Effect of Korean Red Ginseng on Plasma Ceramide Levels in Postmenopausal Women with Hypercholesterolemia: A Pilot Randomized Controlled Trial

Cardiovascular disease (CVD) is a crucial cause of death in postmenopausal women. Plasma ceramide concentrations are correlated with the development of atherosclerosis and are significant predictors of CVD. Here, we conducted a 4-week, double-blinded, placebo-controlled clinical pilot study to investigate the effect of Korean red ginseng (KRG) on serum ceramide concentrations in 68 postmenopausal women with hypercholesterolemia. Patients were randomly assigned to two groups: the experimental group (n = 36) received KRG and the control (n = 32) group received placebo, 2 g each, once daily. Serum ceramides were measured using liquid chromatography-tandem mass spectrometry at baseline and study completion, with changes in serum ceramide levels as the primary end point. We detected significantly greater mean changes in C16 ceramide levels (d18:1/16:0: -6.4 ± 6.3 pmol/mL vs. 14.6 ± 6.8 pmol/mL, respectively, p = 0.040; d18:1/22:0: -20.8 ± 24.4 pmol/mL vs. 71.1 ± 26.2 pmol/mL, respectively, p = 0.020). Additionally, changes in the median C16 (d18:1/16:0) and C22 (d18:1/22:0) ceramide levels were significantly greater in KRG-group subjects with metabolic syndrome than those without. Therefore, we found that KRG decreases the serum levels of several ceramides in postmenopausal women with hypercholesterolemia, suggesting it may be beneficial for preventing CVD in these individuals.ope

Relationship Ketonuria and Dyslipidemia in Korean Adults Aged 20 Years and Older

Background: In various studies, the presence of ketonuria after at least an 8-hr fast is known to be possibly indicative of metabolic superiority. All metabolic parameters (including body weight, waist circumference, fasting glucose level, blood pressure, insulin level, high-density lipoprotein level, and triglyceride level) were more favorable in the ketonuria group than in the non-ketonuria group. In this study, we investigated the association between ketonuria and dyslipidemia. Methods: We analyzed data from the 2013–2015 Korea National Health and Nutrition Examination Survey. Of the 17,780 people who participated in the survey, 9,269 were selected. The relationship of ketonuria with dyslipidemia was assessed using multivariable logistic regression analysis. Results: The prevalence of dyslipidemia in the ketonuria-positive group was statistically significantly lower than that in the non-ketonuria group. Of the study subjects, 11.2% had hypercholesterolemia, 10.1% had hypertriglyceridemia, 22.4% had hypo-high-density lipoprotein cholesterolemia, and 10% had higher-low-density lipoprotein cholesterolemia. Ketonuria was associated with a lower risk of hypertriglyceridemia (odds ratio 0.620, 95% confidence interval 0.430–0.896) and hypo-high-density lipoprotein cholesterolemia (odds ratio 0.714, 95% confidence interval 0.551–0.926), after adjusting for confounding variables. Conclusion: The risk of dyslipidemia was lower in the ketonuria group than in the non-ketonuria group. The presence of ketonuria is associated with the prevalence of dyslipidemia and the development of hypertriglyceridemia and hypo-high-density lipoprotein cholesterolemia.ope

Effect of Korean Red Ginseng on Cholesterol Metabolites in Postmenopausal Women with Hypercholesterolemia: A Pilot Randomized Controlled Trial

Korean red ginseng (KRG) is known to exert beneficial effects on cardiovascular health. Meanwhile, reduced estrogen at menopause has been shown to have various adverse impacts on cardiovascular risk factors, including blood lipids. The aim of this pilot study was to investigate the effect of KRG on cholesterol metabolites, which are surrogate markers of cholesterol absorption and biosynthesis, in postmenopausal women with hypercholesterolemia. The present study is an exploratory study which used data from a 4-week, double-blinded, placebo-controlled clinical pilot study in 68 postmenopausal women with hypercholesterolemia. Patients received KRG (2 g) or placebo (2 g) once daily. The primary endpoints were changes in the levels of nine sterols. Serum sterols were analyzed using liquid chromatography-mass spectrometry (LC-MS)/MS analysis. Among the sterols, reduction in cholesterol level were significantly larger in the KRG group than in the placebo group (the changes: -148.3 ± 261.1 nmol/mL in the ginseng group vs. -23.0 ± 220.5 nmol/mL in the placebo group, p = 0.039). Additionally, changes in 7-hydroxycholesterol (7-OHC) were significantly larger in the KRG group than in the placebo group (the changes: -0.05 ± 0.09 nmol/mL in the ginseng group vs. -0.002 ± 0.1 nmol/mL in the placebo group, p = 0.047). Oxysterols, cholesterol derivates, have been known to play a role in chronic inflammation diseases such as cardiovascular diseases. KRG improves sterol metabolism by decreasing cholesterol and 7-OHC levels in postmenopausal women with hypercholesterolemia.ope

