1.Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells
Hao JIN ; Yu Ran LEE ; Sungmin KIM ; Eun-Ok LEE ; Hee Kyoung JOO ; Heon Jong YOO ; Cuk-Seong KIM ; Byeong Hwa JEON
The Korean Journal of Physiology and Pharmacology 2025;29(3):293-305
The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.
2.Comparison of Natriuretic Peptide Levels in Sinus Rhythm and Atrial Fibrillation in Acute Heart Failure
Minjae YOON ; Jin Joo PARK ; Jong-Chan YOUN ; Sang Eun LEE ; Hae-Young LEE ; Jin Oh CHOI ; Kye Hun KIM ; Dong Heon YANG ; Myeong-Chan CHO ; Seok-Min KANG ; Byung-Su YOO
International Journal of Heart Failure 2025;7(2):85-95
Background and Objectives:
In chronic heart failure (HF), natriuretic peptide (NP) levels are higher in atrial fibrillation (AF) compared to sinus rhythm (SR). However, due to the loss of atrial contraction, AF patients are prone to hemodynamic decompensation at earlier stages.Since NP levels reflect disease severity, acutely decompensated AF patients may exhibit lower NP levels compared to SR patients, who retain greater hemodynamic reserve.
Methods:
We analyzed 5,048 patients with acute HF from the Korea Acute Heart Failure registry with available NP data. NP levels and echocardiographic parameters were compared between AF and SR patients. The association of NP levels with in-hospital and one-year mortality was also assessed according to cardiac rhythm.
Results:
Brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured in 2,027 and 3,021 patients, respectively. NP levels were lower in AF than in SR (median BNP, 740 vs. 1,044 pg/mL; median NT-proBNP, 4,420 vs. 5,198 pg/mL), particularly in HF with reduced or mildly reduced ejection fraction. A similar trend was observed regardless of HF onset or etiology. AF patients had smaller left ventricular (LV) end-diastolic diameter and larger left atrial size compared to SR patients. Higher NP tertiles were associated with increased in-hospital and one-year mortality in both groups.
Conclusions
In acute HF, NP levels are lower in AF than in SR. AF patients also exhibited smaller LV chamber sizes. Nevertheless, NP levels remain strong predictors of outcomes in both AF and SR patients.
3.Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells
Hao JIN ; Yu Ran LEE ; Sungmin KIM ; Eun-Ok LEE ; Hee Kyoung JOO ; Heon Jong YOO ; Cuk-Seong KIM ; Byeong Hwa JEON
The Korean Journal of Physiology and Pharmacology 2025;29(3):293-305
The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.
4.Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells
Hao JIN ; Yu Ran LEE ; Sungmin KIM ; Eun-Ok LEE ; Hee Kyoung JOO ; Heon Jong YOO ; Cuk-Seong KIM ; Byeong Hwa JEON
The Korean Journal of Physiology and Pharmacology 2025;29(3):293-305
The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.
5.Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells
Hao JIN ; Yu Ran LEE ; Sungmin KIM ; Eun-Ok LEE ; Hee Kyoung JOO ; Heon Jong YOO ; Cuk-Seong KIM ; Byeong Hwa JEON
The Korean Journal of Physiology and Pharmacology 2025;29(3):293-305
The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.
6.Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells
Hao JIN ; Yu Ran LEE ; Sungmin KIM ; Eun-Ok LEE ; Hee Kyoung JOO ; Heon Jong YOO ; Cuk-Seong KIM ; Byeong Hwa JEON
The Korean Journal of Physiology and Pharmacology 2025;29(3):293-305
The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.
