1.Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300–CD38 Axis
Ji-Hye SONG ; Hyo-Jin KIM ; Jangho LEE ; Seung-Pyo HONG ; Min-Yu CHUNG ; Yu-Geun LEE ; Jae Ho PARK ; Hyo-Kyoung CHOI ; Jin-Taek HWANG
Biomolecules & Therapeutics 2024;32(2):214-223
Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values.CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression.The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300–CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.
2.Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor
Chun-Bong SYNN ; Dong Kwon KIM ; Jae Hwan KIM ; Youngseon BYEON ; Young Seob KIM ; Mi Ran YUN ; Ji Min LEE ; Wongeun LEE ; Eun Ji LEE ; Seul LEE ; You-Won LEE ; Doo Jae LEE ; Hyun-Woo KIM ; Chang Gon KIM ; Min Hee HONG ; June Dong PARK ; Sun Min LIM ; Kyoung-Ho PYO
Yonsei Medical Journal 2022;63(1):42-55
Purpose:
Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer.
Materials and Methods:
The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell.
Results:
We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA.
Conclusion
The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.
3.Effects of Virtual Reality-Based Cognitive Training in the Elderly with and without Mild Cognitive Impairment
Seri MAENG ; Jin Pyo HONG ; Won-Hyoung KIM ; Hyeyoung KIM ; Seo-Eun CHO ; Jae Myeong KANG ; Kyoung-Sae NA ; Seok-Hee OH ; Jung Woon PARK ; Jae Nam BAE ; Seong-Jin CHO
Psychiatry Investigation 2021;18(7):619-627
Objective:
This study aimed to introduce a 4-week long fully immersive virtual reality-based cognitive training (VRCT) program that could be applied for both a cognitively normal elderly population and patients with mild cognitive impairment (MCI). In addition, we attempted to investigate the neuropsychological effects of the VRCT program in each group.
Methods:
A total of 56 participants, 31 in the MCI group and 25 in the cognitively normal elderly group, underwent eight sessions of VRCT for 4 weeks. In order to evaluate the effects of the VRCT, the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet was administered before and after the program. The program’ s safety was assessed using a simulator sickness questionnaire (SSQ), and availability was assessed using the presence questionnaire.
Results:
After the eighth session of the VRCT program, cognitive improvement was observed in the ability to learn new information, visuospatial constructional ability, and frontal lobe function in both groups. At the baseline evaluation, based on the SSQ, the MCI group complained of disorientation and nausea significantly more than the cognitively normal elderly group did. However, both groups showed a reduction in discomfort as the VRCT program progressed.
Conclusion
We conclude that our VRCT program helps improve cognition in both the MCI group and cognitively normal elderly group. Therefore, the VRCT is expected to help improve cognitive function in elderly populations with and without MCI.
4.Effects of Virtual Reality-Based Cognitive Training in the Elderly with and without Mild Cognitive Impairment
Seri MAENG ; Jin Pyo HONG ; Won-Hyoung KIM ; Hyeyoung KIM ; Seo-Eun CHO ; Jae Myeong KANG ; Kyoung-Sae NA ; Seok-Hee OH ; Jung Woon PARK ; Jae Nam BAE ; Seong-Jin CHO
Psychiatry Investigation 2021;18(7):619-627
Objective:
This study aimed to introduce a 4-week long fully immersive virtual reality-based cognitive training (VRCT) program that could be applied for both a cognitively normal elderly population and patients with mild cognitive impairment (MCI). In addition, we attempted to investigate the neuropsychological effects of the VRCT program in each group.
Methods:
A total of 56 participants, 31 in the MCI group and 25 in the cognitively normal elderly group, underwent eight sessions of VRCT for 4 weeks. In order to evaluate the effects of the VRCT, the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet was administered before and after the program. The program’ s safety was assessed using a simulator sickness questionnaire (SSQ), and availability was assessed using the presence questionnaire.
