Background and Objectives: To evaluate the impact of smoking in young adults on the risk of cardiovascular disease (CVD) and the clustering effect of behavioral risk factors such as smoking, obesity, and depression. Methods: A Korean nationwide population-based cohort of a total of 3,280,826 participants aged 20–39 years old who underwent 2 consecutive health examinations were included. They were followed up until the date of CVD (myocardial infarction [MI] or stroke), or December 2018 (median, 6 years). Results: Current smoking, early age of smoking initiation, and smoking intensity were associated with an increased risk of CVD incidence. Even after quitting smoking, the risk of MI was still high in quitters compared with non-smokers. Cigarette smoking, obesity, and depression were independently associated with a 1.3–1.7 times increased risk of CVD, and clustering of 2 or more of these behavioral risk factors was associated with a 2–3 times increased risk of CVD in young adults. Conclusions In young adults, cigarette smoking was associated with the risk of CVD, and the clustering of 2 or more behavioral risk factors showed an additive risk of CVD.

Background: Although obesity differs according to ethnicity, it is globally established as a solid risk factor for cardiovascular disease. However, it is not fully understood how obesity parameters affect the progression of coronary artery calcification (CAC) in Korean population. We sought to evaluate the association of obesity-related parameters including visceral adipose tissue (VAT) measurement and CAC progression. Methods: This retrospective observational cohort study investigated 1,015 asymptomatic Korean subjects who underwent serial CAC scoring by computed tomography (CT) with at least 1-year interval and adipose tissue measurement using non-contrast CT at baseline for a routine checkup between 2003 and 2015. CAC progression, the main outcome, was defined as a difference of ≥2.5 between the square roots of the baseline and follow-up CAC scores using Agatston units. Results: During follow-up (median 39 months), 37.5% of subjects showed CAC progression of a total population (56.4 years, 80.6% male). Body mass index (BMI) ≥25 kg/m2, increasing waist circumferences (WC), and higher VAT/subcutaneous adipose tissue (SAT) area ratio were independently associated with CAC progression. Particularly, predominance of VAT over SAT at ≥30% showed the strongest prediction for CAC progression (adjusted hazard ratio, 2.20; P<0.001) and remained of prognostic value regardless of BMI or WC status. Further, it provided improved risk stratification of CAC progression beyond known prognosticators. Conclusion Predominant VAT area on CT is the strongest predictor of CAC progression regardless of BMI or WC in apparently healthy Korean population. Assessment of body fat distribution may be helpful to identify subjects at higher risk.

Background: Although obesity differs according to ethnicity, it is globally established as a solid risk factor for cardiovascular disease. However, it is not fully understood how obesity parameters affect the progression of coronary artery calcification (CAC) in Korean population. We sought to evaluate the association of obesity-related parameters including visceral adipose tissue (VAT) measurement and CAC progression. Methods: This retrospective observational cohort study investigated 1,015 asymptomatic Korean subjects who underwent serial CAC scoring by computed tomography (CT) with at least 1-year interval and adipose tissue measurement using non-contrast CT at baseline for a routine checkup between 2003 and 2015. CAC progression, the main outcome, was defined as a difference of ≥2.5 between the square roots of the baseline and follow-up CAC scores using Agatston units. Results: During follow-up (median 39 months), 37.5% of subjects showed CAC progression of a total population (56.4 years, 80.6% male). Body mass index (BMI) ≥25 kg/m2, increasing waist circumferences (WC), and higher VAT/subcutaneous adipose tissue (SAT) area ratio were independently associated with CAC progression. Particularly, predominance of VAT over SAT at ≥30% showed the strongest prediction for CAC progression (adjusted hazard ratio, 2.20; P<0.001) and remained of prognostic value regardless of BMI or WC status. Further, it provided improved risk stratification of CAC progression beyond known prognosticators. Conclusion Predominant VAT area on CT is the strongest predictor of CAC progression regardless of BMI or WC in apparently healthy Korean population. Assessment of body fat distribution may be helpful to identify subjects at higher risk.

