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.
Metabolic syndrome; Adiposity; Adipokines; Inflammatory cytokines; Abdominal fat
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.
Breast cancer; DNA damage; 4-hydroxyestradiol; oxidative stress; tocopherol
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.
Cystamine; Melanogenesis; Transglutaminase-2; TRP-1; TRP-2; SK-MEL-2 melanoma cells
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.
Metabolic syndrome; food frequency questionnaire; Korean adults; validity; reproducibility
Lactobacillus spp. are associated with the maintenance of reproductive health, but obesity reduces fertility and is a risk factor for obstetric and neonatal complications. We assessed the association between obesity and the cervical Lactobacillus composition, which has not been examined previously. Pyrosequencing was performed using cervical swabs collected from 76 normal participants with negative results for cervical intraepithelial neoplasia (CIN) and 57 participants with CIN, based on histological examinations. Cluster analysis of nine Lactobacillus spp. was performed, and five cluster types were identified. The association between obesity and the Lactobacillus community was assessed by logistic regression analysis after adjustment for confounding factors. The proportion of Lactobacillus iners increased and that of Lactobacillus crispatus decreased according to body mass index (BMI) categories, i.e., underweight (BMI of <18.5 kg m−2), normal weight (BMI of 18.5 to 22.9 kg m−2), overweight (BMI of 23.0 to 24.9 kg m−2), and obese (BMI of ≥25 kg m−2). The L. iners-dominant type had a significant association with obesity (odds ratio [OR], 7.55 [95% confidence interval [CI], 1.18 to 48.2]), compared to the L. crispatus-dominant type. The group with high values for the ratio obtained by dividing the relative abundance of L. iners by that of L. crispatus had a significant association with obesity (OR, 6.54 [95% CI, 1.22 to 35.1]), compared to the low-ratio group. Associations between obesity and the L. iners/L. crispatus ratio were observed among young women (OR, 6.26 [95% CI, 1.15 to 33.9]) but not older women and in the normal group (OR, 6.97 [95% CI, 1.20 to 70.4]) but not the CIN group. Obesity was associated with cervical microflora dominated by L. iners in reproductive-age women without dysplasia.
Cigarette smoking and oral contraceptive (OC) use have been associated with cervical neoplasia, and the combination of smoking and OC use could influence cervical carcinogenesis. We aimed to assess the joint effect of smoking and OC use on the risk of cervical intraepithelial neoplasia (CIN).
From a cohort of human papillomavirus-positive subjects recruited from 6 hospitals in Korea from March 2006 to November 2012, a total of 678 subjects (411 control, 133 CIN 1, and 134 CIN 2 or 3 cases) were selected for this study (mean age, 43 years). The risk of CIN associated with smoking and OC use on additive and multiplicative scales was estimated via multinomial logistic regression after adjustment for potential confounding factors. The relative excess risk due to interaction (RERI) and the synergy index (S) were used to evaluate the additive interaction.
OC users (odds ratio [OR] 1.98; 95% confidence interval [CI], 1.07–3.69) and long-term OC use (≥20 months; OR 2.71; 95% CI, 1.11–6.59) had a higher risk of CIN 2/3, but had no association with CIN 1, compared to non-OC users. Smokers and heavy smoking (≥8 cigarettes/day) were not associated with any CIN grade. Combined smoking and OC use (OR 4.91; 95% CI, 1.68–14.4; RERI/S, 3.77/27.4; P for multiplicative interaction = 0.003) and combined heavy smoking and long-term OC use (OR 11.5; 95% CI, 1.88–70.4; RERI/S, 9.93/18.8; P for multiplicative interaction = 0.009) had a higher risk of CIN 2/3 but had no association with CIN 1 compared to combined non-smoking and non-OC use.
OC use and smoking acted synergistically to increase the risk of CIN 2 or 3 in Korean women.
cervical intraepithelial neoplasia; smoking; oral contraceptive; additive interaction
Studies conducted in Western populations have suggested that dietary calcium may protect against metabolic abnormalities, but there is little evidence of this effect in Asians, who have relatively low calcium intake. We evaluated the cross-sectional relationship between dietary calcium and metabolic syndrome among Korean men and women aged 40 years and over.
