1.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
2.Apurinic/apyrimidinic endonuclease 1 is associated with poor prognosis after curative resection followed by adjuvant chemotherapy in patients with stage III colon cancer
Ji Hyeong SONG ; Myung Sun LEE ; Eun Young CHA ; Kyung Ha LEE ; Ji Yeon KIM ; Jin Soo KIM
Korean Journal of Clinical Oncology 2022;18(1):1-10
Purpose:
Apurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme involved in the base excision repair pathway. It also has redox activity and maintains various transcription factors in an active reduced state. APE1 may be associated with chemoresistance. In the present study, we first investigated the expression level of APE1 protein and its correlation with oncologic outcomes of oxaliplatin-based chemotherapy in patients with stage III colon cancer. Further, we investigated the effects of human APE1 siRNA on the sensitivity of oxaliplatin in SNU-C2A colon cancer cells.
Methods:
Tissue specimens from tumor and normal colon of 33 patients with stage III colon cancer were obtained from 2006 to 2009. The patients received at least eight cycles of oxaliplatin-based chemotherapy. APE1 expression was analyzed by immunohistochemistry and Western blotting using a cultured SNU-C2A cell line. Cell viability and apoptosis were determined by Cell Counting Kit-8 and caspase-3 cleavage using Western blotting.
Results:
All the colon cancer tissues showed APE1 staining in the nucleus, whereas all the normal colon tissues were negative for APE1 staining in the cytoplasm. The group with a higher expression of APE1 demonstrated poorer prognosis than the group with low expression (P=0.026 for overall survival and P=0.021 for disease-free survival). Treatment with oxaliplatin resulted in a dose-dependent increase in APE1 expression in SNU-C2A cells. APE1 siRNA significantly enhanced oxaliplatin-induced growth inhibition, and also increased oxaliplatin-induced apoptosis in SNU-C2A cells.
Conclusion
APE1 could be considered a prognostic factor in colon cancer patients treated with oxaliplatin-based chemotherapy.
3.Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Ji Eun JUN ; In Kyung JEONG ; Jae Myung YU ; Sung Rae KIM ; In Kye LEE ; Kyung Ah HAN ; Sung Hee CHOI ; Soo Kyung KIM ; Hyeong Kyu PARK ; Ji Oh MOK ; Yong ho LEE ; Hyuk Sang KWON ; So Hun KIM ; Ho Cheol KANG ; Sang Ah LEE ; Chang Beom LEE ; Kyung Mook CHOI ; Sung Ho HER ; Won Yong SHIN ; Mi Seung SHIN ; Hyo Suk AHN ; Seung Ho KANG ; Jin Man CHO ; Sang Ho JO ; Tae Joon CHA ; Seok Yeon KIM ; Kyung Heon WON ; Dong Bin KIM ; Jae Hyuk LEE ; Moon Kyu LEE
Diabetes & Metabolism Journal 2020;44(1):78-90
BACKGROUND:
Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.
METHODS:
This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.
RESULTS:
After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.
CONCLUSION
The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.
4.Evaluation of dietary habits according to breakfast consumption in Korean adolescents: based on the 6(th) Korea National Health and Nutrition Examination Survey, 2013 ~ 2015
Hyun Suk KIM ; Ui Suk LEE ; Seon Hyeong KIM ; Youn Soo CHA
Journal of Nutrition and Health 2019;52(2):217-226
PURPOSE: This study examined the nutrient intake and dietary habits based on breakfast consumption in Korean adolescents. METHODS: The data of the 2013 ~ 2015 Korea National Health and Nutrition Examination Survey (KNHANES) were used in this study. The analysis included 1,281 adolescents aged 12 to 18 years. The subjects were divided into two groups (EBF: eating breakfast, n = 911; SBF: skipping breakfast, n = 370). RESULTS: The EBF group was significantly younger than the SBF group. In addition, the EBF group had a significantly lower frequency of skipping dinner than the SBF group. The EBF group consumed significantly higher levels of most nutrients except for vitamin A than the SBF group. The percent of nutrient intake under the EAR (estimated average requirements) in the EBF group were also significantly lower than that in the SBF group. Moreover, the NAR (nutrient adequacy ratio) and MAR (mean adequacy ratio) of the EBF group were significantly higher than those of the SBP group. The intake of cereal, sugars and sweeteners, vegetables, and eggs in the EBF group was significantly higher than that in the SBF group. CONCLUSION: The habit of skipping breakfast in adolescents leads to a decrease in the total nutrient intake and imbalanced dietary habits. Breakfast consumption in adolescence is very important. Therefore, more studies will be needed to develop nutrition education systematically in Korean adolescents.
