1.Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Sumin OH ; Yang-Hyun BAEK ; Sungju JUNG ; Sumin YOON ; Byeonggeun KANG ; Su-hyang HAN ; Gaeul PARK ; Je Yeong KO ; Sang-Young HAN ; Jin-Sook JEONG ; Jin-Han CHO ; Young-Hoon ROH ; Sung-Wook LEE ; Gi-Bok CHOI ; Yong Sun LEE ; Won KIM ; Rho Hyun SEONG ; Jong Hoon PARK ; Yeon-Su LEE ; Kyung Hyun YOO
Clinical and Molecular Hepatology 2024;30(2):247-262
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods:
Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results:
After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions
We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
2.Identification of Autoantigens in Pediatric Gastric Juices
Hee-Shang YOUN ; Jin-Su JUN ; Jung Sook YEOM ; Ji Sook PARK ; Jae-Young LIM ; Hyang-Ok WOO ; Jung-Wook YANG ; Seung-Chul BAIK ; Woo-Kon LEE ; Ji-Hyun SEO
Pediatric Gastroenterology, Hepatology & Nutrition 2024;27(1):15-25
Purpose:
This study aimed to investigate the presence of autoantigens in the gastric juices of children.
Methods:
Gastric juice and serum samples were obtained from 53 children <15 years of age who underwent gastric endoscopy. Among these, 8, 22, and 23 participants were in the age groups 0–5, 6–10, and 11–15 years, respectively. These samples were analyzed using two-dimensional electrophoresis (2-DE), immunoblot analysis, and matrix-assisted laser desorption ionization-time of-flight mass spectrometry. Furthermore, we reviewed the histopathological findings and urease test results and compared them with the results of 2-DE and immunoblot analysis.
Results:
There were no statistically significant differences in urease test positivity, grades of chronic gastritis, active gastritis, or Helicobacter pylori infiltration of the antrum and body among the three age groups. Three distinct patterns of gastric juice were observed on 2-DE. Pattern I was the most common, and pattern III was not observed below the age of 5 years.Histopathological findings were significantly different among active gastritis (p=0.037) and H. pylori infiltration (p=0.060) in the gastric body. The immunoblots showed large spots at an approximate pH of 3–4 and molecular weights of 31–45 kDa. These distinct, large positive spots were identified as gastric lipase and pepsin A and C.
Conclusion
Three enzymes, which are normally secreted under acidic conditions were identified as autoantigens. Further investigation of the pathophysiology and function of autoantigens in the stomach is required.
3.Effect of Xenogeneic Substances on the Glycan Profiles and Electrophysiological Properties of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Yong Guk KIM ; Jun Ho YUN ; Ji Won PARK ; Dabin SEONG ; Su-hae LEE ; Ki Dae PARK ; Hyang-Ae LEE ; Misun PARK
International Journal of Stem Cells 2023;16(3):281-292
Background and Objectives:
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold greatpromise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy.
Methods:
and Results: We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances(xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (ACTC1, TNNT2, and RYR2) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring-mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM.
Conclusions
To the best of our knowledge, this is the first study to show that the electrophysiological function andglycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.
4.Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Management of the Underlying Etiologies and Comorbidities of Heart Failure
Sang Min PARK ; Soo Youn LEE ; Mi-Hyang JUNG ; Jong-Chan YOUN ; Darae KIM ; Jae Yeong CHO ; Dong-Hyuk CHO ; Junho HYUN ; Hyun-Jai CHO ; Seong-Mi PARK ; Jin-Oh CHOI ; Wook-Jin CHUNG ; Seok-Min KANG ; Byung-Su YOO ;
Korean Circulation Journal 2023;53(7):425-451
Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, longterm anticoagulants are recommended according to the CHA 2 DS 2 -VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.
5.Additions to the Knowledge of the Fungal Order Eurotiales in Korea:Eight Undescribed Species
Thuong T. T. NGUYEN ; Ki Hyun KANG ; Dong Hee KIM ; Su Jin KIM ; Hye Yeon MUN ; Wonsu CHEON ; Hyang Burm LEE
Mycobiology 2023;51(6):417-435
Eurotiales is a relatively large order of Ascomycetes, well-known for their ability to produce secondary metabolites with potential beneficial applications. To understand their diversity and distribution, different environmental sources including soil, freshwater, insect, and indoor air were investigated. Eight strains of Eurotiales were isolated and identified based on their morphological characters and a multi-gene phylogenetic analysis of the ITS, BenA, CaM, and RPB2 regions. We identified eight taxa that were previously not reported from Korea: Aspergillus baeticus, A. griseoaurantiacus, A. spinulosporus, Penicillium anthracinoglaciei, P. labradorum, P.nalgiovense, Talaromyces atroroseus, and T. georgiensis. Detailed descriptions, illustrations, and phylogenetic tree for the eight new records species are presented, and information regarding the records is also discussed.
6.Effect of the Automatic Needle Destroyer on Healthcare Providers’ Work in an Emergency Department: A Mixed-Methods Study
Su Min KIM ; Taerim KIM ; Jee Hyang LEE ; Sun Young CHO ; Won Chul CHA
Healthcare Informatics Research 2022;28(2):123-131
Objectives:
This study introduced a novel Automatic Needle Destroyer (AND) to an emergency department (ED) and assessed its effect on healthcare providers’ work.
Methods:
Between August and September 2019, in the ED of a tertiary hospital in Seoul, we conducted a mixed-methods study to evaluate the efficiency, safety, and usability of the AND using video analysis, surveys, and in-depth interviews, wherein participants described the advantages and disadvantages of the AND.