A pregnane steroid, 3α-hydroxy-pregn-7-ene-6,20-dione (1), was isolated from a Hydractinia-associated Cladosporium sphaerospermum SW67 by repetitive column chromatographic separation and highperformance liquid chromatography (HPLC) purification. The planar structure of 1 was elucidated from the analysis of the spectroscopic data (1D and 2D NMR spectra) and LC-MS data. The absolute configuration of 1 was determined by interpretation of ROESY spectrum of 1, together with the comparison of reported spectroscopic values in previous studies. To the best of our knowledge, this is the first report of the identification of the pregnane scaffold from C. sphaerospermum, a natural source. Compound 1 was evaluated for its effects on lipid metabolism and adipogenesis during adipocyte maturation and showed that compound 1 substantially inhibited lipid accumulation compared to the control. Consistently, the expression of the adipocyte marker gene (Adipsin) was reduced upon incubation with 1. Further, we evaluated the effects of 1 on lipid metabolism by measuring the transcription of lipolytic and lipogenic genes. The expression of the lipolytic gene ATGL was significantly elevated upon exposure to 1 during adipogenesis, whereas the expression of lipogenic genes FASN and SREBP1 was significantly reduced upon treatment with 1. Thus, our findings provide experimental evidence that the steroid derived from Hydractinia-associated C. sphaerospermum SW67 is a potential therapeutic agent for obesity.

Objective: : Radiation is known to induce autophagy in malignant glioma cells whether it is cytocidal or cytoprotective.Dexamethasone is frequently used to reduce tumor-associated brain edema, especially during radiation therapy. The purpose of the study was to determine whether and how dexamethasone affects autophagy in irradiated malignant glioma cells and to identify possible intervening molecular pathways. Methods: : We prepared p53 mutant U373 and LN229 glioma cell lines, which varied by phosphatase and tensin homolog (PTEN) mutational status and were used to make U373 stable transfected cells expressing GFP-LC3 protein. After performing cell survival assay after irradiation, the IC50 radiation dose was determined. Dexamethasone dose (10 µM) was determined from the literature and added to the glioma cells 24 hours before the irradiation. The effect of adding dexamethasone was evaluated by cell survival assay or clonogenic assay and cell cycle analysis. Measurement of autophagy was visualized by western blot of LC3-I/LC3-II and quantified by the GFP-LC3 punctuated pattern under fluorescence microscopy and acridine orange staining for acidic vesicle organelles by flow cytometry. Results: : Dexamethasone increased cell survival in both U373 and LN229 cells after irradiation. It interfered with autophagy after irradiation differently depending on the PTEN mutational status : the autophagy decreased in U373 (PTEN-mutated) cells but increased in LN229 (PTEN wild-type) cells. Inhibition of protein kinase B (AKT) phosphorylation after irradiation by LY294002 reversed the dexamethasone-induced decrease of autophagy and cell death in U373 cells but provoked no effect on both autophagy and cell survival in LN229 cells. After ATG5 knockdown, radiation-induced autophagy decreased and the effect of dexamethasone also diminished in both cell lines. The diminished autophagy resulted in a partial reversal of dexamethasone protection from cell death after irradiation in U373 cells; however, no significant change was observed in surviving fraction LN229 cells. Conclusion : Dexamethasone increased cell survival in p53 mutated malignant glioma cells and increased autophagy in PTENmutant malignant glioma cell but not in PTEN-wildtype cell. The difference of autophagy response could be mediated though the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway.

BACKGROUND AND OBJECTIVES: Coronary artery calcium (CAC) scoring in the asymptomatic population can improve cardiovascular risk prediction. We aimed to assess CAC progression and the impact of coronary risk factors on the CAC progression rate in asymptomatic Korean individuals with a baseline CAC score of zero. METHODS: The study population was derived from the Korea Initiatives on Coronary Artery Calcification (KOICA) registry: a retrospective, single ethnicity, multicenter registry of asymptomatic individuals who underwent CAC scoring as a part of a health checkup. Individuals with at least two CAC scores and an initial score of zero were included. CAC progression was defined as [√CAC score (follow-up) − √CAC score (baseline)] ≥2.5. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk was calculated. RESULTS: Among 6,268 participants (mean age, 48.0±7.1 years; male, 80.5%), 719 (11.5%) experienced CAC progression during follow-up (median, 109 months; interquartile range, 78–208 months). The CAC progression rate was 0.3%, 1.9%, 4.3%, 8.6%, and 16.7% in years 1–5, respectively. The chance of CAC progression at 5 years was 13.1%, 22.0%, and 27.9% for individuals with a 10-year ASCVD risk of <5%, ≥5% but <7.5%, and ≥7.5%, respectively. A multivariable analysis revealed age, male sex, waist circumference, diabetes, and low-density lipoprotein cholesterol level as independently associated with annualized CAC progression (p<0.001, p=0.017, p=0.025, p=0.032, and p=0.003, respectively). CONCLUSIONS: The probability of CAC progression is very low in Korean individuals with a CAC score of zero. However, the risk of CAC progression increases nonlinearly over time, and increases as the 10-year ASCVD risk increases.
Calcium ; Cardiovascular Diseases ; Cholesterol ; Coronary Vessels ; Follow-Up Studies ; Humans ; Korea ; Lipoproteins ; Male ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Waist Circumference

