1.Stress Accelerates Depressive-Like Behaviors through Increase of Notch2 Expression in N141I Mutation Presenilin-2 Transgenic Mice
Seung Sik YOO ; Sun Mi GU ; Kyung Tak NAM ; Jeong Soon CHOI ; Yong Sun LEE ; In Jun YEO ; Ji Eun YU ; Sanghyeon KIM ; Dong Won LEE ; Hyeon Joo HAM ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2026;34(3):544-555
Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.
2.Diagnostic and prognostic performance of PAK1 methylation in patients with hepatocellular carcinoma undergoing liver transplantation
Shin HWANG ; Hyo Jung KO ; Eunyoung TAK ; Kyoung-Jin LEE ; Yun-Kyu LEE
Clinical Transplantation and Research 2026;40(1):104-115
Background:
DNA methylation is under investigation as an early diagnostic biomarker for cancers such as hepatocellular carcinoma (HCC). p21-activated protein kinase 1 (PAK1) demonstrates a high methylation tendency in HCC. We assessed the diagnostic and prognostic performance of PAK1 methylation in liver transplantation (LT) recipients with and without HCC.
Methods:
To assess PAK1 methylation, stored pretransplant blood samples from LT recipients were analyzed by droplet digital polymerase chain reaction.
Results:
This study included 274 patients with HCC and 100 control patients without the disease. Ten-year survival rates in the HCC and control groups were 60.5% and 80.6%, respectively (P=0.001). The 10-year HCC recurrence rate was 39.0%. Ten-year survival rates in the HCC recurrence and nonrecurrence groups were 13.3% and 91.2%, respectively (P<0.001); median PAK1 methylation levels in the control and HCC groups were 50.0 and 108.0 copies (P=0.102). The area under the receiver operating characteristic curve was 0.599, and the Youden J index was 0.199, indicating 57.9% sensitivity and 62.0% specificity at a cutoff of 78 copies. With a cutoff of 5 copies, sensitivity was 94.1% and specificity was 14.0%. The positive likelihood ratio was 1.09 and the negative likelihood ratio was 0.42, indicating diagnostic accuracy below α-fetoprotein and protein induced by vitamin K absence or antagonist-II. PAK1 cutoffs of 5 and 10 copies did not affect HCC recurrence, but a cutoff of 2 copies appeared associated with lower recurrence.
Conclusions
These data suggest that PAK1 methylation is not a clinically useful biomarker for HCC in LT recipients. New DNA methylation biomarkers are required for early diagnosis.
3.Association between Breakfast Consumption Frequency and Chronic Inflammation in Korean Adult Males: Korea National Health and Nutrition Examination Survey 2016–2018
Eun Ji HAN ; Eun Ju PARK ; Sae Rom LEE ; Sang Yeoup LEE ; Young Hye CHO ; Young In LEE ; Jung In CHOI ; Ryuk Jun KWON ; Soo Min SON ; Yun Jin KIM ; Jeong Gyu LEE ; Yu Hyeon YI ; Young Jin TAK ; Seung Hun LEE ; Gyu Lee KIM ; Young Jin RA
Korean Journal of Family Medicine 2025;46(2):92-97
Background:
Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker.
Methods:
A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests.
Results:
Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036).
Conclusion
Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.
4.Association between Breakfast Consumption Frequency and Chronic Inflammation in Korean Adult Males: Korea National Health and Nutrition Examination Survey 2016–2018
Eun Ji HAN ; Eun Ju PARK ; Sae Rom LEE ; Sang Yeoup LEE ; Young Hye CHO ; Young In LEE ; Jung In CHOI ; Ryuk Jun KWON ; Soo Min SON ; Yun Jin KIM ; Jeong Gyu LEE ; Yu Hyeon YI ; Young Jin TAK ; Seung Hun LEE ; Gyu Lee KIM ; Young Jin RA
Korean Journal of Family Medicine 2025;46(2):92-97
Background:
Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker.
Methods:
A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests.
Results:
Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036).
Conclusion
Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.
5.Association between Breakfast Consumption Frequency and Chronic Inflammation in Korean Adult Males: Korea National Health and Nutrition Examination Survey 2016–2018
Eun Ji HAN ; Eun Ju PARK ; Sae Rom LEE ; Sang Yeoup LEE ; Young Hye CHO ; Young In LEE ; Jung In CHOI ; Ryuk Jun KWON ; Soo Min SON ; Yun Jin KIM ; Jeong Gyu LEE ; Yu Hyeon YI ; Young Jin TAK ; Seung Hun LEE ; Gyu Lee KIM ; Young Jin RA
Korean Journal of Family Medicine 2025;46(2):92-97
Background:
Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker.
Methods:
A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests.
Results:
Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036).