Adolescent
;
Breakfast
;
Carbohydrates
;
Ear
;
Eating
;
Edible Grain
;
Education
;
Eggs
;
Food Habits
;
Humans
;
Korea
;
Meals
;
Nutrition Surveys
;
Ovum
;
Sweetening Agents
;
Vegetables
;
Vitamin A
5.The Association between Suicidal Ideation, Anxiety, and Sleep Quality Among College Students in a City.
Shin Hyeong KIM ; Chul Soo PARK ; Bong Jo KIM ; Cheol Soon LEE ; Boseok CHA ; Dongyun LEE ; Ji Yeong SEO ; Jae Won CHOI ; In Young AHN ; So Jin LEE
Sleep Medicine and Psychophysiology 2017;24(1):55-61
OBJECTIVES: Suicide is one of the leading causes of death among young adults. We investigated whether anxiety level and sleep quality were related to suicide ideation among university students. METHODS: Questionnaires were distributed to 1094 students at a local college. The scale for suicide Ideation, the Hospital Anxiety-Depression scale, the Pittsburgh Sleep Quality Index, and Morningness-eveningness questionnaires were used. Multiple linear regression analysis was conducted to examine the relationship between these variables and suicide ideation. RESULTS: Among the 292 students who answered the suicide ideation questionnaire, 31 students had a high suicide ideation score and 261 patients had a low suicide ideation score. Demographic variables that showed significant differences between the two groups were gender, exercise, chronotype, sleep quality, depression and anxiety. The results of multiple linear regression analysis showed that suicidal ideation increased as the level of sleep quality decreased. There was no significant relationship between depression and suicidal ideation. Another multiple linear regression analysis was performed to evaluate the relationship between sleep quality sleep related factors. This suggested the quality of sleep decreased as weekend oversleep increased. CONCLUSION: The results of this study showed that when anxiety was higher and the quality of sleep was lower, the more suicide ideation increased. Therefore, improving sleep quality and reducing anxiety are important strategies for reducing suicidal ideation.
Anxiety*
;
Cause of Death
;
Depression
;
Humans
;
Linear Models
;
Suicidal Ideation*
;
Suicide
;
Young Adult
6.Characterization of Echinostoma cinetorchis endoribonuclease, RNase H.
Sung Bin LIM ; Seok Ho CHA ; Seung JEGAL ; Hojong JUN ; Seo Hye PARK ; Bo Young JEON ; Jhang Ho PAK ; Young Yil BAKH ; Tong Soo KIM ; Hyeong Woo LEE
The Korean Journal of Parasitology 2017;55(4):451-455
Echinostoma cinetorchis is an oriental intestinal fluke causing significant pathological damage to the small intestine. The aim of this study was to determine a full-length cDNA sequence of E. cinetorchis endoribonuclease (RNase H; EcRNH) and to elucidate its molecular biological characters. EcRNH consisted of 308 amino acids and showed low similarity to endoribonucleases of other parasites (<40%). EcRNH had an active site centered on a putative DDEED motif instead of DEDD conserved in other species. A recombinant EcRNH produced as a soluble form in Escherichia coli showed enzymatic activity to cleave the 3′-O-P bond of RNA in a DNA-RNA duplex, producing 3′-hydroxyl and 5′-phosphate. These findings may contribute to develop antisense oligonucleotides which could damage echinostomes and other flukes.
Amino Acids
;
Catalytic Domain
;
DNA, Complementary
;
Echinostoma*
;
Endoribonucleases
;
Escherichia coli
;
Intestine, Small
;
Oligonucleotides, Antisense
;
Parasites
;
Ribonuclease H*
;
Ribonucleases*
;
RNA
;
Trematoda
7.Maternal antimullerian hormone as a predictor of fetal aneuploidy occurring in an early pregnancy loss.