7.The Clinical Outcomes of Cervical Spine Chordoma: A Nationwide Multicenter Retrospective Study
Hangeul PARK ; Yunhee CHOI ; Sungjoon LEE ; Sun-Ho LEE ; Eun-Sang KIM ; Sun Woo JANG ; Jin Hoon PARK ; Yunseong CHO ; Giwuk JANG ; Yoon HA ; Yun-Sik DHO ; Heon YOO ; Sung Uk LEE ; Seung-Ho SEO ; Ki-Jeong KIM ; Seil SOHN ; Chun Kee CHUNG
Neurospine 2024;21(3):942-953
Objective:
Chordoma, a rare malignant tumor originating from embryonal notochord remnants, exhibits high resistance to conventional treatments, making surgical resection imperative. However, the factors influencing prognosis specifically for cervical spine chordoma have not been clearly identified. We investigate the prognosis of cervical spine chordoma with factors influential in a nationwide multicenter retrospective study.
Methods:
This study included all patients diagnosed with cervical spine chordoma at 7 tertiary referral centers from January 1998 to March 2023, excluding those with clivus and thoracic spine chordomas extending into the cervical spine. Local recurrence (LR) was identified through follow-up magnetic resonance imaging, either as reappearance in completely resected tumors or regrowth in residual tumors. The study assessed LR and overall survival, analyzing factors influencing LR and death.
Results:
Forty-five patients with cervical spine chordoma had a mean age of 46.4 years. Over a median follow-up of 52 months, LR and distant metastasis were observed in 21 (46.7%) and 4 patients (8.9%), respectively, and 16 patients (36%) were confirmed dead. The 5-year and 10-year cumulative LR rates were 51.3% and 60%, respectively, while the 5-year and 10-year survival rates were 82% and 53%. Age was the only significant factor affecting mortality (hazard ratio, 1.04; 95% confidence interval, 1.04–1.07; p=0.015). Notably, the degree of resection and adjuvant therapy did not statistically significantly impact local tumor control and mortality.
Conclusion
This study, the largest multicenter retrospective analysis of cervical spine chordoma in Korea, identified age as the only factor significantly affecting patient survival.
8.The Clinical Outcomes of Cervical Spine Chordoma: A Nationwide Multicenter Retrospective Study
Hangeul PARK ; Yunhee CHOI ; Sungjoon LEE ; Sun-Ho LEE ; Eun-Sang KIM ; Sun Woo JANG ; Jin Hoon PARK ; Yunseong CHO ; Giwuk JANG ; Yoon HA ; Yun-Sik DHO ; Heon YOO ; Sung Uk LEE ; Seung-Ho SEO ; Ki-Jeong KIM ; Seil SOHN ; Chun Kee CHUNG
Neurospine 2024;21(3):942-953
Objective:
Chordoma, a rare malignant tumor originating from embryonal notochord remnants, exhibits high resistance to conventional treatments, making surgical resection imperative. However, the factors influencing prognosis specifically for cervical spine chordoma have not been clearly identified. We investigate the prognosis of cervical spine chordoma with factors influential in a nationwide multicenter retrospective study.
Methods:
This study included all patients diagnosed with cervical spine chordoma at 7 tertiary referral centers from January 1998 to March 2023, excluding those with clivus and thoracic spine chordomas extending into the cervical spine. Local recurrence (LR) was identified through follow-up magnetic resonance imaging, either as reappearance in completely resected tumors or regrowth in residual tumors. The study assessed LR and overall survival, analyzing factors influencing LR and death.
Results:
Forty-five patients with cervical spine chordoma had a mean age of 46.4 years. Over a median follow-up of 52 months, LR and distant metastasis were observed in 21 (46.7%) and 4 patients (8.9%), respectively, and 16 patients (36%) were confirmed dead. The 5-year and 10-year cumulative LR rates were 51.3% and 60%, respectively, while the 5-year and 10-year survival rates were 82% and 53%. Age was the only significant factor affecting mortality (hazard ratio, 1.04; 95% confidence interval, 1.04–1.07; p=0.015). Notably, the degree of resection and adjuvant therapy did not statistically significantly impact local tumor control and mortality.
Conclusion
This study, the largest multicenter retrospective analysis of cervical spine chordoma in Korea, identified age as the only factor significantly affecting patient survival.