Conclusion
Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.
6.Association between Breakfast Consumption Frequency and Chronic Inflammation in Korean Adult Males: Korea National Health and Nutrition Examination Survey 2016–2018
Eun Ji HAN ; Eun Ju PARK ; Sae Rom LEE ; Sang Yeoup LEE ; Young Hye CHO ; Young In LEE ; Jung In CHOI ; Ryuk Jun KWON ; Soo Min SON ; Yun Jin KIM ; Jeong Gyu LEE ; Yu Hyeon YI ; Young Jin TAK ; Seung Hun LEE ; Gyu Lee KIM ; Young Jin RA
Korean Journal of Family Medicine 2025;46(2):92-97
Background:
Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker.
Methods:
A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests.
Results:
Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036).
Conclusion
Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.
7.A Comparative Study of Three National Surveys on Biliary Atresia by the Korean Association of Pediatric Surgeons
Yeon Jun JEONG ; Dayoung KO ; Hyunhee KWON ; Ki Hoon KIM ; Dae Yeon KIM ; Soo-Hong KIM ; Wontae KIM ; Hae-Young KIM ; Hyun Young KIM ; Seong Chul KIM ; Younghyun NA ; Jung-Man NAMGOONG ; So Hyun NAM ; Junbeom PARK ; Jinyoung PARK ; Tae-Jun PARK ; Jeong-Meen SEO ; Ji-Young SUL ; Joonhyuk SON ; Hyun Beak SHIN ; Joohyun SIM ; Soo Min AHN ; Hee Beom YANG ; Jung-Tak OH ; Chaeyoun OH ; Joong Kee YOUN ; Sanghoon LEE ; Ju Yeon LEE ; Kyong IHN ; Hye Kyung CHANG ; Eunyoung JUNG ; Jae Hee CHUNG ; Yu Jeong CHO ; Yun Mee CHOE ; Soo Jin Na CHOI ; Seok Joo HAN ; In Geol HO ; Ji-Won HAN
Advances in Pediatric Surgery 2025;31(2):47-58
Purpose:
Biliary atresia (BA) is a rare but progressive cholangiopathy and the leading cause of pediatric liver transplantation worldwide. The Korean Association of Pediatric Surgeons (KAPS) has conducted three national surveys (2001, 2011, and 2023) to assess long-term trends in the diagnosis, treatment, and outcomes of BA. This study provides a comparative analysis of the 2nd and 3rd national surveys, with reference to selected findings from the 1st survey.
Methods:
This study included 453 patients from the 3rd national survey (2011–2021) and 435 patients from the 2nd survey (2001–2010), all of whom underwent Kasai portoenterostomy. Data were collected via electronic case report forms from pediatric surgical centers nationwide. Comparisons were made regarding demographics, clinical features, diagnostic patterns, operative details, follow-up outcomes, and survival. Kaplan–Meier analysis was used to evaluate long-term survival.
Results:
The mean number of BA patients per year remained stable between surveys (43.5 in the 2nd, 41.18 in the 3rd), though centralization of care increased, with 61.5% of cases managed by two major institutions in the 3rd survey. The median age at surgery decreased, and the use of preoperative imaging (especially magnetic resonance cholangiopancreatography) increased. The 10-year native liver survival rate declined from 59.8% to 53.7%, while overall 10-year survival improved slightly (92.9% to 93.2%). Postoperative complications, such as cholangitis and liver failure, persisted but were better categorized. The 3rd survey also reported improved mortality (4.9%) and reduced follow-up loss (11.5%) compared to the 2nd survey.
Conclusion
While overall survival after Kasai operation has remained high and even improved, native liver survival has slightly declined. The findings reflect earlier diagnosis, more consistent diagnostic imaging, and increasing centralization of care. These trends underscore the importance of long-term nationwide data collection in guiding future strategies for BA management in Korea.
