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.Long-Term Incidence of Gastrointestinal Bleeding Following Ischemic Stroke
Jun Yup KIM ; Beom Joon KIM ; Jihoon KANG ; Do Yeon KIM ; Moon-Ku HAN ; Seong-Eun KIM ; Heeyoung LEE ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Tai Hwan PARK ; Kyungbok LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Keun-Sik HONG ; Kang-Ho CHOI ; Joon-Tae KIM ; Dong-Eog KIM ; Jay Chol CHOI ; Mi-Sun OH ; Kyung-Ho YU ; Byung-Chul LEE ; Kwang-Yeol PARK ; Ji Sung LEE ; Sujung JANG ; Jae Eun CHAE ; Juneyoung LEE ; Min-Surk KYE ; Philip B. GORELICK ; Hee-Joon BAE ;
Journal of Stroke 2025;27(1):102-112
Background:
and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes.
Methods:
We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data.
Results:
Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4.
Conclusion
Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.
3.Prevalence of asymptomatic malaria in high- and low-transmission areas of Tanzania: The role of asymptomatic carriers in malaria persistence and the need for targeted surveillance and control efforts
Ernest MAZIGO ; Hojong JUN ; Wang-Jong LEE ; Johnsy Mary LOUIS ; Fadhila FITRIANA ; Jadidan Hada SYAHADA ; Fauzi MUH ; Feng LU ; Md Atique AHMED ; Seok Ho CHA ; Wanjoo CHUN ; Won Sun PARK ; Se Jin LEE ; Sunghun NA ; Joon-Hee HAN ; Nyalali KIJA ; Smart GEODFREY ; Eun-Teak HAN ; Jim TODD ; Alphaxard MANJURANO ; Winifrida KIDIMA ; Jin-Hee HAN
Parasites, Hosts and Diseases 2025;63(1):57-65
As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.
4.Characteristics and outcomes of portal vein thrombosis in patients with inflammatory bowel disease in Korea
Ki Jin KIM ; Su-Bin SONG ; Jung-Bin PARK ; June Hwa BAE ; Ji Eun BAEK ; Ga Hee KIM ; Min-Jun KIM ; Seung Wook HONG ; Sung Wook HWANG ; Dong-Hoon YANG ; Byong Duk YE ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Chang Sik YU ; Yong-Sik YOON ; Jong-Lyul LEE ; Min Hyun KIM ; Ho-Su LEE ; Sang Hyoung PARK
The Korean Journal of Internal Medicine 2025;40(2):243-250
Background/Aims:
Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea.
Methods:
This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans.
Results:
A total of 78 patients met the study’s criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR.
Conclusions
Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.
5.Patient-specific predictors of successful frozen embryo transfer using the freeze-all protocol: a retrospective observational study
Hyun Joo LEE ; Eun Hee YU ; Jong Kil JOO
Journal of Yeungnam Medical Science 2025;42(1):28-
Background:
The aim of this study was to examine various patient factors affecting first programmed embryo transfer (ET) outcomes under the freeze-all policy at a single tertiary university infertility center.
Methods:
This retrospective observational study reviewed the medical records of 243 couples who underwent their first ET using blastocysts collected under the freeze-all antagonist-controlled ovarian stimulation (COS) protocol from 2015 to 2023. Patients were grouped into pregnant and nonpregnant groups, and their data, including demographics, COS and ET outcomes, and embryo storage duration, were analyzed.
Results:
Patient body mass index, cause of infertility, follicle-to-oocyte index, distribution of blastocyst grades, number of transferred embryos, and embryo storage duration were not significantly different between the groups. In a simple comparative analysis, patients with successful clinical pregnancy tended to have significantly lower female and male age (33.83±3.67 and 35.32±4.54 years vs. 37.07±4.15 and 39.33±5.60 years, respectively), higher anti-Müllerian hormone levels (6.27±5.32 ng/mL vs. 4.14±3.82 ng/mL) and antral follicle counts (14.20±8.26 vs. 10.04±5.75), and higher numbers of retrieved oocytes and metaphase II oocytes (13.74±6.92 and 9.64±6.19 vs. 11.21±6.04 and 7.53±5.56, respectively). Multivariate logistic regression analysis of these variables revealed that only male age was a significant factor for successful clinical pregnancy (odds ratio, 4.768; 95% confidence interval, 1.252–18.162; p=0.022).
Conclusion
During the first programmed ET using blastocysts collected under the freeze-all antagonist COS protocol, male age and correspondingly the quality of gametes for fertilization were crucial for successful pregnancy, having more importance than calculated female ovarian reserve and embryo storage duration.
6.Impact of Meal Frequency on Insulin Resistance in Middle-Aged and Older Adults: A Prospective Cohort Study
Ha-Eun RYU ; Jong Hee LEE ; Byoungjin PARK ; Seok-Jae HEO ; Yu-Jin KWON
Diabetes & Metabolism Journal 2025;49(2):311-320
Background:
Insulin resistance (IR) is central to metabolic disorders and significantly influenced by diet. Studies on meal frequency (MF) and metabolic indicators have shown mixed results. This study explores the link between MF and IR in middle-aged and older adults.
