1.Paeoniflorin Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage by Activating Nrf2-Mediated HO-1 Signaling
Cheol PARK ; Hee-Jae CHA ; Su Hyun HONG ; Jeong Sook NOH ; Sang Hoon HONG ; Gi Young KIM ; Jung-Hyun SHIM ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):518-528
		                        		
		                        			
		                        			 Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR. 
		                        		
		                        		
		                        		
		                        	
2.Paeoniflorin Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage by Activating Nrf2-Mediated HO-1 Signaling
Cheol PARK ; Hee-Jae CHA ; Su Hyun HONG ; Jeong Sook NOH ; Sang Hoon HONG ; Gi Young KIM ; Jung-Hyun SHIM ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):518-528
		                        		
		                        			
		                        			 Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR. 
		                        		
		                        		
		                        		
		                        	
3.Paeoniflorin Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage by Activating Nrf2-Mediated HO-1 Signaling
Cheol PARK ; Hee-Jae CHA ; Su Hyun HONG ; Jeong Sook NOH ; Sang Hoon HONG ; Gi Young KIM ; Jung-Hyun SHIM ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):518-528
		                        		
		                        			
		                        			 Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR. 
		                        		
		                        		
		                        		
		                        	
4.COVID-19 Vaccination Recommendations for 2024–2025 in Korea
Wan Beom PARK ; Young Hoon HWANG ; Ki Tae KWON ; Ji Yun NOH ; Sun Hee PARK ; Joon Young SONG ; Eun Ju CHOO ; Min Joo CHOI ; Jun Yong CHOI ; Jung Yeon HEO ; Won Suk CHOI ;
Infection and Chemotherapy 2024;56(4):453-460
		                        		
		                        			
		                        			 The Korean Society of Infectious Diseases has been regularly publishing guidelines for adult immunization since 2007. Following the release of coronavirus disease 2019 (COVID-19) vaccination recommendations in 2023, significant changes have occurred due to the emergence of new variant strains and the waning immunity from previous vaccinations. This article provides a comprehensive update as of November 2024, incorporating the latest evidence and guidelines. Focusing on the 2024–2025 season, this article reviews vaccines currently authorized in Korea and assesses their effectiveness against the predominant JN.1 lineage variants. The updated recommendations prioritize high-risk groups, including adults aged 65 and older, individuals with underlying medical conditions, residents of facilities vulnerable to infection, pregnant women, and healthcare workers, for vaccination with updated vaccines targeting the JN.1 strain. Additionally, COVID-19 vaccination is available for all individuals aged 6 months and older. For most adults, a single-dose strategy is emphasized, while tailored schedules may be recommended for immunocompromised individuals. This update aims to optimize vaccination strategies in Korea to ensure comprehensive protection for high-risk populations. 
		                        		
		                        		
		                        		
		                        	
5.p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer:Gene Ontology, Machine Learning, and Drug Screening Analysis
In Ah PARK ; Yung-Kyun NOH ; Kyueng-Whan MIN ; Dong-Hoon KIM ; Jeong-Yeon LEE ; Byoung Kwan SON ; Mi Jung KWON ; Myung-Hoon HAN ; Joon Young HUR ; Jung Soo PYO
Journal of Breast Cancer 2024;27(5):305-322
		                        		
		                        			 Purpose:
		                        			A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. 
		                        		
		                        			Methods:
		                        			Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. 
		                        		
		                        			Results:
		                        			Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. 
		                        		
		                        			Conclusion
		                        			The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer. 
		                        		
		                        		
		                        		
		                        	
6.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
		                        		
		                        			
		                        			 In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs. 
		                        		
		                        		
		                        		
		                        	
7.COVID-19 Vaccination Recommendations for 2024–2025 in Korea
Wan Beom PARK ; Young Hoon HWANG ; Ki Tae KWON ; Ji Yun NOH ; Sun Hee PARK ; Joon Young SONG ; Eun Ju CHOO ; Min Joo CHOI ; Jun Yong CHOI ; Jung Yeon HEO ; Won Suk CHOI ;
Infection and Chemotherapy 2024;56(4):453-460
		                        		
		                        			
		                        			 The Korean Society of Infectious Diseases has been regularly publishing guidelines for adult immunization since 2007. Following the release of coronavirus disease 2019 (COVID-19) vaccination recommendations in 2023, significant changes have occurred due to the emergence of new variant strains and the waning immunity from previous vaccinations. This article provides a comprehensive update as of November 2024, incorporating the latest evidence and guidelines. Focusing on the 2024–2025 season, this article reviews vaccines currently authorized in Korea and assesses their effectiveness against the predominant JN.1 lineage variants. The updated recommendations prioritize high-risk groups, including adults aged 65 and older, individuals with underlying medical conditions, residents of facilities vulnerable to infection, pregnant women, and healthcare workers, for vaccination with updated vaccines targeting the JN.1 strain. Additionally, COVID-19 vaccination is available for all individuals aged 6 months and older. For most adults, a single-dose strategy is emphasized, while tailored schedules may be recommended for immunocompromised individuals. This update aims to optimize vaccination strategies in Korea to ensure comprehensive protection for high-risk populations. 
		                        		
		                        		
		                        		
		                        	
8.p27 Cell Cycle Inhibitor and Survival in Luminal-Type Breast Cancer:Gene Ontology, Machine Learning, and Drug Screening Analysis
In Ah PARK ; Yung-Kyun NOH ; Kyueng-Whan MIN ; Dong-Hoon KIM ; Jeong-Yeon LEE ; Byoung Kwan SON ; Mi Jung KWON ; Myung-Hoon HAN ; Joon Young HUR ; Jung Soo PYO
Journal of Breast Cancer 2024;27(5):305-322
		                        		
		                        			 Purpose:
		                        			A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. 
		                        		
		                        			Methods:
		                        			Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. 
		                        		
		                        			Results:
		                        			Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. 
		                        		
		                        			Conclusion
		                        			The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer. 
		                        		
		                        		
		                        		
		                        	
9.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
		                        		
		                        			
		                        			 In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs. 
		                        		
		                        		
		                        		
		                        	
10.COVID-19 Vaccination Recommendations for 2024–2025 in Korea
Wan Beom PARK ; Young Hoon HWANG ; Ki Tae KWON ; Ji Yun NOH ; Sun Hee PARK ; Joon Young SONG ; Eun Ju CHOO ; Min Joo CHOI ; Jun Yong CHOI ; Jung Yeon HEO ; Won Suk CHOI ;
Infection and Chemotherapy 2024;56(4):453-460
		                        		
		                        			
		                        			 The Korean Society of Infectious Diseases has been regularly publishing guidelines for adult immunization since 2007. Following the release of coronavirus disease 2019 (COVID-19) vaccination recommendations in 2023, significant changes have occurred due to the emergence of new variant strains and the waning immunity from previous vaccinations. This article provides a comprehensive update as of November 2024, incorporating the latest evidence and guidelines. Focusing on the 2024–2025 season, this article reviews vaccines currently authorized in Korea and assesses their effectiveness against the predominant JN.1 lineage variants. The updated recommendations prioritize high-risk groups, including adults aged 65 and older, individuals with underlying medical conditions, residents of facilities vulnerable to infection, pregnant women, and healthcare workers, for vaccination with updated vaccines targeting the JN.1 strain. Additionally, COVID-19 vaccination is available for all individuals aged 6 months and older. For most adults, a single-dose strategy is emphasized, while tailored schedules may be recommended for immunocompromised individuals. This update aims to optimize vaccination strategies in Korea to ensure comprehensive protection for high-risk populations. 
		                        		
		                        		
		                        		
		                        	
            
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