Results:
After the eighth session of the VRCT program, cognitive improvement was observed in the ability to learn new information, visuospatial constructional ability, and frontal lobe function in both groups. At the baseline evaluation, based on the SSQ, the MCI group complained of disorientation and nausea significantly more than the cognitively normal elderly group did. However, both groups showed a reduction in discomfort as the VRCT program progressed.
Conclusion
We conclude that our VRCT program helps improve cognition in both the MCI group and cognitively normal elderly group. Therefore, the VRCT is expected to help improve cognitive function in elderly populations with and without MCI.
5.Analytical Quality by Design Methodology Approach for Simultaneous Quantitation of Paeoniflorin and Decursin in Herbal Medicine by RP-HPLC Analysis
Min Kyoung KIM ; Geonha PARK ; Seon-Pyo HONG ; Young Pyo JANG
Natural Product Sciences 2021;27(4):264-273
Simultaneous quantification of multiple marker compounds in herbal medicine by high performance liquid chromatography (HPLC) analysis is still a challenge due to the complexity in various parameters to be considered and co-existing multi-components. As a case study, a reliable HPLC method for simultaneous quantification of paeoniflorin from Paeoniae Radix and decursin from Angelicae Gigantis Radix in various commercial herbal medicine was developed based on analytical quality by design (AQbD) strategy. As a first step, risk assessment was performed to select the critical method parameters (CMPs) which were decided as organic mobile phase ratio and column oven temperature. In order to evaluate the effect of the CMPs on critical method attributes (CMAs) of peak resolution and tailing, central composite design (CCD) was employed. The final chromatographic conditions were optimized as follows: column- C 18 , 4.6 × 250 mm, 5 μm particle size; mobile phase- A: acetonitrile, B: 0.1% acetic acid water; detection wavelength- 235 nm for paeoniflorin, 325 nm for decursin; column oven temperature- 25 o C; flow rate- 1.0 mL/min; gradient mobile phase system as Time (min) : % A, 0:14, 25:14, 30:50, 60:50, 61:100, 65:100, 66:14, 75:14. The method was successfully validated according to the International Conference on Harmonization (ICH) guidelines and piloted for ten commercial herbal medicines.
6.Modification and Validation of a Complaint-Oriented Emergency Department Triage System:A Multicenter Observational Study
Dong Hyun CHOI ; Won Pyo HONG ; Kyoung Jun SONG ; Tae Han KIM ; Sang Do SHIN ; Ki Jeong HONG ; Jeong Ho PARK ; Joo JEONG
Yonsei Medical Journal 2021;62(12):1145-1154
Purpose:
The objective of this study was to modify and validate an emergency department (ED) triage system with improved prediction performance on hospital outcomes by modifying the Korean Triage and Acuity Scale (KTAS).
Materials and Methods:
We performed a retrospective observational study at three academic universities in South Korea. The KTAS code, determined by the chief complaint and the selected modifier of a patient, was used to derive the Modified KTAS (MKTAS). We calculated the area under the receiver operating characteristics curve (AUC) and the test characteristics to evaluate the performance of MKTAS to predict hospital mortality, critical outcome, and admission.
Results:
A total of 272402 and 128831 ED visits were used for the derivation and validation of MKTAS, respectively. Compared to KTAS, MKTAS had significantly higher AUC values for the prediction of hospital mortality [MKTAS 0.826 (0.818–0.835) vs. KTAS 0.794 (0.784–0.803)], critical outcome [MKTAS 0.836 (0.830–0.841) vs. 0.798 (0.792–0.804)], and admission [MKTAS 0.725 (0.723– 0.728) vs. KTAS 0.685 (0.682–0.688)]. The sensitivity for predicting hospital mortality and critical outcome, as well as the specificity for predicting admission, were significantly improved.
