1.Licochalcone D Exerts Antitumor Activity in Human Colorectal Cancer Cells by Inducing ROS Generation and Phosphorylating JNK and p38 MAPK
Seung-On LEE ; Sang Hoon JOO ; Seung-Sik CHO ; Goo YOON ; Yung Hyun CHOI ; Jin Woo PARK ; Kwon-Yeon WEON ; Jung-Hyun SHIM
Biomolecules & Therapeutics 2025;33(2):344-354
Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.
2.Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data
Kyu Yean KIM ; Ho Cheol KIM ; Tae Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang Gun SUH ; Chang Hoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jae Hyun JEON ; Chi Young JUNG ; Jeong Su CHO ; Yoo Duk CHOI ; Seung Sik HWANG ; Chang Min CHOI ; Seung Hun JANG ; Jeong Uk LIM ;
Cancer Research and Treatment 2025;57(1):83-94
Purpose:
Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.
Materials and Methods:
Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.
Results:
A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.
Conclusion
Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.
3.Analysis of Changes in Relative Value Scale and Frequency of Surgery and Procedures in Surgery Departments Over the Past 18 Years: Secondary Publication
Jae Hoon CHO ; Sei Young LEE ; Seung Hoon LEE ; Seog-Kyun MUN ; Jung Hyun CHANG ; Chan-Soon PARK
Korean Journal of Otolaryngology - Head and Neck Surgery 2025;68(2):67-73
Background and Objectives:
The purpose of this study was to compare and analyze the 18- year change in the relative value scale (RVS) in otolaryngology in relation to other surgical departments so as to help make future policy decisions.Subjects and Method Data on RVSs and addition rates, the deparments of main managed care, frequency of practice, and number of specialists were collected for all surgeries and procedures conducted in 2004, 2008, 2013, 2018, and 2022. Among these, an analysis was conducted for nine surgical departments. The number of surgeries and procedure items, the median value of the RVS, and the usage amount (i.e., RVS of all items multiplied by the frequency of surgeries and procedures) were calculated.
Results:
Over the past 18 years, the increase in the number of surgeries, procedure items and RVS in otolaryngology has grown smaller than that in other surgical departments, and the usage has decreased very sharply; in essence, the usage per specialist has actually decreased compared to 18 years ago.
Conclusion
Compared to other departments, RVS in otorhinolaryngology has shown very little change over the past period of 18 years. It is necessary to reasonably increase the currently undervalued RVS in otorhinolaryngology, particularly focusing on surgeries and procedures.
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.Association of Nutritional Intake with Physical Activity and Handgrip Strength in Individuals with Airflow Limitation
I Re HEO ; Tae Hoon KIM ; Jong Hwan JEONG ; Manbong HEO ; Sun Mi JU ; Jung-Wan YOO ; Seung Jun LEE ; Yu Ji CHO ; Yi Yeong JEONG ; Jong Deog LEE ; Ho Cheol KIM
Tuberculosis and Respiratory Diseases 2025;88(1):120-129
Background:
We investigated whether nutritional intake is associated with physical activity (PA) and handgrip strength (HGS) in individuals with airflow limitation.
Methods:
This study analyzed data from the 2014 and 2016 Korean National Health and Nutrition Examination Survey. We assessed total protein intake (g/day), caloric intake (kcal/day), and other nutritional intakes, using a 24-hour dietary recall questionnaire. HGS was measured three times for each hand using a digital grip strength dynamometer, and PA was assessed as health-enhancing PA. Airflow limitation was defined as a forced expiratory volume/forced vital capacity ratio of 0.7 in individuals over 40 years of age. Participants were categorized into groups based on their PA levels and HGS measurements: active aerobic PA vs. non-active aerobic PA, and normal HGS vs. low HGS.
Results:
Among the 622 individuals with airflow limitation, those involved in active aerobic PA and those with higher HGS had notably higher total food, calorie, water, protein, and lipid intake. The correlations between protein and caloric intake with HGS were strong (correlation coefficients=0.344 and 0.346, respectively). The forest plots show that higher intakes of food, water, calories, protein, and lipids are positively associated with active aerobic PA, while higher intakes of these nutrients are inversely associated with low HGS. However, in the multivariate logistic regression analysis, no significant associations were observed between nutritional intake and active aerobic PA or HGS.
Conclusion
Nutritional intake was found to not be an independent factor associated with PA and HGS. However, the observed correlations suggest potential indirect effects that warrant further investigation.
