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"Won Jae Kim"
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Beauty looks down on me : stories
\"Beauty Despises Me is a collection of by turns sad and funny stories about the thwarted expectations of the young as they grow older. HeeKyung's characters are misfits who by virtue of their bodies or their lack of social status are left to dream of momentous changes that will never come. Unsatisfied with work, with family, with friends, they lose themselves in diets, books, and blogs. Heekyung's collection humorously but humanely depicts the loneliness and monotony found in many modern lives.\"-- Provided by publisher
Book
Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-κB Suppression and Nrf-2/HO-1 Activation
Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases. Microglia are the primary neuroimmune cells that play a crucial role in cerebral inflammation. Epigallocatechin gallate (EGCG) has a protective antioxidant and anti-inflammatory effects against neuroinflammation. However, the effects of EGCG on hypoxia-induced inflammation in microglia and the underlying mechanism remain unclear. In this study, we investigated whether EGCG might have a protective effect against hypoxia injury in microglia by treatment with CoCl2 to establish a hypoxic model of BV2 microglia cells following EGCG pre-treatment. An exposure of cells to CoCl2 caused an increase in inflammatory mediator interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 expression, which were significantly ameliorated by EGCG via inhibition of NF-κB pathway. In addition, EGCG attenuated the expression of hypoxia-inducible factor (HIF)-1α and the generation of ROS in hypoxic BV2 cells. Furthermore, the suppression of hypoxia-induced IL-6 production by EGCG was mediated via the inhibition of HIF-1α expression and the suppression of ROS generation in BV2 cells. Notably, EGCG increased the Nrf-2 levels and HO-1 levels in the presence of CoCl2. Additionally, EGCG suppressed hypoxia-induced apoptosis of BV2 microglia with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3. In summary, EGCG protects microglia from hypoxia-induced inflammation and oxidative stress via abrogating the NF-κB pathway as well as activating the Nrf-2/HO-1 pathway.
Journal Article
Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer
Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.
Caveolin-1: Survival Mechanism in Gastric Cancer Cells
A new study reveals that Caveolin-1 (CAV1) is specifically expressed in the most malignant SEM-type gastric cancer (GC), and CAV1-driven endocytosis is a critical survival mechanism of malignant GC. Researchers found that chloroquine (CQ), an anti-malarial drug known to block endocytosis, effectively induced cell death in CAV1-positive SEM-type GC cells by impairing lysosomal activity and extracellular nutrient uptake. In patient-derived organoids and mouse models, CQ treatment significantly reduced tumor growth and improved survival rates, suggesting its potential as a therapeutic alternative for chemo-resistant SEM-type GC patients. The study highlights the importance of targeting endocytosis in cancer treatment and provides new insights into the development of personalized therapies for GC patients.
Journal Article
Predicting Methylphenidate Response in ADHD Using Machine Learning Approaches
Background:There are no objective, biological markers that can robustly predict methylphenidate response in attention deficit hyperactivity disorder. This study aimed to examine whether applying machine learning approaches to pretreatment demographic, clinical questionnaire, environmental, neuropsychological, neuroimaging, and genetic information can predict therapeutic response following methylphenidate administration.Methods:The present study included 83 attention deficit hyperactivity disorder youth. At baseline, parents completed the ADHD Rating Scale-IV and Disruptive Behavior Disorder rating scale, and participants undertook the continuous performance test, Stroop color word test, and resting-state functional MRI scans. The dopamine transporter gene, dopamine D4 receptor gene, alpha-2A adrenergic receptor gene (ADRA2A) and norepinephrine transporter gene polymorphisms, and blood lead and urine cotinine levels were also measured. The participants were enrolled in an 8-week, open-label trial of methylphenidate. Four different machine learning algorithms were used for data analysis.Results:Support vector machine classification accuracy was 84.6% (area under receiver operating characteristic curve 0.84) for predicting methylphenidate response. The age, weight, ADRA2A MspI and DraI polymorphisms, lead level, Stroop color word test performance, and oppositional symptoms of Disruptive Behavior Disorder rating scale were identified as the most differentiating subset of features.Conclusions:Our results provide preliminary support to the translational development of support vector machine as an informative method that can assist in predicting treatment response in attention deficit hyperactivity disorder, though further work is required to provide enhanced levels of classification performance.