Conclusion
MKTAS was derived by modifying the KTAS, and then validated. Compared with KTAS, MKTAS showed better discriminating ability to predict hospital outcomes. Continuous efforts to evaluate and modify widely used triage systems are required to improve their performance.
7.Prevalence of DSM-IV Major Psychiatric Disorders among North Korean Defectors in South Korea
Kyoung Eun LEE ; Carolyn Seungyoun MOON ; Ji Hyun AN ; Hyo Chul LEE ; Da Eun KIM ; Subin PARK ; Minji LEE ; Hye In CHANG ; Jin Pyo HONG
Psychiatry Investigation 2020;17(6):541-546
Objective:
The aim of this study was to estimate the prevalence of major psychiatric disorders among North Korean defectors (NKD) settled in South Korea.
Methods:
The study population consisted of 294 North Korean defectors, aged 18 to 64 years settled in South Korea for 3 years or less. Between June 1, 2016 and October 31, 2016, face-to-face interviews were conducted using the North Korean version of the WHO-Composite International Diagnostic Interview (NK-CIDI) to diagnose DSM-IV psychiatric disorders.
Results:
The lifetime prevalence of any DSM-IV psychiatric disorders was 62.2% in NKD and 25.0% in the general Korean population. The prevalence of specific disorders in NKD and general Korean population was as follows: 22.3% and 4.9% for major depressive disorder (MDD), 12.2% and 1.4% for post-traumatic stress disorder (PTSD), 18.0% and 4.8% for nicotine dependence, and 14.5% and 11.2% for alcohol abuse. The incidence of every single psychiatric disorder varied in each country. For instance, the generalized anxiety disorder, specific phobia, and alcohol use disorder occurred more frequently in North Korea whereas PTSD was more prevalent in other countries.
Conclusion
The prevalence of psychiatric disorders among NKD was quite higher than in the general population of South Korea.
8.Huge Intramural Duodenal Hematoma Complicated with Obstructive Jaundice following Endoscopic Hemostasis.
Hak Su KIM ; Hee Kyoung KIM ; Won Hee KIM ; Sung Pyo HONG ; Joo Young CHO
The Korean Journal of Gastroenterology 2019;73(1):39-44
Intramural hematoma of the duodenum is a relatively unusual complication associated with the endoscopic treatment of bleeding peptic ulcers. Intramural hematomas are typically resolved spontaneously with conservative treatment alone. We report a case of an intramural duodenal hematoma following endoscopic hemostasis with epinephrine injection therapy, which was associated with transient obstructive jaundice in a patient undergoing hemodialysis. The patient developed biliary sepsis due to obstruction of the common bile duct secondary to the huge hematoma. He was treated with fluoroscopy-guided drainage catheter insertion, which spontaneously resolved the biliary sepsis through conservative treatment in 6 weeks. Fluoroscopy-guided drainage may impact the treatment of intramural hematomas that involve life-threatening complications.
Catheters
;
Cholestasis
;
Common Bile Duct
;
Drainage
;
Duodenal Ulcer
;
Duodenum
;
Epinephrine
;
Hematoma*
;
Hemorrhage
;
Hemostasis, Endoscopic*
;
Humans
;
Jaundice, Obstructive*
;
Peptic Ulcer
;
Renal Dialysis
;
Sepsis
9.The Bodily Panic Symptoms and Predisposing Stressors in Korean Patients with Panic Disorder
Hyun Joo LEE ; Min Sook GIM ; Se Joo KIM ; Seon Cheol PARK ; Jong Chul YANG ; Kyoung Uk LEE ; Sang Hyuk LEE ; Seung Jae LEE ; Se Won LIM ; Jeong Ho CHAE ; Sang Woo HAN ; Jin Pyo HONG ; Ho Jun SEO
Journal of Korean Neuropsychiatric Association 2019;58(4):339-345
OBJECTIVES:
The purpose of this study was to investigate the distinctive features of bodily panic symptoms and the predisposing conditions in Korean patients with panic disorder.
