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.

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.

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.

The prevalence of drug-induced liver injury (DILI) and viral liver infections presents significant challenges in modern healthcare and contributes to considerable morbidity and mortality worldwide. Concurrently, metabolic dysfunctionassociated steatotic liver disease (MASLD) has emerged as a major public health concern, reflecting the increasing rates of obesity and leading to more severe complications such as fibrosis and hepatocellular carcinoma. X-box binding protein 1 (XBP1) is a distinct transcription factor with a basic-region leucine zipper structure, whose activity is regulated by alternative splicing in response to disruptions in endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR) activation. XBP1 interacts with a key signaling component of the highly conserved UPR and is critical in determining cell fate when responding to ER stress in liver diseases. This review aims to elucidate the emerging roles and molecular mechanisms of XBP1 in liver pathogenesis, focusing on its involvement in DILI, viral liver infections, MASLD, fibrosis/cirrhosis, and liver cancer. Understanding the multifaceted functions of XBP1 in these liver diseases offers insights into potential therapeutic strategies to restore ER homeostasis and mitigate liver damage.

The prevalence of drug-induced liver injury (DILI) and viral liver infections presents significant challenges in modern healthcare and contributes to considerable morbidity and mortality worldwide. Concurrently, metabolic dysfunctionassociated steatotic liver disease (MASLD) has emerged as a major public health concern, reflecting the increasing rates of obesity and leading to more severe complications such as fibrosis and hepatocellular carcinoma. X-box binding protein 1 (XBP1) is a distinct transcription factor with a basic-region leucine zipper structure, whose activity is regulated by alternative splicing in response to disruptions in endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR) activation. XBP1 interacts with a key signaling component of the highly conserved UPR and is critical in determining cell fate when responding to ER stress in liver diseases. This review aims to elucidate the emerging roles and molecular mechanisms of XBP1 in liver pathogenesis, focusing on its involvement in DILI, viral liver infections, MASLD, fibrosis/cirrhosis, and liver cancer. Understanding the multifaceted functions of XBP1 in these liver diseases offers insights into potential therapeutic strategies to restore ER homeostasis and mitigate liver damage.

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.

The prevalence of drug-induced liver injury (DILI) and viral liver infections presents significant challenges in modern healthcare and contributes to considerable morbidity and mortality worldwide. Concurrently, metabolic dysfunctionassociated steatotic liver disease (MASLD) has emerged as a major public health concern, reflecting the increasing rates of obesity and leading to more severe complications such as fibrosis and hepatocellular carcinoma. X-box binding protein 1 (XBP1) is a distinct transcription factor with a basic-region leucine zipper structure, whose activity is regulated by alternative splicing in response to disruptions in endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR) activation. XBP1 interacts with a key signaling component of the highly conserved UPR and is critical in determining cell fate when responding to ER stress in liver diseases. This review aims to elucidate the emerging roles and molecular mechanisms of XBP1 in liver pathogenesis, focusing on its involvement in DILI, viral liver infections, MASLD, fibrosis/cirrhosis, and liver cancer. Understanding the multifaceted functions of XBP1 in these liver diseases offers insights into potential therapeutic strategies to restore ER homeostasis and mitigate liver damage.

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.

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.

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.