8.Usefulness and Safety of 0.4% Sodium Hyaluronate as a Submucosal Injection Solution in Rabbits
Deok-Jin TAK ; Eun-Hee YUN ; Seong-Won AN ; Eun-Jik KIM ; Jinsu KANG ; Young-Sam KWON
Journal of Veterinary Clinics 2025;42(2):71-78
Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) with submucosal saline injection are well-established methods for excising nonpolypoid early neoplastic lesions of the gastrointestinal tract in humans. In EMR and ESD, this submucosal injection forms a bulla that lifts the lesion, provides a safety cushion during resection, and reduces the risk of perforation. Commonly used solutions include normal saline (NS), 10% glycerol, and 0.4% sodium hyaluronate (SH). Among these, 0.4% SH is the most preferred solution in humans due to its slow absorption. While the usefulness of EMR and ESD in humans has been well-documented, information on its application in veterinary medicine remains limited. This study aimed to compare the usefulness and safety of 0.4% SH with 10% glycerol and NS as a gastric submucosal injection solution in rabbits with goals of providing a veterinary perspective on the application of submucosal injection solutions and highlighting the clinical relevance for endoscopic procedures in animals. A conventional gastrotomy was performed to expose the gastric lumen, followed by a submucosal injection. In macroscopic evaluations of mucosal elevation using a digital caliper, 0.4% SH showed a statistically significant elevation effect compared with NS, unlike 10% glycerol. Histomorphometric analysis further revealed that 0.4% SH maintained submucosal space expansion for the longest duration. In addition, histopathological analysis showed no tissue damage except for hemorrhage across all of the submucosal injection groups. In conclusion, 0.4% SH is considered the most preferable submucosal injection material in veterinary medicine, particularly for its usefulness and safety. Based on the results of this study, minimally invasive techniques such as EMR and ESD are expected to be applicable in animals. This study provides the first veterinary-specific evaluation of 0.4% SH as a submucosal injection solution in endoscopic resection (ER), demonstrating its potential benefits in minimally invasive endoscopic procedures. The findings suggest that 0.4% SH may enhance the safety and efficacy of ER, making it a preferable choice for submucosal injection in this context in veterinary medicine.
9.Cellular expansion of hepatocellular carcinoma organoids using decellularized liver scaffolds
Shin HWANG ; I-Ji JUNG ; Kyoung-Jin LEE ; Yun-Kyu KIM ; Eunyoung TAK
Clinical Transplantation and Research 2025;39(4):366-377
Background:
A decellularized liver scaffold (DLS) is a three-dimensional acellular extracellular matrix created by removing cellular components from liver tissue. Hepatocellular carcinoma (HCC) organoids represent a useful experimental model.
Methods:
HCC organoids from patient-derived xenografts (PDX), liver organoids, and HepG2 cells were expanded by cultivation within a murine DLS.
Results:
HCC and liver organoids were generated from HCC PDX and human liver tissues, respectively. Expression levels of hepatocyte paraffin 1 (HepPar1), epithelial cell adhesion molecule (EpCAM), alpha-fetoprotein, keratin-7, and keratin-19 were detected in normal liver tissue, HCC tissue, HCC PDX, and HCC organoids. Fifteen murine DLSs were created, and the complete absence of liver cells was confirmed histologically by Masson trichrome and periodic acid–Schiff staining. Culture of HCC organoids in the DLS resulted in the expansion of numerous HCC cells scattered throughout the DLS framework. Keratin-7 expression was abundant, indicating widely dispersed progenitor cells. In contrast, cultivation of HepG2 cells within the DLS resulted in sparse cell distribution throughout the scaffold. Human hepatocyte organoids could not be cultivated successfully within the murine DLS framework.
Conclusions
The DLS collagen framework facilitates the proliferation of HCC organoids. Thus, cultivating HCC organoids within a DLS appears to represent an effective method for rapid cell expansion, although it was ineffective for HepG2 cells and liver organoids. Further studies are required to validate the biological and oncological equivalence between seeded HCC organoids and those rapidly expanded within a DLS.
10.An explanatory study on periodontal disease programs by public health centers in Korea
Na-Yeon TAK ; Su-Jin KIM ; Jae-In RYU ; Belong CHO ; Nam-Yoon KIM ; Seung-Min YANG ; Kyoung-Man MIN ; In-Woo CHO ; Ji-Young HAN ; Seung-Yun SHIN
Journal of Korean Academy of Oral Health 2024;48(4):186-191
Objectives:
This study aimed to investigate the current status of periodontal disease programs implemented by public health centers in the Republic of Korea.
Methods:
An explanatory survey was conducted by the Ministry of Health and Welfare from October to November 2023. The survey focused on the periodontal programs and the implementation status across different stages. Distributed and collected via Google Forms, the survey targeted 196 oral health teams within public health centers in Korea. A total of 109 public health centers responded to the study questionnaire, yielding a participation rate of 55.6%. Data were analyzed using IBM SPSS Statistics for Windows, version 26.
Results:
A majority of periodontal disease programs were implemented exclusively by oral health teams, with a rate of 33.0%. The implementation rate of collaboration with home-visiting health teams was 17.4% and with other teams was 10.1%. The implementation rates of periodontal management across stages were as follows: 11.9% for periodontal examination, 18.3% for periodontal treatment, and 11.9% for sustainable periodontal care.
Conclusions
Periodontal disease programs are predominantly conducted by oral health teams with limited collaboration across other health teams. Additionally, periodontal management activities, such as examinations and treatments, remain insufficient. Integration between oral health teams and other health teams within public health centers or private dental clinics should be improved.

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