9.The association between transferrin saturation and all-cause mortality in chronic kidney disease: findings from Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease
Eunmi JO ; Hyo Jin KIM ; Jayoun KIM ; Tae-Hyun YOO ; Yaeni KIM ; Soo Wan KIM ; Kook-Hwan OH ; Eun Young SEONG ; Sang Heon SONG
Kidney Research and Clinical Practice 2024;43(6):785-796
Transferrin saturation (TSAT) has been used as an indicator of iron deficiency. However, there is no consensus regarding its optimal range for patient with chronic kidney disease (CKD). We aimed to analyze the effect of TSAT on the prognosis of patients with non-dialysis CKD (NDCKD). Methods: From 2011 to 2016, 2157 NDCKD patients with baseline TSAT measurements were followed for 10 years. Patients were divided into three groups based on baseline TSAT values: <25%, ≥25% and <45%, and ≥45%. All-cause mortality and 4-point major adverse cardiovascular events (MACE) were analyzed using multivariable Cox regression analysis. Other iron biomarkers and mortality were also analyzed. Results: During a mean follow-up of 7.1 ± 2.9 years, 182 of a total of 2,157 patients (8.4%) died. Compared with the TSAT ≥25% and <45% group, the TSAT <25% group showed significantly increased all-cause mortality (hazard ratio [HR], 1.44; 95% confidence interval (CI), 1.02–2.03; p = 0.04). The occurrence of 4-point MACE was significantly increased in univariable analysis in the TSAT <25% group (HR, 1.48; 95% CI, 1.02–2.15; p = 0.04), but it was not significant in the multivariable analysis (HR, 1.38; 95% CI, 0.89–2.15; p = 0.15). Tertile comparisons of the iron-to-log-ferritin ratio showed increased mortality in the first tertile group. Conclusion: TSAT <25% is an independent risk factor for all-cause mortality in patients with NDCKD and care should be taken to prevent TSAT values of <25%. Other indicators, such as serum iron and iron-to-log-ferritin ratio, may also be used to assess iron deficiency.
10.The Third Nationwide Korean Heart Failure III Registry (KorHF III):The Study Design Paper
Minjae YOON ; Eung Ju KIM ; Seong Woo HAN ; Seong-Mi PARK ; In-Cheol KIM ; Myeong-Chan CHO ; Hyo-Suk AHN ; Mi-Seung SHIN ; Seok Jae HWANG ; Jin-Ok JEONG ; Dong Heon YANG ; Jae-Joong KIM ; Jin Oh CHOI ; Hyun-Jai CHO ; Byung-Su YOO ; Seok-Min KANG ; Dong-Ju CHOI
International Journal of Heart Failure 2024;6(2):70-75
With advancements in both pharmacologic and non-pharmacologic treatments, significant changes have occurred in heart failure (HF) management. The previous Korean HF registries, namely the Korea Heart Failure Registry (KorHF-registry) and Korean Acute Heart Failure Registry (KorAHF-registry), no longer accurately reflect contemporary acute heart failure (AHF) patients. Our objective is to assess contemporary AHF patients through a nationwide registry encompassing various aspects, such as clinical characteristics, management approaches, hospital course, and long-term outcomes of individuals hospitalized for AHF in Korea. This prospective observational multicenter cohort study (KorHF III) is organized by the Korean Society of Heart Failure. We aim to prospectively enroll 7,000 or more patients hospitalized for AHF at 47 tertiary hospitals in Korea starting from March 2018. Eligible patients exhibit signs and symptoms of HF and demonstrate either lung congestion or objective evidence of structural or functional cardiac abnormalities in echocardiography, or isolated right-sided HF. Patients will be followed up for up to 5 years after enrollment in the registry to evaluate long-term clinical outcomes. KorHF III represents the nationwide AHF registry that will elucidate the clinical characteristics, management strategies, and outcomes of contemporary AHF patients in Korea.

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