Relationship of Heart Rate Variability with Triglyceride-Glucose Index among Korean Men and Women in a Primary Care Clinic

Background: Reduced heart rate variability (HRV) can be a predictor of all causes of death. Few studies have analyzed the association between HRV and the triglyceride-glucose (TyG) index in a primary care setting rather than in specific high-risk patients. This study aimed to investigate the relationship between HRV and the TyG index among Koreans at a primary care clinic. Methods: This cross-sectional study included 1,991 participants who underwent HRV assessments and blood tests after fasting for more than 8 hours. Common HRV indices such as the standard deviation of normal-to-normal intervals (SDNN), the root mean square of successive difference (RMSSD), total power (TP), low frequency (LF), high frequency (HF), and the LF/HF ratio were measured. Individuals with a TyG index greater than 9.1 (≥75th percentile) were subclassified into a “high TyG index” group. Associations between the TyG index and HRV were investigated using multiple logistic regression analysis. Results: The individuals’ mean age was 46.6 years, and the high TyG index group included 244 of all 1,991 participants. Among the assessed HRV indices, the SDNN, RMSSD, and HF showed associations with the high TyG index group, with odd ratios of 0.98 (0.97–0.99), 0.98 (0.96–0.99), and 0.99 (0.99–1.00), respectively, after adjusting for age, sex, white blood cell count, total cholesterol, high density lipoprotein cholesterol, alanine aminotransferase, γ-glutamyltransferase, uric acid, creatinine, hypertension, and diabetes. Conclusion: Among the common HRV indices, the SDNN, RMSSD, and HF were decreased in a subgroup of individuals with a high TyG index.ope

효율적인 산소 발생 반응을 위한 망간 산화물 나노 입자에 대한 연구: 재료의 결정구조와 나노 사이즈가 촉매 특성에 미치는 영향

학위논문 (석사)-- 서울대학교 대학원 : 재료공학부, 2016. 2. 남기태.Development of outstanding oxygen evolution reaction(OER) catalyst is essential for efficient hydrogen gas production which is attractive sustainable energy in the future. For this reason, various manganese oxides with bulk scale have been developed and investigated. However, OER activity of conventional manganese oxides in neutral condition is still poor. Thus, our group solved the low activity issue of bulk manganese oxides by introducing MnO nanoparticles in previous research. In this research, we tried to investigate the effect of crystal structure on the OER activity of manganese oxide nanoparticles for more activity enhancement. To clearly see the effect of crystal structure, manganese oxide nanoparticles with various crystal structure(Mn3O4, Mn5O8 and Mn2O3) were obtained with little morphology change via the controlled oxidation of MnO nanoparticles. The oxygen evolution reaction (OER) properties of manganese oxide nanoparticles were evaluated using cyclic voltammetry (CV). Mn3O4 and Mn2O3 nanoparticles showed similar activity and Mn5O8 nanoparticles showed less active property than Mn3O4 and Mn2O3. This observation indicates that effect of crystal structure on OER activity of Mn oxides is significantly reduced in nano scale. To understand the origin of different OER activity between Mn5O8 and other nanoparticles, electrokinetics and redox peak analysis were conducted. As a result, Mn5O8 showed different mechanism (1 electron, 2 proton involved in the reaction before rate determining step) from Mn3O4 and Mn2O3 (1 electron, 1 proton involved in the reaction before rate determining step), which may cause less active property of Mn5O8. Next, we found that manganese oxide nanoparticles have much higher OER activity than bulk manganese oxide materials. Thus, Mn5O8 materials, which has never been investigated as OER catalyst, were further studied to understand why nanoparticles are more active catalyst than bulk manganese oxides. BET analysis and mass activity comparison clearly showed that Mn5O8 nanoparticles have much higher catalytic activity than micron sized Mn5O8 although surface area effect is considered. In addition, catalytic stability is also enhanced in nanoparticles. These results imply that intrinsic catalytic property can be improved as particle size becomes nanoscale. To find the clue of this intrinsic difference, we conducted EPR analysis to observe valence behavior of Mn5O8 materials. As a result, we found that Mn5O8 nanoparticles and micron sized particles have different Mn3+ stability during OER catalysis which may cause intrinsic OER property difference between Mn5O8 materials. In this research, we could understand the effect of crystal structure and nano size on OER activity. Understanding those effect is important because they will be a valuable guide to develop outstanding nano sized OER catalyst in neutral condition. Therefore, further research should be conducted to understand completely the effect of crystal structure in nano scale and nano size on the OER activity.Chapter 1 Introduction 1 1.1 Upcoming hydrogen energy era 1 1.2 Water splitting and necessity of OER catalysts 3 1.3 Types of OER catalysts 7 1.3.1 Noble metal based OER catalyst 7 1.3.2 Transition metal based OER catalyst 9 1.4 Manganese based OER catalyst 12 1.4.1 Mn4CaO5 cluster in Photosystem II 12 1.4.2 Artificial Mn based OER catalysts and their limits 13 Chapter 2 Experimental Procedures 19 2.1 Synthesis of various Mn oxide materials 19 2.1.1 Materials 19 2.1.2 Synthesis of MnO nanoparticles 19 2.1.3 Synthesis of Mn3O4, Mn2O3 and Mn5O8 nanoparticles 23 2.1.4 Synthesis of micron sized Mn5O8 particles 23 2.2 Characterization 25 2.2.1 Powder X-ray diffraction (PXRD) 25 2.2.2 Scanning electron microscopy (SEM) 25 2.2.3 Transmission electron microscopy (TEM) 26 2.2.4 Brunauer-Emmett-Teller (BET) method 26 2.3 Electrochemical analysis 27 2.3.1 Cyclic voltammetry (CV) 27 2.3.2 Bulk electrolysis (BE) 28 2.3.3 Faradaic efficiency measurement 28 2.3.4 Preparation of working electrode 28 2.4 Electron Paramagnetic Resonance(EPR) analysis 30 Chapter 3 Results and Discussion 32 3.1 Characterization of Mn oxide nanoparticles 32 3.1.1 Effect of annealing on the crystal structure of Mn oxide nanoparticles 32 3.2 Effect of crystal structure on the catalytic property 41 3.2.1 Water oxidation property of Mn oxide nanoparticles 41 3.2.2 Electrokinetics study and redox peak analysis 45 3.3 Effect of nano size on the catalytic property 57 3.3.1 Characterization of Mn5O8 materials 57 3.3.2 Catalytic activity comparison of Mn5O8 materials 64 3.3.3 Catalytic stability comparison of Mn5O8 materials 71 3.4 Electron Paramagentic Resonance (EPR) analysis 78 Chapter 4 Conclusion 84 References 86 국문초록 92Maste

