1.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
2.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.
3.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
4.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
5.Risk of Kawasaki Disease/Multisystem Inflammatory Syndrome Following COVID-19 Vaccination in Korean Children: A Self-Controlled Case Series Study
Suyeon KIM ; Hwa Yeon KO ; Jeongin OH ; Dongwon YOON ; Ju Hwan KIM ; Young June CHOE ; Ju-Young SHIN ; On behalf of the CoVaSC Investigators
Journal of Korean Medical Science 2025;40(3):e10-
Background:
Rare cases of Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) have been reported following the coronavirus disease 2019 (COVID-19) vaccination; however, the association between COVID-19 vaccination and the risk of developing KD/MIS-C has not yet been established.
Methods:
We conducted a self-controlled case series analysis using a large-linked database that connects the COVID-19 immunization registry with nationwide claims data. We identified individuals aged < 18 years who received their initial COVID-19 vaccination and had a KD/MIS-C diagnosis with a prescription for intravenous immunoglobulin or corticosteroids between October 18, 2021, and April 15, 2023. The observation period was set as 240 days from the date of the COVID-19 vaccination. The risk window was 60 days after vaccination, with the remaining observation period serving as the control window. The incidence rate ratios (IRRs) and 95% confidence intervals (CIs) in the risk versus control windows were estimated using the conditional Poisson regression model. We further analyzed the vaccine doses and types for secondary analysis. We also performed subgroup analyses stratified by sex, age, comorbidities, and other conditions and sensitivity analyses by varying the length of the risk window and outcome definition.
Results:
Among 2,369,490 individuals who received the COVID-19 vaccination, 12 cases of KD/MIS-C were identified, which included five and seven patients in the risk and control windows, respectively. There was no increased risk of KD/MIS-C within the 60-day period of vaccination (IRR, 0.53; 95% CI, 0.17–1.60). Secondary subgroup and sensitivity analyses showed no significant increase in the risk of KD/MIS-C after COVID-19 vaccination, which is consistent with the results of the main analysis.
Conclusion
The results of this nationwide study suggest that the risk of developing KD/MIS-C did not increase after COVID-19 vaccination. However, owing to the lack of a sufficient number of cases, future studies utilizing multinational long-term follow-up databases should be conducted. Considering the increasing incidence of KD/MIS-C and the limited understanding of its precise biological mechanisms, additional research on KD/MIS-C is warranted.
6.Rapid Recovery From SARS-CoV-2Infection Among Immunocompromised Children Despite Limited Neutralizing Antibody Response: A Virologic and Sero-Immunologic Analysis of a Single-Center Cohort
Doo Ri KIM ; Byoung Kwon PARK ; Jin Yang BAEK ; Areum SHIN ; Ji Won LEE ; Hee Young JU ; Hee Won CHO ; Keon Hee YOO ; Ki Woong SUNG ; Chae-Hong JEONG ; Tae Yeul KIM ; June-Young KOH ; Jae-Hoon KO ; Yae-Jean KIM
Journal of Korean Medical Science 2025;40(12):e52-
Background:
Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood.
Methods:
From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays.
Results:
Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed.
Conclusion
IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.
7.Risk of Kawasaki Disease/Multisystem Inflammatory Syndrome Following COVID-19 Vaccination in Korean Children: A Self-Controlled Case Series Study
Suyeon KIM ; Hwa Yeon KO ; Jeongin OH ; Dongwon YOON ; Ju Hwan KIM ; Young June CHOE ; Ju-Young SHIN ; On behalf of the CoVaSC Investigators
Journal of Korean Medical Science 2025;40(3):e10-
Background:
Rare cases of Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) have been reported following the coronavirus disease 2019 (COVID-19) vaccination; however, the association between COVID-19 vaccination and the risk of developing KD/MIS-C has not yet been established.
Methods:
We conducted a self-controlled case series analysis using a large-linked database that connects the COVID-19 immunization registry with nationwide claims data. We identified individuals aged < 18 years who received their initial COVID-19 vaccination and had a KD/MIS-C diagnosis with a prescription for intravenous immunoglobulin or corticosteroids between October 18, 2021, and April 15, 2023. The observation period was set as 240 days from the date of the COVID-19 vaccination. The risk window was 60 days after vaccination, with the remaining observation period serving as the control window. The incidence rate ratios (IRRs) and 95% confidence intervals (CIs) in the risk versus control windows were estimated using the conditional Poisson regression model. We further analyzed the vaccine doses and types for secondary analysis. We also performed subgroup analyses stratified by sex, age, comorbidities, and other conditions and sensitivity analyses by varying the length of the risk window and outcome definition.
Results:
Among 2,369,490 individuals who received the COVID-19 vaccination, 12 cases of KD/MIS-C were identified, which included five and seven patients in the risk and control windows, respectively. There was no increased risk of KD/MIS-C within the 60-day period of vaccination (IRR, 0.53; 95% CI, 0.17–1.60). Secondary subgroup and sensitivity analyses showed no significant increase in the risk of KD/MIS-C after COVID-19 vaccination, which is consistent with the results of the main analysis.
Conclusion
The results of this nationwide study suggest that the risk of developing KD/MIS-C did not increase after COVID-19 vaccination. However, owing to the lack of a sufficient number of cases, future studies utilizing multinational long-term follow-up databases should be conducted. Considering the increasing incidence of KD/MIS-C and the limited understanding of its precise biological mechanisms, additional research on KD/MIS-C is warranted.
8.Rapid Recovery From SARS-CoV-2Infection Among Immunocompromised Children Despite Limited Neutralizing Antibody Response: A Virologic and Sero-Immunologic Analysis of a Single-Center Cohort
Doo Ri KIM ; Byoung Kwon PARK ; Jin Yang BAEK ; Areum SHIN ; Ji Won LEE ; Hee Young JU ; Hee Won CHO ; Keon Hee YOO ; Ki Woong SUNG ; Chae-Hong JEONG ; Tae Yeul KIM ; June-Young KOH ; Jae-Hoon KO ; Yae-Jean KIM
Journal of Korean Medical Science 2025;40(12):e52-
Background:
Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood.
Methods:
From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays.
Results:
Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed.
Conclusion
IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.
9.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.
10.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

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