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.Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice
Seung Sik YOO ; Yuri KIM ; Dong Won LEE ; Hyeon Joo HAM ; Jung Ho PARK ; In Jun YEO ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2025;33(3):417-428
To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.
3.Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice
Seung Sik YOO ; Yuri KIM ; Dong Won LEE ; Hyeon Joo HAM ; Jung Ho PARK ; In Jun YEO ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2025;33(3):417-428
To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.
4.Risk Factors for the Occurrence of Peripheral Venous Catheter-Related Phlebitis in Hospitalized Patients with Neurosurgery: A Retrospective Study
Yun Hee HONG ; Soon Yeo JOO ; Nam Hee CHAE ; Ji Yoon KIM ; Min-Jung CHOI
Journal of Korean Clinical Nursing Research 2025;31(1):80-90
Purpose:
This study aimed to identify the risk factors for peripheral intravenous catheter-related phlebitis in hospitalized neurosurgery patients.
Methods:
This study involved 443 neurosurgery patients who were admitted to a general hospital in Seoul. The analysis included 982 intravenous lines. Data were retrospectively extracted from electronic medical records for the period between November 1, 2022, and May 31, 2023. Data were analyzed using descriptive statistics, independent t-test, x 2 test, and logistic regression.
Results:
The incidence rate of phlebitis was 13.6%, with the majority of cases classified as grade 2. Gender, present diseases, length of hospital stay, needle gauge size, and cardiovascular drugs were identified as risk factors for phlebitis in neurosurgery patients.
Conclusion
This study is significant as it provides basic data for the prevention and management of peripheral phlebitis in hospitalized neurosurgery patients. The risk factors identified in this study should be incorporated into nursing education to implement a systematic peripheral intravenous management program, and appropriate peripheral intravenous catheter-related nursing interventions are necessary based on the characteristics of each patient.
5.Risk Factors for the Occurrence of Peripheral Venous Catheter-Related Phlebitis in Hospitalized Patients with Neurosurgery: A Retrospective Study
Yun Hee HONG ; Soon Yeo JOO ; Nam Hee CHAE ; Ji Yoon KIM ; Min-Jung CHOI
Journal of Korean Clinical Nursing Research 2025;31(1):80-90
Purpose:
This study aimed to identify the risk factors for peripheral intravenous catheter-related phlebitis in hospitalized neurosurgery patients.
Methods:
This study involved 443 neurosurgery patients who were admitted to a general hospital in Seoul. The analysis included 982 intravenous lines. Data were retrospectively extracted from electronic medical records for the period between November 1, 2022, and May 31, 2023. Data were analyzed using descriptive statistics, independent t-test, x 2 test, and logistic regression.
Results:
The incidence rate of phlebitis was 13.6%, with the majority of cases classified as grade 2. Gender, present diseases, length of hospital stay, needle gauge size, and cardiovascular drugs were identified as risk factors for phlebitis in neurosurgery patients.
Conclusion
This study is significant as it provides basic data for the prevention and management of peripheral phlebitis in hospitalized neurosurgery patients. The risk factors identified in this study should be incorporated into nursing education to implement a systematic peripheral intravenous management program, and appropriate peripheral intravenous catheter-related nursing interventions are necessary based on the characteristics of each patient.
6.Risk Factors for the Occurrence of Peripheral Venous Catheter-Related Phlebitis in Hospitalized Patients with Neurosurgery: A Retrospective Study
Yun Hee HONG ; Soon Yeo JOO ; Nam Hee CHAE ; Ji Yoon KIM ; Min-Jung CHOI
Journal of Korean Clinical Nursing Research 2025;31(1):80-90
Purpose:
This study aimed to identify the risk factors for peripheral intravenous catheter-related phlebitis in hospitalized neurosurgery patients.
Methods:
This study involved 443 neurosurgery patients who were admitted to a general hospital in Seoul. The analysis included 982 intravenous lines. Data were retrospectively extracted from electronic medical records for the period between November 1, 2022, and May 31, 2023. Data were analyzed using descriptive statistics, independent t-test, x 2 test, and logistic regression.
Results:
The incidence rate of phlebitis was 13.6%, with the majority of cases classified as grade 2. Gender, present diseases, length of hospital stay, needle gauge size, and cardiovascular drugs were identified as risk factors for phlebitis in neurosurgery patients.