A total of 6,375 subjects aged 40 years and over and were recruited between January 2005 and February 2010 from the baseline study of the Multi-Rural Communities Cohort Study in Rural Communities (MRCohort). A food frequency questionnaire was used to collect dietary information. Metabolic syndrome was defined using the modified criteria published in the Third Report of the National Cholesterol Education Program Adult Treatment Panel.
Calcium intake was related inversely to metabolic syndrome in women (P-value = 0.0091), but not in men (P = 0.1842). Among metabolic components, high waist circumference (WC) (P = 0.0426) and high blood glucose (P = 0.0027) in women and hypertriglyceridemia (P = 0.0017) in men were inversely correlated with calcium intake. Excluding those who used calcium or multinutrient supplements did not attenuate the relationship between dietary calcium and metabolic abnormalities.
Dietary calcium intake from foods may be inversely related to metabolic syndrome, WC, and blood glucose among women in rural areas of Korea.
Calcium Intake; milk; metabolic syndrome; Koreans
In vitro experiments using only β-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially α- and β-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with α- and β-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets.
α TC-6 cells and β TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5×105) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS).
α TC-6 and β TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. β TC-1 cells showed both β-β and β-α cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than β TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for β-cells alone (P=0.04). Compared to islets, the α-/β-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09).
α TC-6 and β TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.
α-Cell; β-Cell; Insulin
•We successfully resected 6.5 cm- sized retroperitoneal cystic mass through laparoscopic approach.•Pathologic examination revealed a primary mucinous cystadenoma.•Literature review showed that male sex (p = 0.019), and solid nodules in cysts (p < 0.001) were both significantly associated with malignancy.•When confronted with a cystic mass in the retroperitoneum, a primary mucinous cystic neoplasm should be considered and complete surgical removal of the tumor without spillage is recommended.
Primary retroperitoneal mucinous cystic neoplasm is very rare and its histogenesis is unclear.
Presentation of case
This paper presents the case of a 31-year-old female in whom an incidentally detected retroperitoneal cystic mass, 6.5 cm in size, was successfully resected through laparoscopic approach. Pathologic examination revealed a mucinous cystadenoma. The postoperative course was uneventful, and the patient remained free of recurrence six months after surgery.
Literature review showed that male sex (p = 0.019), and solid nodules in cysts (p < 0.001) were both significantly associated with malignancy.
When confronted with a cystic mass in the retroperitoneum, a primary mucinous cystic neoplasm should be considered and complete surgical removal of the tumor without spillage is recommended.
Primary; Retroperitoneum; Mucinous; Cystadenoma; Laparoscopy
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.
Sodium; potassium; fruits and vegetables; Kimchies; blood pressure
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.
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.
Coronary artery disease; Hemoglobin A, glycosylated
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.
Trans generational; body mass index; daughter; mother; grandmother
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.
Dietary supplements; Preschool; Energy intake
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%.
A1c variability; Coronary artery disease; Diabetes mellitus, type 2
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.
KDS; KNHANES; dietary guidelines; dietary patterns; Korea
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.
Fruit and vegetables (FV); educational level
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.
School tuck shop; healthy eating; intervention program; fruits and vegetables
In human mesenchymal stem cells (hMSCs), toll-like receptor 3 (TLR3) and TLR4 act as key players in the tissue repair process by recognizing their ligands and stimulating downstream processes including cytokine release. The mechanisms of TLR3- and TLR4-mediated cytokine releases from hMSCs remain uncertain. Here, we show that exposure to the TLR3 agonist polyinosinic-polycytidylic acid (poly(I:C)) or incubation with the TLR4 agonist lipopolysaccharide (LPS) increased the mRNA expression levels of TLR3, TLR4 and cytokines in hMSCs. Poly(I:C) exposure rather than LPS incubation not only elevated inositol 1,4,5-triphosphate receptor (IP3R) expression and IP3R-mediated Ca2+ release, but also promoted Orai and STIM expression as well as store-operated Ca2+ entry into hMSCs. In addition, we also observed that 21 Ca2+ signaling genes were significantly up-regulated in response to TLR3 priming of hMSCs by RNA sequencing analysis. Both poly(I:C) and LPS exposure enhanced cytokine release from hMSCs. The enhanced cytokine release vanished upon siRNA knockdown and chelation of intracellular Ca2+. These data demonstrate that TLR3- and TLR4-priming differentially enhance Ca2+ signaling and cytokine expression, and Ca2+ -dependently potentiates cytokine release in hMSCs.