Transglutaminase 2 (TGase 2) plays a key role in p53 regulation, depleting p53 tumor suppressor through autophagy in renal cell carcinoma. We found that microtubule-associated protein 1A/1B-light chain 3 (LC3), a hallmark of autophagy, were tightly associated with the level of TGase 2 in cancer cells. TGase 2 overexpression increased LC3 levels, and TGase 2 knockdown decreased LC3 levels in cancer cells. Transcript abundance of LC3 was inversely correlated with level of wild type p53. TGase 2 knockdown using siRNA, or TGase 2 inhibition using GK921 significantly reduced autophagy through reduction of LC3 transcription, which was followed by restoration of p53 levels in cancer cells. TGase 2 overexpression promoted the autophagy process by LC3 induction, which was correlated with p53 depletion in cancer cells. Rapamycin-resistant cancer cells also showed higher expression of LC3 compared to the rapamycin-sensitive cancer cells, which was tightly correlated with TGase 2 levels. TGase 2 knockdown or TGase 2 inhibition sensitized rapamycin-resistant cancer cells to drug treatment. In summary, TGase 2 induces drug resistance by potentiating autophagy through LC3 induction via p53 regulation in cancer.
Autophagy* ; Carcinoma, Renal Cell ; Drug Resistance ; RNA, Small Interfering

BACKGROUND AND OBJECTIVES: Coronary artery calcium (CAC) scoring in the asymptomatic population can improve cardiovascular risk prediction. We aimed to assess CAC progression and the impact of coronary risk factors on the CAC progression rate in asymptomatic Korean individuals with a baseline CAC score of zero. METHODS: The study population was derived from the Korea Initiatives on Coronary Artery Calcification (KOICA) registry: a retrospective, single ethnicity, multicenter registry of asymptomatic individuals who underwent CAC scoring as a part of a health checkup. Individuals with at least two CAC scores and an initial score of zero were included. CAC progression was defined as [√CAC score (follow-up) −√CAC score (baseline)] ≥2.5. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk was calculated. RESULTS: Among 6,268 participants (mean age, 48.0±7.1 years; male, 80.5%), 719 (11.5%) experienced CAC progression during follow-up (median, 109 months; interquartile range, 78–208 months). The CAC progression rate was 0.3%, 1.9%, 4.3%, 8.6%, and 16.7% in years 1–5, respectively. The chance of CAC progression at 5 years was 13.1%, 22.0%, and 27.9% for individuals with a 10-year ASCVD risk of <5%, ≥5% but <7.5%, and ≥7.5%, respectively. A multivariable analysis revealed age, male sex, waist circumference, diabetes, and low-density lipoprotein cholesterol level as independently associated with annualized CAC progression (p<0.001, p=0.017, p=0.025, p=0.032, and p=0.003, respectively). CONCLUSIONS The probability of CAC progression is very low in Korean individuals with a CAC score of zero. However, the risk of CAC progression increases nonlinearly over time, and increases as the 10-year ASCVD risk increases.

BACKGROUND: The present study aimed at identifying the difference in the risk of microalbuminuria among individuals with various obesity phenotypes in terms of metabolic health and obesity. METHODS: This cross-sectional study included 15,268 individuals and used data from the National Health and Nutrition Survey conducted from 2011 to 2014. Obesity was defined as body mass index ≥25 kg/m2. Metabolically unhealthy was defined as meeting two or more of the following criteria: systolic and diastolic blood pressure ≥130/85 mm Hg or current use of hypertensive drugs; triglyceride level ≥150 mg/dL; high-density lipoprotein level < 40/50 mg/dL (in both men and women); and fasting blood glucose level ≥100 mg/dL or current use of oral antidiabetic medications. The participants were further classified into four subgroups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). RESULTS: A significant difference was observed in the microalbuminuria ratio among the four groups. The MHNO group was considered as the reference group, and the MHO, MUNO, and MUO groups were at an increased risk for microalbuminuria by 1.42 fold (95% confidence interval [95% CI], 1.03–1.96), 2.02 fold (95% CI, 1.61–2.53), and 3.40 fold (95% CI, 2.70–4.26), respectively, after adjusting confounding factors. CONCLUSION: The MUNO group had a higher risk of developing microalbuminuria than the MHNO group. Thus, based on this result, differences were observed in the risk of developing microalbuminuria among individuals with various obesity subtypes.
Albuminuria ; Blood Glucose ; Blood Pressure ; Body Mass Index ; Creatinine ; Cross-Sectional Studies ; Fasting ; Humans ; Lipoproteins ; Male ; Metabolic Diseases ; Nutrition Surveys* ; Obesity* ; Phenotype* ; Triglycerides