Journal Article
The impact of negative emotions on adolescents’ nonsuicidal self-injury thoughts: an integrated application of machine learning and multilevel logistic models
Non-Suicidal Self-Injury (NSSI) is a prevalent and complex behavior among adolescents, often linked to negative emotions such as loneliness, anxiety, and emptiness. Traditional self-report and experimental methods rely on autobiographical recall and are therefore vulnerable to bias and low ecological validity. Accordingly, approaches that repeatedly sample NSSI-related feelings and contexts in daily life such as Ecological Momentary Assessment (EMA) are needed. This study aimed to identify emotional predictors of NSSI thoughts among adolescents using machine learning and multilevel logistic regression. The study included 42 adolescents (aged 12–15 years) who had engaged in NSSI in the past year. Participants reported their mood and NSSI behaviors three times daily over a 14-day EMA period via a smartphone application. Predictor variables included depression, anxiety, loneliness, self-anger, anger towards others, shame, and emptiness. A random forest model identified loneliness (feature importance: 0.40), anxiety (0.18), and emptiness (0.14) as the most significant predictors of NSSI thoughts. Multilevel logistic regression confirmed these findings, showing that each one-unit increase in anxiety, loneliness, and emptiness corresponded to a 24%, 19%, and 24% increase in the odds of experiencing NSSI thoughts, respectively. The ICC value of 0.26 indicated substantial between-individual variance, justifying multilevel modeling. However, random effects analysis revealed no significant individual differences, suggesting uniform effects across participants. These findings highlight loneliness as the most influential predictor, emphasizing the need to address social connections in interventions. Combining machine learning with traditional statistical methods enhanced interpretability, providing practical insights for developing tailored, emotion-focused interventions for adolescents engaging in NSSI.
Journal Article
Development and validation of the Self-Harm Screening Inventory (SHSI) for adolescents
Despite the rapidly increasing rate of non-suicidal self-injury (NSSI) among adolescents, there is a dearth of culturally appropriate psychological measures screening for NSSI among the adolescents in the Asian countries. This study aimed to develop and validate the Self-Harm Screening Inventory (SHSI), a culturally sensitive and suitable scale for screening adolescents for NSSI. In total, 514 Korean adolescents (aged 12–16 years) were recruited nationwide. All participants gave informed consent and completed the online self-report measures on NSSI, depression, anxiety, and self-esteem. Thereafter, preliminary items were developed through a series of steps: literature review, ratings of experts on self-harm and suicide, and statistical analyses. Ten of the 20 preliminary items were eliminated after exploratory factor analysis due to low endorsement and factor loading (less than .70). The final version of the SHSI comprised 10 binary items relating to self-harm behaviors within the past year (e.g., cut my body with sharp objects, hit my body). A confirmatory factor analysis supported a one-factor structure, as hypothesized. The one-factor model had a good model fit ( x 2 (35) = 84.958, p < .001, RMSEA = .053, CFI = .981, TLI = .975, SRMR = .124). The SHSI also had good internal consistency (Cronbach’s alpha = .795) and 4-week test-retest reliability ( r = .786, p < .01). The SHSI had high correlations with another self-harm related scale, the Self-Harm Inventory ( r = .773, p < .01), and moderate correlations with the Child Depression Inventory ( r = .484, p < .01) and Revised Children’s Manifest Anxiety Scale ( r = .433, p < .01). Additionally, the SHSI was negatively correlated with the Rosenberg Self-Esteem Scale ( r = -.399, p < .01). The findings indicate that the SHSI is a reliable and valid measure for the screening of self-harm behaviors among adolescents.
Journal Article
The mediating role of internalizing and externalizing symptoms in the relationship between childhood trauma and suicidality among adolescents: a structural equation model
Background
The objective of this study is to investigate the direct and indirect effects of childhood trauma, internalizing symptoms, and externalizing symptoms on suicidality among adolescents, thereby establishing a structural equation model.
Methods
The present study uses a cross-sectional descriptive design. Among 147 adolescents aged 12–17, 93 outpatients diagnosed with major depressive disorder and 54 controls were included in the study. They completed the Early Trauma Inventory Self-Report (Short Form) and Columbia Suicidality Severity Rating Scale. Their parents completed the Child Behavior Checklist. Analyses were performed using Pearson’s correlation and structural equation modelling.
Results
Childhood trauma had both direct and indirect effects, via internalizing symptoms and externalizing symptoms, on suicidality. Internalizing symptoms had a direct effect on suicidality. Meanwhile, externalizing symptoms were not directly associated with suicidality, but indirectly associated via internalizing symptoms.
Conclusions
Findings provide in-depth understanding of the mediating role of internalizing symptoms and externalizing symptoms in the relationship between childhood trauma and suicidality, suggesting that the therapeutic interventions for both internalizing symptoms and externalizing symptoms may be important to prevent suicide in adolescents with childhood trauma.
Journal Article
Decreased Functional Brain Connectivity in Adolescents with Internet Addiction
Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry.
Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures.
Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio.
Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology.
