VEGF, VEGFR1). Histologic analysis of RCMs revealed an organized assembly of spindle-shaped cells, pigment-laden cells, and thin collagenous matrix structures. RCMs were positive for markers of mesenchymal stem cells including beta-1-integrin, TGF-β, vimentin, and hSTRO-1. Fibroblast markers were also positive, including FGF-β and α-smooth muscle actin (SMA). In contrast, immunohistochemical staining was negative for hematopoietic stem cell markers including CD34, CD133 and c-kit as well as corneal endothelial cell markers such as type IV collagen, CD133 except VEGF and VEGFR1. Pigment-laden cells did not stain with any antibodies. The results of this study suggest that RCMs consist of a thin collagen matrix and fibroblast-like cells and may be a possible neogenetic structure produced from a lineage of bone marrow-derived mesenchymal stem cells.
Graphical Abstract
PMCID: PMC4055820  PMID: 24932088
Burns, Chemical; Cornea; Mesenchymal Stem Cell; Retrocorneal Membrane
21.  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
22.  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
23.  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
24.  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.
PMCID: PMC3873891  PMID: 24173716
25.  Vitamin D Levels in Children and Adolescents with Antiepileptic Drug Treatment 
Yonsei Medical Journal  2014;55(2):417-421.
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.
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.
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.
PMCID: PMC3936617  PMID: 24532512
Vitamin D; epilepsy; anticonvulsants; developmental disabilities; intellectual disability

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