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.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
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.Development of Hydrogel Sun Patch with Wound Healing Efficacy
Da-Ye NAM ; Jin WOO ; Youngtae KIM ; JungHoon CHAE ; Young-Shin LEE ; Ji-Youl JUNG
Journal of Wound Management and Research 2025;21(1):10-17
Background:
This study focuses on the development of a hydrogel wound patch incorporating natural extracts, designed to function as a sun patch. By maintaining a moist environment and delivering bioactive compounds, the patch promotes wound healing while also providing cooling and ultraviolet (UV) protection. This dual-purpose approach enhances skin recovery and shields damaged areas from external stressors. The study aims to optimize the formulation and evaluate its efficacy for both therapeutic and cosmetic applications.
Methods:
Hydrogel solutions prepared using acrylamide, glycerol, and carboxymethyl cellulose were enriched with extracts from Saururus chinensis, Styrax japonicus, and Centella asiatica. The enriched solutions were processed into patches and tested for their adhesion, cooling effects, and UV protective abilities. Additionally, the wound healing efficacy was evaluated in a mouse model.
Results:
The hydrogel patches demonstrated comparable adhesion properties, effective skin cooling, and high UV protection rates similar to those of commercially available products. In the mouse model, the patches significantly improved wound closure and tissue regeneration in the experimental group as compared to the control group.
Conclusion
The study confirms that hydrogel sun patches enriched with natural extracts have the ability to effectively promote wound healing and offer substantial UV protection and cooling benefits, demonstrating their potential medical and cosmetic applications.
6.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
7.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.
8.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
9.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.
10.Literature analysis of tislelizumab-induced Stevens-Johnson syndrome and toxic epidermal necrolysis
Rui HAN ; Mingxi SHEN ; Hua YANG ; Zhaoshuai JI
China Pharmacy 2025;36(16):2046-2050
OBJECTIVE To analyze the clinical characteristics of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) induced by tislelizumab, providing evidence for clinical medication safety. METHODS Case reports of tislelizumab-related SJS/TEN were retrieved from CNKI, VIP, Wanfang Data, PubMed, ScienceDirect, and Embase. Descriptive analysis was performed. RESULTS Seventeen cases from 17 publications were included (SJS 4 cases, TEN 13 cases). Among them, there were 10 males and 7 females. Twelve patients were aged between 70 and 79 years. The predominant tumor type was lung cancer (10 cases). Thirteen patients received combination therapy with chemotherapeutic drugs. The median onset time of SJS/ TEN was 26 (4, 104) days. Nine patients developed SJS/TEN after the first administration of the drug. Sixteen patients exhibited prodromal rash symptoms, primarily characterized by severe skin damage such as skin detachment, accompanied by mucosal injury. Sixteen patients improved after symptomatic treatment, while one patient died. CONCLUSIONS Tislelizumab-associated SJS/TEN risk is higher in elderly patients, males, those with lung cancer and those receiving combination chemotherapy. Mucosal lesions and atypical rashes may indicate the early onset of SJS/TEN. During clinical use, pharmaceutical care can be carried out through measures such as identifying high-risk populations, closely monitoring skin symptoms from the first administration to the fifth treatment cycle, and enhancing patient education. When relevant symptoms occur, the medication should be promptly discontinued and symptomatic treatment should be administered to ensure the patient’s medication safety.

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