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.Effect of remimazolam on intraoperative hemodynamic stability in patients undergoing cerebrovascular bypass surgery: a prospective randomized controlled trial
Chang-Hoon KOO ; Si Un LEE ; Hyeong-Geun KIM ; Soowon LEE ; Yu Kyung BAE ; Ah-Young OH ; Young-Tae JEON ; Jung-Hee RYU
Korean Journal of Anesthesiology 2025;78(2):148-158
Background:
Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery.
Methods:
Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil.
Results:
Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group.
Conclusions
Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.
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.Effect of remimazolam on intraoperative hemodynamic stability in patients undergoing cerebrovascular bypass surgery: a prospective randomized controlled trial
Chang-Hoon KOO ; Si Un LEE ; Hyeong-Geun KIM ; Soowon LEE ; Yu Kyung BAE ; Ah-Young OH ; Young-Tae JEON ; Jung-Hee RYU
Korean Journal of Anesthesiology 2025;78(2):148-158
Background:
Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery.
Methods:
Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil.
Results:
Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group.
Conclusions
Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.
6.Triglyceride-glucose parameters as predictors of diabetes mellitus incidence in Korean adults: a secondary analysis of a Prospective Cohort Study
Yu Jin PARK ; Miseon SHIN ; Hyun Seon JEON ; Eun Hee YANG
Journal of Korean Academy of Nursing 2025;55(2):205-221
Purpose:
This study aimed to evaluate the association between triglyceride-glucose (TyG)–related parameters and the incidence of diabetes mellitus in Korean adults. Data were obtained from the Korean Genome and Epidemiology Study (KoGES).
Methods:
This secondary analysis examined data from 6,816 adults aged 40–69 years who participated in the KoGES from 2001 to 2020. TyG–related parameters, including the TyG index, TyG–body mass index (TyG–BMI), TyG–waist circumference (TyG–WC), and TyG–waist-to-height ratio (TyG–WHtR), were assessed. Cox proportional hazards models were employed to determine the association between these parameters and the incidence of diabetes mellitus, with adjustments made for demographic, lifestyle, and health-related characteristics.
Results:
Higher levels of all TyG–related parameters were significantly associated with an increased risk of developing diabetes mellitus. Specifically, participants in the highest quartile of the TyG index, TyG–BMI, TyG–WC, and TyG–WHtR exhibited significantly higher hazard ratios for diabetes mellitus incidence compared with those in the lowest quartile (p<.001 for all). Notably, the TyG index demonstrated a stronger predictive value for diabetes mellitus than traditional measures such as the homeostatic model assessment of insulin resistance.
Conclusion
TyG–related parameters are robust predictors of diabetes mellitus incidence in Korean adults. These findings support the incorporation of TyG–related measures into clinical settings for the early identification and intervention of high-risk populations. Utilizing these parameters for early diagnosis and preventive strategies may significantly enhance diabetes mellitus management.
7.Triglyceride-glucose parameters as predictors of diabetes mellitus incidence in Korean adults: a secondary analysis of a Prospective Cohort Study
Yu Jin PARK ; Miseon SHIN ; Hyun Seon JEON ; Eun Hee YANG
Journal of Korean Academy of Nursing 2025;55(2):205-221
Purpose:
This study aimed to evaluate the association between triglyceride-glucose (TyG)–related parameters and the incidence of diabetes mellitus in Korean adults. Data were obtained from the Korean Genome and Epidemiology Study (KoGES).
Methods:
This secondary analysis examined data from 6,816 adults aged 40–69 years who participated in the KoGES from 2001 to 2020. TyG–related parameters, including the TyG index, TyG–body mass index (TyG–BMI), TyG–waist circumference (TyG–WC), and TyG–waist-to-height ratio (TyG–WHtR), were assessed. Cox proportional hazards models were employed to determine the association between these parameters and the incidence of diabetes mellitus, with adjustments made for demographic, lifestyle, and health-related characteristics.
Results:
Higher levels of all TyG–related parameters were significantly associated with an increased risk of developing diabetes mellitus. Specifically, participants in the highest quartile of the TyG index, TyG–BMI, TyG–WC, and TyG–WHtR exhibited significantly higher hazard ratios for diabetes mellitus incidence compared with those in the lowest quartile (p<.001 for all). Notably, the TyG index demonstrated a stronger predictive value for diabetes mellitus than traditional measures such as the homeostatic model assessment of insulin resistance.
Conclusion
TyG–related parameters are robust predictors of diabetes mellitus incidence in Korean adults. These findings support the incorporation of TyG–related measures into clinical settings for the early identification and intervention of high-risk populations. Utilizing these parameters for early diagnosis and preventive strategies may significantly enhance diabetes mellitus management.
8.Triglyceride-glucose parameters as predictors of diabetes mellitus incidence in Korean adults: a secondary analysis of a Prospective Cohort Study
Yu Jin PARK ; Miseon SHIN ; Hyun Seon JEON ; Eun Hee YANG
Journal of Korean Academy of Nursing 2025;55(2):205-221
Purpose:
This study aimed to evaluate the association between triglyceride-glucose (TyG)–related parameters and the incidence of diabetes mellitus in Korean adults. Data were obtained from the Korean Genome and Epidemiology Study (KoGES).
Methods:
This secondary analysis examined data from 6,816 adults aged 40–69 years who participated in the KoGES from 2001 to 2020. TyG–related parameters, including the TyG index, TyG–body mass index (TyG–BMI), TyG–waist circumference (TyG–WC), and TyG–waist-to-height ratio (TyG–WHtR), were assessed. Cox proportional hazards models were employed to determine the association between these parameters and the incidence of diabetes mellitus, with adjustments made for demographic, lifestyle, and health-related characteristics.
Results:
Higher levels of all TyG–related parameters were significantly associated with an increased risk of developing diabetes mellitus. Specifically, participants in the highest quartile of the TyG index, TyG–BMI, TyG–WC, and TyG–WHtR exhibited significantly higher hazard ratios for diabetes mellitus incidence compared with those in the lowest quartile (p<.001 for all). Notably, the TyG index demonstrated a stronger predictive value for diabetes mellitus than traditional measures such as the homeostatic model assessment of insulin resistance.
Conclusion
TyG–related parameters are robust predictors of diabetes mellitus incidence in Korean adults. These findings support the incorporation of TyG–related measures into clinical settings for the early identification and intervention of high-risk populations. Utilizing these parameters for early diagnosis and preventive strategies may significantly enhance diabetes mellitus management.
9.Effect of remimazolam on intraoperative hemodynamic stability in patients undergoing cerebrovascular bypass surgery: a prospective randomized controlled trial
Chang-Hoon KOO ; Si Un LEE ; Hyeong-Geun KIM ; Soowon LEE ; Yu Kyung BAE ; Ah-Young OH ; Young-Tae JEON ; Jung-Hee RYU
Korean Journal of Anesthesiology 2025;78(2):148-158
Background:
Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery.
Methods:
Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil.
Results:
Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group.
Conclusions
Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.
10.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.

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