Dyslipidaemia-Genotype Interactions with Nutrient Intake and Cerebro-Cardiovascular Disease

A comprehensive understanding of gene-diet interactions is necessary to establish proper dietary guidelines to prevent and manage cardio-cerebrovascular disease (CCD). We investigated the role of genetic variants associated with dyslipidaemia (DL) and their interactions with macro-nutrients for cardiovascular disease using a large-scale genome-wide association study of Korean adults. A total of 58,701 participants from a Korean genome and epidemiology study were included. Their dietary intake was assessed using a food frequency questionnaire. Dyslipidaemia was defined as total cholesterol (TCHL) ≥ 240 mg/dL, high-density lipoprotein (HDL) moderate ≥ 20%, and 20% > low in daily total energy intake (TEI); carbohydrate intake: high ≥ 60%, 60% > moderate ≥ 50%, and 50% > low; fat intake: high ≥ 40%, 40% > moderate ≥ 30%, and 30% > low. Odds ratios and 95% confidence intervals were calculated after adjusting for age; sex; body mass index (BMI); exercise status; smoking status; alcohol intake; principal component 1 (PC1); principal component 2 (PC2); and intake of carbohydrates, fats, and proteins. This analysis included 20,596 patients with dyslipidaemia and 1027 CCD patients. We found that rs2070895 related to LIPC was associated with HDL-cholesterol. Patients with the minor allele (A) in rs2070895 had a lower risk of CCD than those carrying the reference allele (G) (odds ratio [OR] = 0.8956, p-value = 1.78 × 10-2). Furthermore, individuals consuming protein below 20% TEI with the LIPC reference allele had a higher risk of CCD than those with the minor allele (interaction p-value 6.12 × 10-3). Our findings suggest that the interactions of specific polymorphisms associated with dyslipidaemia and nutrients intake can influence CCD.ope

Genome-Wide Association of New-Onset Hypertension According to Renin Concentration: The Korean Genome and Epidemiology Cohort Study

The renin-angiotensin system (RAS) is a crucial regulator of vascular resistance and blood volume in the body. This study aimed to examine the genetic predisposition of the plasma renin concentration influencing future hypertension incidence. Based on the Korean Genome and Epidemiology Cohort dataset, 5211 normotensive individuals at enrollment were observed over 12 years, categorized into the low-renin and high-renin groups. We conducted genome-wide association studies for the total, low-renin, and high-renin groups. Among the significant SNPs, the lead SNPs of each locus were focused on for further interpretation. The effect of genotypes was determined by logistic regression analysis between controls and new-onset hypertension, after adjusting for potential confounding variables. During a mean follow-up period of 7.6 years, 1704 participants (32.7%) developed hypertension. The low-renin group showed more incidence rates of new-onset hypertension (35.3%) than the high-renin group (26.5%). Among 153 SNPs in renin-related gene regions, two SNPs (rs11726091 and rs8137145) showed an association in the high-renin group, four SNPs (rs17038966, rs145286444, rs2118663, and rs12336898) in the low-renin group, and three SNPs (rs1938859, rs7968218, and rs117246401) in the total population. Most significantly, the low-renin SNP rs12336898 in the SPTAN1 gene, closely related to vascular wall remodeling, was associated with the development of hypertension (p-value = 1.3 × 10-6). We found the candidate genetic polymorphisms according to blood renin concentration. Our results might be a valuable indicator for hypertension risk prediction and preventive measure, considering renin concentration with genetic susceptibility.ope