Results:
Compared to the existing method, introducing the AND significantly reduced the operating time from 2.32 ± 1.14 seconds to 1.77 ± 3.71 seconds (p < 0.001). The normal operation rate was 90.6%. The rate of needle-stick injuries (NSIs) and the mean system usability scale (SUS) showed no significant differences. The in-depth interviews indicated that the disadvantages of the AND were mostly operational. The advantages were related to profit, reduced direct contact with hazardous waste, and behavioral changes, such as not having to recap syringes.
Conclusions
We introduced the AND to an ED environment, where NSIs occur frequently and many syringes are used, to evaluate its effect on providers’ work. The AND reduced the time for needle disposal, but the normal operation rate was low. No significant differences were found in the SUS score or the rate of NSIs. Although there are some restrictions on introducing the AND immediately, this study’s results showed its potential usefulness. Efforts to improve the operation of the device and a longer study period are needed to fully achieve safety and efficiency.
7.The Effect of Patient-Engaged Bedside Handoffs Protocol in Comprehensive Care Units
Bo Young LEE ; Kyung Jin PARK ; Jae Hyun IM ; A Reum SONG ; Mi Hyang YEON ; Hyun Ju SONG ; Do Jin JEON ; Kyu Won BAEK ; Joo Young JANG ; Su Jung CHOI
Journal of Korean Clinical Nursing Research 2022;28(3):223-232
Purpose:
The purpose of this study was to apply patient-engaged bedside handoffs in comprehensive care units, and to evaluate the effects of bedsides to nurses and patients.
Methods:
This study employed a cluster randomized cross-over design.Electrical Medical Record (EMR)-based handoffs and patient-engaged bedside handoffs were alternatively applied to 104 patients, who were assigned to a total of 30 clusters (nursing handoff teams) in 4 comprehensive care units at the S medical center in Seoul, and the patients evaluated each type of handoffs. A total of 139 nurses were also participated in the same units and evaluated each type of handoffs. Data were analyzed using t-test, Wilcoxon rank sum test, ANOVA, and Kruskal-Walls test.
Results:
The patient's satisfaction of the patient-engaged bedside handoffs was higher than that of the EMR-based handoffs (Z=-5.16, p<.001). On the other hand, the nurse's satisfaction of the patient-engaged bedside handoffs was significantly lower than that of the EMR-based handoffs (t=13.21, p<.001). There were no differences in length of the reporting time between two types of handoffs (t=-0.48, p=.634).
Conclusion
Patient satisfaction with the patient-engaged bedside handoffs was higher than that of EMR-based handoffs, and nurses' satisfaction with the patient-engaged bedside handoffs was significantly lower than that of EMR-based handoffs. Future studies are needed regarding the impacts of patient-engaged bedside handoffs on the quality of healthcare by identifying the benefits of the handoffs.
8.Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status
Chan-Hee JUNG ; Jang Won SON ; Shinae KANG ; Won Jun KIM ; Hun-Sung KIM ; Hae Soon KIM ; Mihae SEO ; Hye-Jung SHIN ; Seong-Su LEE ; Su Jin JEONG ; Yongin CHO ; Seung Jin HAN ; Hyang Mi JANG ; Mira RHO ; Shinbi LEE ; Mihyun KOO ; Been YOO ; Jung-Wha MOON ; Hye Young LEE ; Jae-Seung YUN ; Sun Young KIM ; Sung Rae KIM ; In-Kyung JEONG ; Ji-Oh MOK ; Kun Ho YOON
Diabetes & Metabolism Journal 2021;45(1):1-10
Background:
This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data.
Methods:
This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated.
Results:
In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes.
Conclusion
The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.
9.The Effects of Simultaneous Pulmonary Rehabilitation during Thoracic Radiotherapy in the Treatment of Malignant Diseases
Myeong Geun CHOI ; Hyang Yi LEE ; Si Yeol SONG ; Su Ssan KIM ; Seung Hak LEE ; Won KIM ; Chang-Min CHOI ; Sei Won LEE
Tuberculosis and Respiratory Diseases 2021;84(2):148-158
Background:
Radiotherapy is a common treatment option for lung or esophageal cancer, particularly when surgery is not feasible for patients with poor lung function. However, radiotherapy can affect pulmonary function and thereby induce pneumonitis or pneumonia, which can be fatal in patients with respiratory impairment. The purpose of this study is to evaluate if reductions in pulmonary function after radiotherapy can be minimized through simultaneous pulmonary rehabilitation (PR).
Methods:
In this matched case control study, we retrospectively analyzed patients who had undergone radiotherapy for thoracic malignant disease between January 2018 and June 2019. We analyzed results from pulmonary function tests and 6-minute walking tests (6MWT) conducted within the six months before and after radiotherapy treatment.
Results:
In total, results from 144 patients were analyzed, with 11 of the patients receiving PR and radiotherapy simultaneously. Of the 133 patients in the control group, 33 were matched with 11 patients in the PR group. Changes in forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity were significantly different between the PR group and the matched control group (240 mL vs. –10 mL, p=0.017 and 5.5% vs. 1.0%, p=0.038, respectively). The median distance of 6MWT in the PR group also increased significantly, from 407.5 m to 493.0 m after radiotherapy (p=0.017).
Conclusion
Simultaneous PR improved pulmonary function, particularly in measures of FEV1, and exercise capacity for patients with lung or esophageal cancer even after radiotherapy treatment. These findings may provide an important base of knowledge for further large population studies with long-term follow-up analysis in the identification of the PR’s effects during thoracic radiotherapy.
10.Trends in the development of human stem cell-based non-animal drug testing models
The Korean Journal of Physiology and Pharmacology 2020;24(6):441-452
In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

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