This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Background: Mass spectrometry (MS) methods exhibit higher accuracy and comparability in measuring serum C-peptide concentrations than immunoassays. We developed and validated a novel isotope dilution-ultraperformance liquid chromatography-tandem MS (IDUPLC-MS/MS) assay to measure serum C-peptide concentrations. Methods: Sample pretreatment involved solid-phase extraction, ion-exchange solid-phase extraction, and derivatization with 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (Cayman Chemical, Ann Arbor, Michigan, USA). We used an ExionLC UPLC system (Sciex, Framingham, MA, USA) and a Sciex Triple Quad 6500 + MS/MS system (Sciex) for electrospray ionization in positive-ion mode with multiple charge states of [M+3H]3+ and multiple reaction monitoring transitions. The total run time was 50 mins, and the flow rate was 0.20 mL/min. We evaluated the precision, trueness, linearity, lower limit of quantitation (LLOQ), carryover, and matrix effects. Method comparison with electrochemiluminescence immunoassay (ECLIA) was performed in 138 clinical specimens. Results: The intra- and inter-run precision coefficients of variation were < 5% and the bias values for trueness were < 4%, which were all acceptable. The verified linear interval was 0.050–15 ng/mL, and the LLOQ was 0.050 ng/mL. No significant carryover or matrix effects were observed. The correlation between this ID-UPLC-MS/MS method and ECLIA was good (R = 0.995, slope = 1.564); however, the ECLIA showed a positive bias (51.8%). Conclusions The developed ID-UPLC-MS/MS assay shows acceptable performance in measuring serum C-peptide concentrations. This will be useful in situations requiring accurate measurement of serum C-peptide in clinical laboratories.

Background: Citrin deficiency is an autosomal recessive disorder caused by pathogenic variants in SLC25A13, presenting with various age-dependent clinical phenotypes and a broad spectrum of severity. However, few studies have examined the frequency and prevalence of citrin deficiency. We aimed to analyze the carrier frequency and disease prevalence in East Asian populations and Koreans. Methods: We comprehensively reviewed the literature and conducted a cross-sectional study to analyze genomic databases, including the Genome Aggregation Database (gnomAD), Korean Variant Archive (KOVA), and Tohoku Medical Megabank Organization (ToMMo), to identify pathogenic SLC25A13 variants in East Asian populations. A founder 3-kilobase (kb) insertion in intron 16 of SLC25A13 was investigated using whole-genome sequencing data from 681 Koreans with the Linux grep command. Results: Twenty-three pathogenic SLC25A13 variants were identified, with c.852_855del being the most common. Analysis of data from 17,501 East Asian individuals in the gnomAD and ToMMo databases revealed a carrier frequency of 1 in 62 people. Analysis of data from 7,214 individuals in the gnomAD and KOVA databases revealed a carrier frequency of 1 in 86, corresponding to an estimated disease prevalence of 1 in 29,502.c.1177+1G > A was identified as the most prevalent pathogenic variant in Koreans. The 3 kb insertion in intron 16 was detected in three out of 681 individuals, indicating a carrier frequency of 1 in 228. Conclusions The high carrier frequency of citrin deficiency in East Asians highlights the need for enhanced genetic screening and counseling, particularly in Korea, providing a valuable reference for future studies on genetic diversity and pathogenic variants in this population.

Background: Humans are exposed to mercury primarily in its highly toxic form, methyl mercury, which is known to have adverse effects on various organs and systems. The negative impact of mercury exposure on the growth, development, and mental health of children, from infancy to adolescence, is well-documented. However, there are no internationally standardized safe limits for mercury exposure. This study investigated the impact of dietary habits and higher body mass index (BMI) on blood mercury levels in adolescents. Methods: This study analyzed the data from the 4th Korean National Environmental Health Survey (KoNEHS) 2018–2020. The focus was on 825 middle and high school students aged 13–18 years, whose blood mercury levels were measured. A survey on dietary and lifestyle habits was also conducted. Blood mercury levels were categorized by geometric median values, and associations with overweight status and seafood consumption were examined using a generalized linear model. Results: The geometric mean blood mercury level for the entire sample was 1.37 μg/L, with levels of 1.31 μg/L in normal-weight individuals and 1.43 μg/L in overweight individuals, showing a statistically significant difference between the two groups. After adjusting for other variables, blood mercury levels were significantly associated with overweight status (estimate: 0.084; p = 0.018; 95% confidence interval [CI]: 0.015–0.153), consumption of large fish and tuna more than once a week (estimate: 0.18; p = 0.001; 95% CI: 0.077–0.284), and consumption of fish once a week or more (estimate: 0.147; p = 0.004; 95% CI: 0.043–0.250). Conclusions In adolescents, a higher BMI and an increased consumption of large fish, tuna, and fish were associated with higher blood mercury levels. Notably, a stronger association was found between large fish consumption and blood mercury levels in the overweight group. These findings suggest the need to moderate seafood consumption and establish more proactive mercury exposure standards for adolescents.