So Hyun SHIM ; Hyeong In HA ; Yong Wook JUNG ; Sung Shin SHIM ; Yeon Kyung CHO ; Ji Youn KIM ; Kyoung Jin LEE ; Dong Hyun CHA ; Soo Hyun KIM ; Hee Jin PARK
Obstetrics & Gynecology Science 2015;58(6):494-500
OBJECTIVE: The purpose of the study was to examine the relationship between the parameter representing ovarian reserve and the fetal aneuploidy in early spontaneous miscarriage. METHODS: A multicenter retrospective cohort study was performed in patients who were diagnosed with early pregnancy loss (< or =13 gestational weeks) and examined for fetal karyotype at the CHA Gangnam Medical Center, CHA Bundang Medical Center, and CHA Gumi Medical Center between January 2011 and December 2012. Karyotyping was performed by the Genetic Laboratory of the Fertility Center of CHA Gangnam Medical Center. Medical records were reviewed for demographics, karyotype analysis and hormonal assay of ovarian reserve including antimullerian hormone (AMH) and follicle stimulating hormone. Statistical analysis was performed using SPSS software. RESULTS: A total 462 patients were included in this study. The mean age of the patients was 35.31+/-4.12 years and the mean AMH level was 3.88+/-3.50 ng/mL (n=195). Two hundred eleven conceptuses (45.7%) of patients showed the euploid and 251 (54.3%) showed the aneuploid. There are significant differences in maternal age, AMH and gestational age between fetal euploid and aneuploid groups (34.46+/-4.35 vs. 36.04+/-3.78 years, P<0.001; 4.60+/-3.86 vs. 3.43+/-3.18 ng/mL, P=0.022; 7.67+/-1.54 vs. 8.27+/-1.46 weeks, P<0.001, respectively). Multivariate analysis revealed that low AMH level and early gestational age were maternal age-independent markers for fetal aneuploid (P<0.001 and P=0.045, respectively). CONCLUSION: Low maternal AMH level might be a predicting marker for fetal aneuploid in early pregnancy loss.
Abortion, Spontaneous
;
Aneuploidy*
;
Anti-Mullerian Hormone*
;
Chromosome Aberrations
;
Cohort Studies
;
Demography
;
Female
;
Fertility
;
Follicle Stimulating Hormone
;
Gestational Age
;
Gyeongsangbuk-do
;
Humans
;
Karyotype
;
Karyotyping
;
Maternal Age
;
Medical Records
;
Multivariate Analysis
;
Pregnancy*
;
Retrospective Studies
8.Lifespan Extending and Stress Resistant Properties of Vitexin from Vigna angularis in Caenorhabditis elegans.
Eun Byeol LEE ; Jun Hyeong KIM ; Youn Soo CHA ; Mina KIM ; Seuk Bo SONG ; Dong Seok CHA ; Hoon JEON ; Jae Soon EUN ; Sooncheon HAN ; Dae Keun KIM
Biomolecules & Therapeutics 2015;23(6):582-589
Several theories emphasize that aging is closely related to oxidative stress and disease. The formation of excess ROS can lead to DNA damage and the acceleration of aging. Vigna angularis is one of the important medicinal plants in Korea. We isolated vitexin from V. angularis and elucidated the lifespan-extending effect of vitexin using the Caenorhabditis elegans model system. Vitexin showed potent lifespan extensive activity and it elevated the survival rates of nematodes against the stressful environments including heat and oxidative conditions. In addition, our results showed that vitexin was able to elevate antioxidant enzyme activities of worms and reduce intracellular ROS accumulation in a dose-dependent manner. These studies demonstrated that the increased stress tolerance of vitexin-mediated nematode could be attributed to increased expressions of stress resistance proteins such as superoxide dismutase (SOD-3) and heat shock protein (HSP-16.2). In this work, we also studied whether vitexin-mediated longevity activity was associated with aging-related factors such as progeny, food intake, growth and movement. The data revealed that these factors were not affected by vitexin treatment except movement. Vitexin treatment improved the body movement of aged nematode, suggesting vitexin affects healthspan as well as lifespan of nematode. These results suggest that vitexin might be a probable candidate which could extend the human lifespan.
Acceleration
;
Aging
;
Caenorhabditis elegans*
;
Caenorhabditis*
;
DNA Damage
;
Eating
;
Heat-Shock Proteins
;
Hot Temperature
;
Humans
;
Korea
;
Longevity
;
Oxidative Stress
;
Plants, Medicinal
;
Superoxide Dismutase
;
Survival Rate
9.Seroprevalence of Plasmodium vivax in the Republic of Korea (2003-2005) using Indirect Fluorescent Antibody Test.