Methods:
This prospective cohort study included 4,570 adults aged 40 to 69 years from the Korean Genome and Epidemiologic Study. MF were divided into two groups based on whether they consumed three or more, or fewer than three, meals daily. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR); participants were classified as IR if their HOMA-IR value was ≥2.5. Multiple Cox proportional hazard regression analyses were conducted to examine the association between MF and the incidence of IR.
Results:
After adjusting for all variables, individuals in the MF ≥3 group showed a reduced incidence of IR compared to those in the MF <3 group (hazard ratio, 0.880; 95% confidence interval, 0.782 to 0.990). Additionally, subgroup analyses by sex, diabetes mellitus (DM), and body mass index (BMI) showed that this association persisted only in men, individuals without DM, and those with a BMI <25.
Conclusion
Our findings indicate that a higher MF among middle-aged and older adults is associated with a reduced incidence of IR. However, this association was maintained only in men, individuals without DM, and those without obesity.
7.Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study
Songji CHOI ; Se Hyun KIM ; Sejoon LEE ; Jeongmin SEO ; Minsu KANG ; Eun Hee JUNG ; Sang-A KIM ; Koung Jin SUH ; Ji Yun LEE ; Ji-Won KIM ; Jin Won KIM ; Jeong-Ok LEE ; Yu Jung KIM ; Keun-Wook LEE ; Jee Hyun KIM ; Soo-Mee BANG ; Jong Seok LEE
Cancer Research and Treatment 2025;57(1):70-82
Purpose:
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods:
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results:
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.
8.KASL clinical practice guidelines for the management of metabolic dysfunction-associated steatotic liver disease 2025
Won SOHN ; Young-Sun LEE ; Soon Sun KIM ; Jung Hee KIM ; Young-Joo JIN ; Gi-Ae KIM ; Pil Soo SUNG ; Jeong-Ju YOO ; Young CHANG ; Eun Joo LEE ; Hye Won LEE ; Miyoung CHOI ; Su Jong YU ; Young Kul JUNG ; Byoung Kuk JANG ;
Clinical and Molecular Hepatology 2025;31(Suppl):S1-S31
9.Effects of Pressure Hemostasis Band Application on Bleeding, Pain, and Discomfort after Bone Marrow Examination
Jin Hee JUNG ; Bo-Eun KIM ; Ji Sook JU ; Mi RYU ; So Young CHOE ; Jong Hee CHOI ; Soo-Mee BANG ; Jeong-Ok LEE ; Ji Yun LEE ; Sang-A KIM
Asian Oncology Nursing 2025;25(1):17-27
Purpose:
The purpose of this study was to develop an approach to alleviate the discomfort caused by sandbag compression after a bone marrow examination. This research examined the effects of applying a pressure hemostasis band on bleeding, pain, and discomfort at the bone marrow examination site.
Methods:
This study was conducted with a nonequivalent control group non-synchronized design. For 74 patients under evaluation who underwent bone marrow examination, sandbag compression was applied to the examination site in the control group (n=37), and a pressure hemostasis band was applied to the intervention group (n=37). In both groups, absolute bed rest was performed for two hours, and bleeding, pain, and discomfort at the examination site were measured.
Results:
After two hours of the bone marrow examination, there was no difference in bleeding on the gauze between the two groups (F=0.59, p=.444). Bleeding occurred in three patients in the intervention group and six in the control group (χ 2 =1.14, p=.479), with no cases of hematoma detected in either group. One hour post-examination, the control group experienced significantly higher pain (F=5.45, p=.022) and discomfort (F=5.68, p=.020) than the intervention group. However, pain and discomfort levels were similar between groups after two hours.
Conclusion
Compared to the sandbag compression group, the band application group showed no difference in bleeding and experienced less pain and discomfort at the examination site. This confirms that the pressure hemostasis band is a suitable alternative to sandbag compression in post-examination care.
10.Prevalence of asymptomatic malaria in high- and low-transmission areas of Tanzania: The role of asymptomatic carriers in malaria persistence and the need for targeted surveillance and control efforts
Ernest MAZIGO ; Hojong JUN ; Wang-Jong LEE ; Johnsy Mary LOUIS ; Fadhila FITRIANA ; Jadidan Hada SYAHADA ; Fauzi MUH ; Feng LU ; Md Atique AHMED ; Seok Ho CHA ; Wanjoo CHUN ; Won Sun PARK ; Se Jin LEE ; Sunghun NA ; Joon-Hee HAN ; Nyalali KIJA ; Smart GEODFREY ; Eun-Teak HAN ; Jim TODD ; Alphaxard MANJURANO ; Winifrida KIDIMA ; Jin-Hee HAN
Parasites, Hosts and Diseases 2025;63(1):57-65
As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.

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