METHODS:
This was a retrospective chart review study and the data were collected from twelve university-affiliated hospitals in Korea. The patients selected met the diagnostic criteria for panic disorder, were older than 20 years of age, and had initially visited a psychiatry department. The assessments included the chief complaints related to bodily panic symptoms, recent stressors, recent history of alcohol and sleep problems, and time to visit an outpatient clinic.
RESULTS:
A total of 814 participants were included in the study. The most commonly experienced symptoms were cardiovascular and respiratory symptoms, which were observed in 63.9% and 55.4% of participants, respectively. Just before the onset of a panic attack, 25.6% of participants experienced sleep-related problems. Episodic binge drinking was also frequently observed (13.2%) and was more prevalent in men than in women (22.6% vs. 4.9%, p<0.001). About 75% of participants experienced stressful life events just before panic onset. Work-related issues were more prevalent in men than in women (22.0% vs. 13.4%, p=0.001). Family-related issues (4.8% vs. 14.1%, p<0.001) and conflict with a spouse or partner (4.0% vs.11.7%, p<0.001) were more prominent in women than in men.
CONCLUSION
Our results suggest that cardiovascular symptoms are the most common bodily panic symptoms in Korean patients. Our results suggest that a substantial portion of the Korean patients experienced stressful life events, sleep problems, and/or episodic binge drinking just before the onset of panic disorder.
10.Prevalence and Correlates of Suicidal Thoughts and Behaviors among North Korean Defectors.
Ji Hyun AN ; Kyoung Eun LEE ; Hyo Chul LEE ; Hae Soo KIM ; Jin Yong JUN ; Hye In CHANG ; Suk Sun KIM ; Su Yeon LEE-TAULER ; Jin Pyo HONG
Psychiatry Investigation 2018;15(5):445-451
OBJECTIVE: Despite the increasing number of North Korean defectors, research on their mental health conditions and suicidal thoughts and behaviors has not been conducted systematically. We examined the prevalence and risk factors of suicidal thoughts and behaviors in North Korean defectors. METHODS: This study focused on 300 North Korean defectors recruited from regional resettlement centers in South Korea. In-person interviews based on the North Korean version of the Composite International Diagnostic Interview were conducted to diagnose mental disorders and assess suicidal thoughts and behaviors. Logistic regression analyses were performed to evaluate the association between suicidal thoughts and behaviors and socio-demographic variables, and DSM-IV mental disorders. RESULTS: Lifetime prevalence of suicidal ideation, plans, and attempts were 28.3, 13.3, and 17.3%, respectively. Female sex (OR: 2.0, 95% CI: 1.0–3.9), presence of health problems in the past year (2.6, 95% CI: 1.4–4.6), and absence of both South Korean acquaintances (1.9, 95% CI: 1.0–3.4) and North Korean family (1.7, 95% CI: 1.0–2.9) were associated with higher odds of suicidal thoughts and behaviors, after adjusting for participant age, sex, and education. Presence of a mental disorder was associated with a significantly increased odd of suicide ideation, plan, and attempt. Of all mental disorder categories, agoraphobia had the strongest association with suicidal ideation (6.5, 95% CI: 2.0–21.6), plans (7.7, 95% CI: 2.5–23.2) and attempts (12.0, 95% CI: 3.5–40.8). CONCLUSION: Suicidal thoughts and behaviors among North Korean defectors are higher than the general population in South Korea, especially show high rates in transit countries. Further study should focus on the changes in suicidal thoughts and behaviors according to the settlement process and early prevention.
Agoraphobia
;
Diagnostic and Statistical Manual of Mental Disorders
;
Education
;
Female
;
Friends
;
Humans
;
Korea
;
Logistic Models
;
Mental Disorders
;
Mental Health
;
Prevalence*
;
Risk Factors
;
Suicidal Ideation
;
Suicide

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