Tong Soo KIM ; Yoon Joong KANG ; Won Ja LEE ; Byoung Kuk NA ; Sung Ung MOON ; Seok Ho CHA ; Sung Keun LEE ; Yun Kyu PARK ; Jhang Ho PAK ; Pyo Yun CHO ; Youngjoo SOHN ; Hyeong Woo LEE
The Korean Journal of Parasitology 2014;52(1):1-7
Plasmodium vivax reemerged in the Republic of Korea (ROK) in 1993, and is likely to continue to affect public health. The purpose of this study was to measure levels of anti-P. vivax antibodies using indirect fluorescent antibody test (IFAT) in border areas of ROK, to determine the seroprevalence of malaria (2003-2005) and to plan effective control strategies. Blood samples of the inhabitants in Gimpo-si, Paju-si, and Yeoncheon-gun (Gyeonggi-do), and Cheorwon-gun (Gangwon-do) were collected and kept in Korea Centers for Disease Control and Prevention (KCDC). Out of a total of 1,774 serum samples tested, the overall seropositivity was 0.94% (n=17). The seropositivity was the highest in Paju-si (1.9%, 7/372), followed by Gimpo-si (1.4%, 6/425), Yeoncheon-gun (0.67%, 3/451), and Cheorwon-gun (0.19%, 1/526). The annual parasite incidence (API) in these areas gradually decreased from 2003 to 2005 (1.69, 1.09, and 0.80 in 2003, 2004, and 2005, respectively). The highest API was found in Yeoncheon-gun, followed by Cheorwon-gun, Paju-si, and Gimpo-si. The API ranking in these areas did not change over the 3 years. The seropositivity of Gimpo-si showed a strong linear relationship with the API of 2005 (r=0.9983, P=0.036). Seropositivity data obtained using IFAT may be useful for understanding malaria prevalence of relevant years, predicting future transmission of malaria, and for establishing and evaluating malaria control programs in affected areas.
Antibodies, Protozoan/*blood
;
Fluorescent Antibody Technique, Indirect
;
Humans
;
Incidence
;
Malaria, Vivax/*epidemiology
;
Plasmodium vivax/*immunology
;
Republic of Korea/epidemiology
;
Seroepidemiologic Studies
10.Enhancing effects of serum-rich and cytokine-supplemented culture conditions on developing blastocysts and deriving porcine parthenogenetic embryonic stem cells.
Soo Kyung JUNG ; Hyun Jung KIM ; Chan Lan KIM ; Joo Hyeong LEE ; Jin Young YOU ; Eun Song LEE ; Jeong Mook LIM ; Seon Jong YUN ; Jae Young SONG ; Sang Ho CHA
Journal of Veterinary Science 2014;15(4):519-528
The present study was conducted to develop an effective method for establishment of porcine parthenogenetic embryonic stem cells (ppESCs) from parthenogenetically activated oocyte-derived blastocysts. The addition of 10% fetal bovine serum (FBS) to the medium on the 3rd day of oocyte culturing improved the development of blastocysts, attachment of inner cell masses (ICMs) onto feeder cells, and formation of primitive ppESC colonies. ICM attachment was further enhanced by basic fibroblast growth factor, stem cell factor, and leukemia inhibitory factor. From these attached ICMs, seven ppESC lines were established. ppESC pluripotency was verified by strong enzymatic alkaline phosphatase activity and the expression of pluripotent markers OCT3/4, Nanog, and SSEA4. Moreover, the ppESCs were induced to form an embryoid body and teratoma. Differentiation into three germ layers (ectoderm, mesoderm, and endoderm) was confirmed by the expression of specific markers for the layers and histological analysis. In conclusion, data from the present study suggested that our modified culture conditions using FBS and cytokines are highly useful for improving the generation of pluripotent ppESCs.
Animals
;
Blastocyst/*cytology
;
Cell Culture Techniques/*veterinary
;
*Cell Differentiation
;
Cytokines/metabolism
;
Embryonic Stem Cells/*cytology
;
Parthenogenesis
;
Pluripotent Stem Cells/*cytology
;
Swine/*physiology

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