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.
DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population.
A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves.
Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively).
DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.
Cervical Cancer Screening; Cervical Cytology; Cervical Intraepithelial Neoplasia; DNA Methylation; Uterine Cervical Neoplasms
Previously, genetic polymorphisms of C12orf51 (HECTD4) (rs2074356 and/or rs11066280) have been shown to be related to alcohol consumption and type 2 diabetes (T2D). This study aimed to prospectively examine whether C12orf51 had an interaction with or independent effect on alcohol consumption and the risk of T2D. The present study included 3,244 men and 3,629 women aged 40 to 69 years who participated in the Korean Genome and Epidemiology Study (KoGES)_Ansan and Ansung Study. Cox proportional hazards models were used to estimate HRs and 95% CIs for T2D. rs2074356 and rs11066280 were associated with the risk of T2D after adjusting for alcohol consumption (rs2074356 for AA: HR = 0.39 and 95% CI = 0.17–0.87 in men, and HR = 0.36 and 95% CI = 0.13–0.96 in women; rs11066280 for AA: HR = 0.44 and 95% CI = 0.23–0.86 in men, and HR = 0.39 and 95% CI = 0.16–0.94 in women). We identified that the association of each variant (rs2074356 and rs11065756) in C12orf51 was nearly unchanged after adjusted for alcohol consumption. Therefore, the association of 2 SNPs in C12orf51 with diabetes may not be mediated by alcohol use. There was no interaction effect between alcohol consumption and the SNPs with T2D. However, even in never-drinkers, minor allele homozygote strongly influenced T2D risk reduction (rs2074356 for AA: HR = 0.35, 95% CI = 0.14–0.90, and p-trend = 0.0035 in men and HR = 0.34, 95% CI = 0.13–0.93, and p-trend = 0.2348 in women; rs11066280 for AA: HR = 0.36, 95% CI = 0.16–0.82, and p-trend = 0.0014 in men and HR = 0.39, 95% CI = 0.16–0.95, and p-trend = 0.3790 in women), while alcohol consumption did not influence the risk of T2D within each genotype. rs2074356 and rs11066280 in or near C12orf51, which is related to alcohol drinking behavior, may longitudinally decrease the risk of T2D, but not through regulation of alcohol consumption.
Since the 1970s, the public has been advised to limit egg consumption even though there is little evidence of any harmful effect of eggs on blood cholesterol. The purpose of this cross-sectional and prospective study was to evaluate the potential association between egg consumption and metabolic syndrome (MetS) and MetS components in adults ≥ 40 years in KoGES_Yangpyeong. Yangpyeong is a rural area in South Korea. A total of 2,887 subjects (men 1,115, women 1,772) were recruited from 2005 to 2009, based on a physical examination and questionnaires administered using standardized protocol. After excluding subjects who had MetS at baseline, 1,663 subjects (675 men, 958 women) were followed for 3.20 years (range: 0.34–8.70). During the follow-up period, MetS occurred in 289 subjects. More than 3 eggs per week was significantly associated with decreased risk of MetS in both men (RR = 0.46, 95% CI, 0.26–0.82, P for trend = 0.1093) and women (RR = 0.54, 95% CI, 0.31–0.93, P for trend 0.0325) compared to non-users. There was a cross-sectional inverse relationship between egg consumption and abdominal obesity in men and women. Also, prospectively, higher egg consumption in men was associated with a decreased risk of high fasting blood glucose (RR = 0.39, 95% CI, 0.22–0.67, P for trend = 0.0042) and high triglycerides (RR = 0.42, 95% CI, 0.22–0.80, P for trend = 0.1080). In conclusion, our findings suggest that higher egg consumption may reduce the risk of MetS both in men and women, and the risk of high fasting blood glucose and high triglycerides in men. Current guidelines regarding egg consumption may need to be re-visited for healthy middle-aged and elderly people.