6.Analysis of Changes in Relative Value Scale and Frequency of Surgery and Procedures in Surgery Departments Over the Past 18 Years: Secondary Publication
Jae Hoon CHO ; Sei Young LEE ; Seung Hoon LEE ; Seog-Kyun MUN ; Jung Hyun CHANG ; Chan-Soon PARK
Korean Journal of Otolaryngology - Head and Neck Surgery 2025;68(2):67-73
Background and Objectives:
The purpose of this study was to compare and analyze the 18- year change in the relative value scale (RVS) in otolaryngology in relation to other surgical departments so as to help make future policy decisions.Subjects and Method Data on RVSs and addition rates, the deparments of main managed care, frequency of practice, and number of specialists were collected for all surgeries and procedures conducted in 2004, 2008, 2013, 2018, and 2022. Among these, an analysis was conducted for nine surgical departments. The number of surgeries and procedure items, the median value of the RVS, and the usage amount (i.e., RVS of all items multiplied by the frequency of surgeries and procedures) were calculated.
Results:
Over the past 18 years, the increase in the number of surgeries, procedure items and RVS in otolaryngology has grown smaller than that in other surgical departments, and the usage has decreased very sharply; in essence, the usage per specialist has actually decreased compared to 18 years ago.
Conclusion
Compared to other departments, RVS in otorhinolaryngology has shown very little change over the past period of 18 years. It is necessary to reasonably increase the currently undervalued RVS in otorhinolaryngology, particularly focusing on surgeries and procedures.
7.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.
8.Association of Nutritional Intake with Physical Activity and Handgrip Strength in Individuals with Airflow Limitation
I Re HEO ; Tae Hoon KIM ; Jong Hwan JEONG ; Manbong HEO ; Sun Mi JU ; Jung-Wan YOO ; Seung Jun LEE ; Yu Ji CHO ; Yi Yeong JEONG ; Jong Deog LEE ; Ho Cheol KIM
Tuberculosis and Respiratory Diseases 2025;88(1):120-129
Background:
We investigated whether nutritional intake is associated with physical activity (PA) and handgrip strength (HGS) in individuals with airflow limitation.
Methods:
This study analyzed data from the 2014 and 2016 Korean National Health and Nutrition Examination Survey. We assessed total protein intake (g/day), caloric intake (kcal/day), and other nutritional intakes, using a 24-hour dietary recall questionnaire. HGS was measured three times for each hand using a digital grip strength dynamometer, and PA was assessed as health-enhancing PA. Airflow limitation was defined as a forced expiratory volume/forced vital capacity ratio of 0.7 in individuals over 40 years of age. Participants were categorized into groups based on their PA levels and HGS measurements: active aerobic PA vs. non-active aerobic PA, and normal HGS vs. low HGS.
Results:
Among the 622 individuals with airflow limitation, those involved in active aerobic PA and those with higher HGS had notably higher total food, calorie, water, protein, and lipid intake. The correlations between protein and caloric intake with HGS were strong (correlation coefficients=0.344 and 0.346, respectively). The forest plots show that higher intakes of food, water, calories, protein, and lipids are positively associated with active aerobic PA, while higher intakes of these nutrients are inversely associated with low HGS. However, in the multivariate logistic regression analysis, no significant associations were observed between nutritional intake and active aerobic PA or HGS.
Conclusion
Nutritional intake was found to not be an independent factor associated with PA and HGS. However, the observed correlations suggest potential indirect effects that warrant further investigation.
9.Outcomes of Deferring Percutaneous Coronary Intervention Without Physiologic Assessment for Intermediate Coronary Lesions
Jihoon KIM ; Seong-Hoon LIM ; Joo-Yong HAHN ; Jin-Ok JEONG ; Yong Hwan PARK ; Woo Jung CHUN ; Ju Hyeon OH ; Dae Kyoung CHO ; Yu Jeong CHOI ; Eul-Soon IM ; Kyung-Heon WON ; Sung Yun LEE ; Sang-Wook KIM ; Ki Hong CHOI ; Joo Myung LEE ; Taek Kyu PARK ; Jeong Hoon YANG ; Young Bin SONG ; Seung-Hyuk CHOI ; Hyeon-Cheol GWON
Korean Circulation Journal 2025;55(3):185-195
Background and Objectives:
Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment.
Methods:
A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years.
Results:
The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization.
Conclusions
For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.
10.YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12
Hongyan ZHOU ; Hae Jin KEE ; Le WAN ; Yodita ASFAHA ; Fabian FISCHER ; Matthias U KASSACK ; Thomas KURZ ; Seong Hoon KIM ; Seung-Jung KEE ; Young Joon HONG ; Myung Ho JEONG
Korean Circulation Journal 2025;55(3):231-247
Background and Objectives:
Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism.
Methods:
New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12).
Results:
YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes.
Conclusions
YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

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