Purpose: This study aimed to characterize the clinical patterns and severity of brain injury in neonates who survived extracorporeal membrane oxygenation (ECMO) therapy for acute respiratory failure during the neonatal period, to evaluate their short-term neurodevelopmental outcomes, and to identify the factors associated with these outcomes. Methods: We retrospectively reviewed the medical records of neonates who survived ECMO between 2018 and 2024. Based on brain magnetic resonance imaging (MRI) findings, the patients were classified into two groups: no/mild and moderate/severe brain injury. Neurodevelopmental outcomes were assessed at 12–40 months of age using the Bayley Scale of Infant Development II/III and/or the Korean Developmental Screening Test. Results: Among the 19 neonates included in the study, 18 (94.7%) showed varying degrees of brain injury on MRI (mild: 12, moderate: 1, severe: 5). Neonates with moderate/severe brain injury had significantly longer durations of ECMO support and extended durations of mechanical ventilation and were more likely to receive continuous renal replacement therapy than those with no or mild injury. Developmental delay was identified in 36.8% of survivors and was significantly associated with prolonged mechanical ventilation, longer neonatal intensive care unit stays, and a higher incidence of seizures. Conclusion Brain injury is frequently observed on MRI in neonates treated with ECMO. However, its direct association with adverse neurodevelopmental outcomes is not definitive. Since MRI findings alone cannot predict developmental outcomes, clinical and environmental factors should be integrated into prognostic assessments.

Purpose: Congenital hypothyroidism (CH) is a major preventable cause of intellectual disability, particularly in very low birth weight (VLBW) infants, who are at increased risk due to hypothalamic-pituitary-thyroid axis immaturity. Early differentiation between transient CH (TCH) and permanent CH (PCH) is crucial to optimize L-thyroxine (LT4) treatment duration. This study aimed to determine the incidence of PCH among Korean VLBW infants and to identify clinical factors that may aid in distinguishing TCH from PCH. Methods: This retrospective cohort study included VLBW infants diagnosed with CH and treated with LT4 at a single tertiary neonatal intensive care unit between 2011 and 2020. Infants requiring LT4 beyond 3 years were classified as PCH, while those who discontinued earlier were considered TCH. Clinical characteristics, neonatal morbidities, and thyroid-related parameters were compared between the groups. Results: Among 1,292 VLBW infants, 122 (9.4%) were diagnosed with CH. After excluding deaths and those lost to follow-up, 73 infants were included in the final analysis (TCH, n=50; PCH, n=23). The PCH group had a significantly higher mean gestational age and greater LT4 requirements at both 12 and 36 months of age. Major anomalies were more frequently observed in PCH infants, including congenital heart defects. In multivariate analysis, higher gestational age, the presence of major anomalies, screening thyroid-stimulating hormone (TSH) >10 μIU/mL, and higher LT4 dose at 36 months were significantly associated with PCH. Conclusion The incidence of PCH in Korean VLBW infants was relatively higher than that reported in previous studies studies. Screening TSH level and LT4 dose requirements may support individualized follow-up and help distinguish PCH from TCH.

Objectives: To assess the trends and disparities in the utilization of F-18 fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) in Korea between 2018 and 2022, with a focus on disease classification, patient demographics, and regional distribution. Methods: This national surveillance retrospective study uses data from the Health Insurance Review and Assessment Service (HIRA) database, which includes all FDG PET/CT examinations conducted in Korea from 2018 to 2022. Disease classifications, cancer types, age groups, gender, and geographic regions were analyzed using descriptive statistics. Utilization rates per 100,000 population were calculated for regional comparisons. Results: FDG PET/CT utilization increased by 25.4%, from 174,885 examinations in 2018 to 219,377 in 2022. Older age groups (60 years and above) accounted for the majority of examinations, with males undergoing more examinations than females. Oncology remained the primary indication, with lung, colorectal, and non-Hodgkin lymphoma leading in examination numbers. The number of examinations performed on patients aged 60 and above increased at a higher rate compared to those under 60. Significant geographic disparities were found, with Seoul reporting the highest utilization rate (1,114.3 examinations per 100,000 population), while Gyeongbuk exhibited much lower rate (26.2 examinations per 100,000 population). Conclusions This study highlights the growing utilization of FDG PET/CT in Korea, particularly among older adults, with significant gender differences in cancer types. The findings also reveal disparities in FDG PET/CT utilization across regions, indicating varying access to advanced imaging technology.

Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8+ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8+ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.

Objective: Previous studies have reported an association between cancer-related symptoms and perceived social support (PSS). The objective of this study was to analyze whether Chemotherapy-Induced Peripheral Neuropathy (CIPN), a prevalent side effect of chemotherapy, varies according to PSS level using a validated tool for CIPN at prospective follow-up. Methods: A total of 39 breast cancer patients were evaluated for PSS using the Multidimensional Scale of Perceived Social Support (MSPSS) prior to chemotherapy and were subsequently grouped into one of two categories for each subscale: low-to-moderate PSS and high PSS. CIPN was prospectively evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) at five time points. A linear mixed-effects model with square root transformation was employed to investigate whether the CIPN20 scales varied by PSS level and time point. Results: Statistical analysis of the MSPSS total scale and subscales revealed a significant effect of the friends subscale group and time point on the CIPN20 sensory scale. The sensory scale score of CIPN20 was found to be lower in participants with high PSS from friends in comparison to those with low-to-moderate PSS at 1 month post-chemotherapy (p=0.010). Conclusion This is the first study to prospectively follow the long-term effect of pre-treatment PSS from friends on CIPN. Further studies based on larger samples are required to analyze the effects of PSS on the pathophysiology of CIPN.