Conclusion
This study is significant as it provides basic data for the prevention and management of peripheral phlebitis in hospitalized neurosurgery patients. The risk factors identified in this study should be incorporated into nursing education to implement a systematic peripheral intravenous management program, and appropriate peripheral intravenous catheter-related nursing interventions are necessary based on the characteristics of each patient.
7.Risk Factors for the Occurrence of Peripheral Venous Catheter-Related Phlebitis in Hospitalized Patients with Neurosurgery: A Retrospective Study
Yun Hee HONG ; Soon Yeo JOO ; Nam Hee CHAE ; Ji Yoon KIM ; Min-Jung CHOI
Journal of Korean Clinical Nursing Research 2025;31(1):80-90
Purpose:
This study aimed to identify the risk factors for peripheral intravenous catheter-related phlebitis in hospitalized neurosurgery patients.
Methods:
This study involved 443 neurosurgery patients who were admitted to a general hospital in Seoul. The analysis included 982 intravenous lines. Data were retrospectively extracted from electronic medical records for the period between November 1, 2022, and May 31, 2023. Data were analyzed using descriptive statistics, independent t-test, x 2 test, and logistic regression.
Results:
The incidence rate of phlebitis was 13.6%, with the majority of cases classified as grade 2. Gender, present diseases, length of hospital stay, needle gauge size, and cardiovascular drugs were identified as risk factors for phlebitis in neurosurgery patients.
Conclusion
This study is significant as it provides basic data for the prevention and management of peripheral phlebitis in hospitalized neurosurgery patients. The risk factors identified in this study should be incorporated into nursing education to implement a systematic peripheral intravenous management program, and appropriate peripheral intravenous catheter-related nursing interventions are necessary based on the characteristics of each patient.
8.Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice
Seung Sik YOO ; Yuri KIM ; Dong Won LEE ; Hyeon Joo HAM ; Jung Ho PARK ; In Jun YEO ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2025;33(3):417-428
To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.
9.Current Status and Physicians’ Perspectives of Childhood Cancer Survivorship in Korea: A Nationwide Survey of Pediatric Hematologists/ Oncologists
Ji Won LEE ; Yohwan YEO ; Hee Young JU ; Hee Won CHO ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Su-Min JEONG ; Dong Wook SHIN ; Hee Jo BAEK ; Hoon KOOK ; Nack-Gyun CHUNG ; Bin CHO ; Young Ae KIM ; Hyeon Jin PARK ; Yun-Mi SONG
Journal of Korean Medical Science 2023;38(29):e230-
Background:
Data on the status of long-term follow-up (LTFU) care for childhood cancer survivors (CCSs) in Korea is lacking. This study was conducted to evaluate the current status of LTFU care for CCSs and relevant physicians’ perspectives.
Methods:
A nationwide online survey of pediatric hematologists/oncologists in the Republic of Korea was undertaken.
Results:
Overall, 47 of the 74 board-certified Korean pediatric hematologists/oncologists currently providing pediatric hematology/oncology care participated in the survey (response rate = 63.5%). Forty-five of the 47 respondents provided LTFU care for CCSs five years after the completion of primary cancer treatment. However, some of the 45 respondents provided LTFU care only for CCS with late complications or CCSs who requested LTFU care. Twenty of the 45 respondents oversaw LTFU care for adult CCSs, although pediatric hematologists/ oncologists experienced more difficulties managing adult CCSs. Many pediatric hematologists/oncologists did not perform the necessary screening test, although CCSs had risk factors for late complications, mostly because of insurance coverage issues and the lack of Korean LTFU guidelines. Regarding a desirable LTFU care system for CCSs in Korea, 27 of the 46 respondents (58.7%) answered that it is desirable to establish a multidisciplinary CCSs care system in which pediatric hematologists/oncologists and adult physicians cooperate.
Conclusion
The LTFU care system for CCS is underdeveloped in the Republic of Korea. It is urgent to establish an LTFU care system to meet the growing needs of Korean CCSs, which should include Korean CCSs care guidelines, provider education plans, the establishment of multidisciplinary care systems, and a supportive national healthcare policy.
10.Botulinum Toxin A Ameliorates Neuroinflammation in the MPTP and 6-OHDA-Induced Parkinson’s Disease Models
Hyeon Joo HAM ; In Jun YEO ; Seong Hee JEON ; Jun Hyung LIM ; Sung Sik YOO ; Dong Ju SON ; Sung-Su JANG ; Haksup LEE ; Seung-Jin SHIN ; Sang Bae HAN ; Jae Suk YUN ; Jin Tae HONG
Biomolecules & Therapeutics 2022;30(1):90-97
Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

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