This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Transcription factor CP2-like protein 1 (Tfcp2l1), a naïve pluripotency transcription factor, is expressed in both early embryonic and adult tissues, where it enforces pluripotency of embryonic stem cells (ESCs) and stemness features of cancer cells, respectively. However, the detailed molecular pathways by which Tfcp2l1 is regulated in early embryonic development and cancer cells remain unknown. Here, we identified the pseudophosphatase dual specificity phosphatase 27 (Dusp27), also known as serine/threonine/tyrosine-interacting like-2, as a novel Tfcp2l1-interacting protein through a sterile alpha motif-like domain in the C-terminus of Tfcp2l1 in murine ESCs. The interaction between Dusp27 and Tfcp2l1 was dependent on the cell cycle status and increased during mitosis. Expression of Dusp27 was upregulated during naïve pluripotency and repressed during spontaneous differentiation of murine ESCs. Ectopic expression of Dusp27 enhanced the transcriptional activity of Tfcp2l1 and promoted features associated with the naïve pluripotent state, while suppressing meso-endodermal lineage differentiation. The present study demonstrates that Dusp27 is a novel positive regulator of Tfcp2l1 through a physical interaction and thereby fine-tunes the pluripotency status and meso-endodermal differentiation of murine ESCs.

Purpose: The clinical characteristics of headaches vary by age among pediatric patients. Red flag signs are key factors in differentiating secondary headaches and should be considered in the context of the patient’s age. Methods: This study involved a retrospective chart review of pediatric patients presenting with headaches. Patients were categorized by age into three groups: pre-school age (under 6 years), school-age (6 to 12 years), and adolescence (over 12 years). Demographic data, headache characteristics, laboratory findings, and neuroimaging results were evaluated. Overall, 17 potential red flags were assessed. Results: A total of 687 patients were included, of whom 102 were of pre-school age, 314 were school-aged, and 271 were adolescents. The frequency of overweight/obesity was found to increase with age. The pre-school age group experienced a shorter period from symptom onset to presentation and a briefer duration of pain. In contrast, adolescents displayed a longer period from symptom onset, a greater frequency of headaches occurring at least three times per week, and a higher rate of headache episodes lasting over 3 days. Children under 6 years old were more commonly diagnosed with secondary headaches than older children. Across age groups, secondary headaches were suspected when systemic symptoms such as fever were present, when the headache had a sudden onset, when the patient responded poorly to medication, or when abnormal neurological signs and symptoms were observed. Conclusion The clinical features of pediatric patients vary by age group. Clinicians should consider red flag signs in the context of patient age and individual characteristics.

Purpose: Suicide ranks among the top causes of death among youth in South Korea. This study aimed to identify the characteristics of suicidal individuals treated at emergency departments between 2011 and 2020. Methods: A retrospective analysis was conducted using data from January 2011 to December 2020 in the Injury Surveillance Cohort, a prospective registry. Patients’ sex, age, mortality, methods of self-harm, and previous suicide attempts were analyzed. The methods of self-harm were categorized into falls, asphyxiation, blunt injuries, penetrating injuries, poisoning, and others. Sub-groups with and without poisoning were compared. Results: The proportion of self-harm/suicide attempts increased from 2.3% (2011) to 5.0% (2020). The mortality rate decreased from 10.8% (2011) to 6.3% (2020). Poisoning was the most common method (61.7%). Mortality rates ranged from 42.0% for asphyxiation to 0.2% for blunt injuries. Individuals in their 20s showed a marked increase in suicide/self-harm attempts, especially in the last three years. A large proportion of decedents in their 70s or older (52.6%) used poisoning as a method of suicide. The percentage of individuals with two or more previous attempts rose from 7.1% (2011) to 19.7% (2020). The death rates by poisoning decreased from 7.7% (2011) to 2.5% (2020). Conclusion Our findings underscore the urgent need for targeted interventions and suicide prevention policies. Managing and reducing suicide and self-harm in emergency settings will require a focus on poisoning, the 10–29 age group, and the elderly. This paper will be valuable for future policies aiming to reduce the societal burden of suicide and self-harm.