Microalbuminuria as a simple predictor of incident diabetes over 8 years in the Korean Genome and Epidemiology Study (KoGES)

Microalbuminuria (MAU) is a common subclinical disease and related with cardiovascular outcome both in diabetic and non-diabetic patients. However, there is rare data about the effect of MAU on the development of diabetes. Thus, we aimed to investigate whether MAU is associated with the development of incident diabetes. A total of 3385 subjects without diabetes (1503 men and 1882 women; mean age, 53 years) who participated in the Ansung-Ansan cohort study from 2001-2002 (baseline) to 2011-2012 (fifth follow-up visit) were followed for a mean of 8 years. The prevalence of MAU at baseline was 10.8% (365 patients), and the incidence of newly developed diabetes during the follow-up period was 15.3% (56 patients) in subjects with MAU. The hazard ratio (HR) for development of diabetes was 1.43 (95% confidence interval (CI) 1.07-1.91, p-value 0.016), independent of traditional risk factors for diabetes including pre-diabetes, age, obesity, and family history. The impact of MAU on diabetes was also significant in the non-pre-diabetic population (HR 2.08, 95% CI 1.07-4.03, p-value 0.031). In conclusion, our results show that incident MAU is associated with future development of diabetes and could be an early marker for diabetes, even in the non-prediabetic population.ope

Predictive Value of Serum Uric Acid to HDL Cholesterol Ratio for Incident Ischemic Heart Disease in Non-Diabetic Koreans

HDL cholesterol, besides its function in lipid metabolism, plays a role in suppressing blood oxidation reactions and protecting vascular endothelial cells. The uric acid/HDL cholesterol ratio (UHR) has recently attracted attention as a new biomarker for evaluating interactions between inflammatory and anti-inflammatory substances in the blood. This study aimed to investigate the longitudinal association between UHR and incident ischemic heart disease (IHD). Data from 16,455 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korean Health Insurance Review and Assessment (HIRA) were assessed. Over 50 months after baseline enrolment, 321 (2.0%) participants developed IHD. The HRs of incident IHD were 0.85 (95% CI, 0.55-1.29), 1.42 (95% CI, 0.94-2.13), and 1.57 (95% CI, 1.01-2.45) in the second, third, and fourth UHR quartiles, respectively, after adjusting for potential confounding variables. In the subgroup analysis by sex-specific quartile, women tended to have higher HRs in the highest UHR quartile. We found that high UHR values were positively associated with incident IHD in Koreans without diabetes. An increased UHR may be a useful measure by which to assess cardiovascular risk in the preclinical stage.ope

Potential Association of Isolated γ-Glutamyltransferase Elevation with Incident Ischemic Heart Disease in Lean Koreans

Isolated elevation of γ-glutamyltransferase (GGT), a microsomal membrane-bound protein, is commonly observed in non-obese Koreans without diabetes, and its clinical implications are not well-known. Therefore, we aimed to investigate the longitudinal effect of isolated GGT on the incidence of ischemic heart disease (IHD) risk in a large cohort of lean non-diabetic Koreans. Data were obtained from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) datasets. The participants were divided into four groups according to the GGT quartile after the exclusion of those participants with diabetes, a body mass index (BMI) ≥ 25 kg/m2, alanine aminotransferase (ALT) ≥ 40 IU/L, and aspartate aminotransferase (AST)/ALT > 1.5, as well as those positive for hepatitis B surface antigen or hepatitis C antibody. We prospectively assessed the hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional hazard regression models over a 50-month period. During the follow-up period, 183 individuals (1.85%) developed IHD. After setting the lowest GGT quartile as a reference group, the HRs of IHD for GGT quartiles 2-4 were 1.66 (95% CI 0.95-2.89), 1.82 (95% CI 1.05-3.16), and 1.98 (95% CI 1.12-3.50), respectively, after adjusting for age, sex, body mass index, smoking status, alcohol consumption, physical activity, mean arterial blood pressure, fasting plasma glucose, and dyslipidemia. An isolated high GGT may be an additional measure for assessing and managing future IHD risks among lean Koreans without diabetes.ope