Journal Article
Depression and posttraumatic stress disorder in adolescents with nonsuicidal self-injury: comparisons of the psychological correlates and suicidal presentations across diagnostic subgroups
Background
Nonsuicidal self-injury (NSSI) combined with suicide ideation increases the risk of suicidal behaviors. Depression and posttraumatic stress disorder (PTSD) are comorbidities of NSSI compounding this relationship. The present study compared diagnostic subgroups of NSSI based on current depression and PTSD on psychological correlates (i.e., vulnerabilities and impairment) and suicidal presentations (i.e., suicidal cognitions and behaviors) in a psychiatric sample of adolescents.
Methods
Eighty-seven adolescents meeting DSM-5 criteria for NSSI and 104 age-range-matched nonclinical controls (NC) participated. Participants completed self-report measures on psychological vulnerabilities and impairment (e.g., emotion regulation difficulties, negative cognitions). Adolescents with NSSI also completed clinical interviews on psychiatric diagnoses and a recent self-injurious behavior (SIB). Scores on the psychological correlates of NSSI were compared between adolescents with NSSI and NC, and across three diagnostic subgroups of NSSI (A: NSSI+/depression-/PTSD-,
n
= 14; B: NSSI+/depression+/PTSD-,
n
= 57; C: NSSI+/depression+/PTSD+,
n
= 14). Differences between NSSI diagnostic subgroups were tested on the motives for SIB and accompanying suicidal presentations (e.g., desire, intent, motive, lethality).
Results
Common comorbidities of NSSI included depression, panic disorder, generalized anxiety disorder, and PTSD. The NSSI subgroup classification was significantly associated with panic disorder, which was controlled for in the subsequent group comparisons. Overall, adolescents who engage in NSSI with vs. without depression reported more psychological vulnerabilities and impairment and a greater degree of suicidal thoughts/desire in SIB (i.e., groups B, C >A), which remained significant after controlling for panic disorder. An increased odds of the suicidal motive for SIB was found in adolescents with all three conditions (i.e., group C: NSSI+/depression+/PTSD+) compared to those with NSSI but neither depression nor PTSD (i.e., group A: NSSI+/depression-/PTSD-); however, this was not significant after controlling for panic disorder.
Conclusions
Psychological underpinnings of adolescent NSSI in clinical contexts may be largely associated with concurrent depression. Suicidal motives in adolescents who engage in NSSI in the presence of depression and PTSD may be confounded by the co-occurrence of panic disorder. This study warrants the importance of attending to the comorbid depression with NSSI in adolescents as it is related to an increase in suicidal desire accompanying SIB.
Journal Article
Interaction between lead and noradrenergic genotypes affects neurocognitive functions in attention-deficit/hyperactivity disorder: a case control study
Background
Lead is known to be associated with attention-deficit/hyperactivity disorder (ADHD) even at low concentrations. We aimed to evaluate neurocognitive functions associated with lead in the blood and the interactions between lead and dopaminergic or noradrenergic pathway-related genotypes in youths with ADHD.
Methods
A total of 259 youths with ADHD and 96 healthy controls (aged 5–18 years) enrolled in this study. The Korean Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime version was conducted for psychiatric diagnostic evaluation. Blood lead levels were measured, and their interaction with dopaminergic or noradrenergic genotypes for ADHD; namely, the dopamine transporter (
DAT1
), dopamine receptor D4 (
DRD4
), and alpha-2A-adrenergic receptor (
ADRA2A
) genotypes were investigated. All participants were assessed using the ADHD Rating Scale-IV (ADHD-RS). Participants also completed the continuous performance test (CPT) and Stroop Color-Word Test (SCWT). Analysis of covariance was used for comparison of blood lead levels between ADHD and control groups. A multivariable linear regression model was used to evaluate the associations of blood lead levels with the results of ADHD-RS, CPT, and SCWT; adjusted for intelligence quotient (IQ), age, and sex. A path analysis model was used to identify the mediating effects of neurocognitive functions on the effects of blood lead on ADHD symptoms. To evaluate the effect of the interaction between blood lead and genes on neuropsychological functions, hierarchical regression analyses were performed.
Results
There was a significant difference in blood lead levels between the ADHD and control groups (1.4 ± 0.5 vs. 1.3 ± 0.5 μg/dL,
p
= .005). Blood lead levels showed a positive correlation with scores on omission errors(r = .158,
p
= .003) and response time variability (r = .136,
p
= .010) of CPT. In the multivariable linear regression model, blood lead levels were associated with omission errors (B = 3.748,
p
= .045). Regarding the effects of lead on ADHD symptoms, hyperactivity-impulsivity was mediated by omission errors. An interaction effect was detected between
ADRA2A
DraI genotype and lead levels on omission errors (B = 5.066,
p
= .041).
Conclusions
Our results indicate that neurocognitive functions at least partly mediate the association between blood lead levels and ADHD symptoms, and that neurocognitive functions are affected by the interaction between blood lead levels and noradrenergic genotype.
Journal Article