To investigate the relationship between symptom of attention-deficit/hyperactivity disorder (ADHD) and allergic rhinitis (AR) in AR children of different genders and ages. Four hundred and sixty-five allergic rhinitis children aged 6–12 years old were recruited in this study. Skin-prick test, Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), Total Nasal Symptoms Score (TNSS) and the Swanson, Nolan, and Pelham version IV scale (SNAP-IV) were recorded. Patients were divided into AR with ADHD and AR without ADHD, according to the SNAP-IV scale results. Children with the inattention/hyperactivity scale (IHS) > 1.25 accounted for 26.4% of all children with AR. The TNSS with IHS > 1.25 group were significantly higher than the IHS ≤ 1.25 group. Univariate analysis showed that age, gender, duration of AR symptoms, skin index, and PRQLQ subscales were associated with symptoms of hyperactivity and attention deficit (IHS > 1.25). After normalizing the age and gender factors, duration of AR symptoms and skin index correlated with IHS > 1.25. After stratifying age and gender, the correlation between IHS > 1.25 and skin index and PRQLQ subscales was mainly found in male children, and the association between the duration of AR symptoms and IHS > 1.25 was reflected in each group. ADHD in children with AR is associated with severity, duration, and skin index of AR, and this association is more pronounced in male children.

Acute lung injury (ALI) is a serious acute respiratory disease that can cause alveolar-capillary barrier disruption and pulmonary edema, respiratory failure and multiple organ dysfunction syndrome. However, there is no effective drugs in clinic until now. GSK3179106 has been reported can alleviate intestinal stress syndrome, but the protective effect of GSK3179106 on ALI has not been elucidated. The present study will evaluate the pharmacological activity of GSK3179106 on lipopolysaccharide (LPS)-induced inflammation and lung injury and clarify its underlying mechanism. We found that GSK3179106 significantly attenuated LPS-induced lung injury in vivo, accompanied by inhibited infiltration of inflammatory cells and reduced expression of inflammatory cytokines. Meanwhile, GSK3179106 dose-dependently reduced the LPS-induced IL-6 expression both in protein and gene levels in macrophages. Mechanistically, GSK3179106 could inhibited the phosphorylation of P38 MAPK induced by LPS. Importantly, results showed that there is a direct combination between GSK3179106 and P38 MAPK. Together, our findings not only clarified the anti-inflammatory activity of GSK3179106 but also discovered its new clinical indications. Therefore, compound GSK3179106 may be a potential candidate for the treatment of acute inflammatory diseases.

Introduction: Group 2 innate lymphoid cells (ILC2s) play a crucial role in house dust mite (HDM)-induced allergic inflammation, and allergen immunotherapy (AIT) holds promise for treating the disease by reducing the frequency of ILC2s. Despite significant progress in AIT for allergic diseases, there remains a need to improve the control of allergic symptoms.Methods: We investigated the synergistic effect of the Notch signaling pathway and subcutaneous immunotherapy (SCIT) in treating allergic airway inflammation in mice and their impact on the ratio of ILC2s in lung tissues. This was achieved by establishing the HDM-induced airway allergic disorders (HAAD) model and SCIT model. Additionally, we conducted in vitro investigations into the effect of the Notch signaling pathway on the secretory function of activated ILC2s using fluorescence-activated cell sorting. Furthermore, we explored the coactivation of the Notch signaling pathway with SCIT in vitro by sorting ILC2s from the lung tissues of mice after SCIT modeling.Results: Previously, our group demonstrated that Notch signaling pathway inhibitors can reduce allergic airway inflammation in mice. Notch signaling induces lineage plasticity of mature ILC2s. In this study, we showed that AIT alleviates allergic airway inflammation and suppresses the frequency of ILC2s induced by HDM. Interestingly, AIT combined with a γ-secretase inhibitor (GSI), an inhibitor of the Notch signaling pathway, significantly inhibited the frequency of ILC2s, reduced airway inflammation, and suppressed Th2-type responses in a mouse model. Furthermore, lung ILC2s from HDM-challenged mice with or without AIT were treated with GSI in vitro, and we found that GSI dramatically reduced the secretion of type 2 inflammatory factors in ILC2s.Discussion: These findings suggest that Notch signaling pathway inhibitors can be used as adjuvant therapy for AIT and may hold potential treatment value in the cooperative control of allergic airway inflammation during early AIT.

Asthma is a prevalent chronic airway disorder characterized by airway hyperresponsiveness (AHR), persistent airway inflammation, and airway remodeling. Emerging evidence implicates ubiquitination‐a critical post‐translational modification‐in asthma pathogenesis. The study identifies ovarian tumor deubiquitinase 6A (OTUD6A), a deubiquitinase with established oncogenic roles, as a novel regulator of airway inflammation and remodeling. The study finds a significantly upregulation of OTUD6A in asthma patients and murine lungs, with predominant localization in airway epithelial cells. Genetic ablation of Otud6a prevents house dust mite (HDM)‐induced AHR, airway inflammation, mucin hypersecretion in both chronic and acute asthma models, as well as airway remodeling in chronic asthma model. Mechanistically, multi‐omics analysis identifies the secreted cytokine human (h)Resistin/mouse resistin‐like molecule α (mRELMα) as a substrate of OTUD6A. OTUD6A deubiquitinates and stabilizes hResistin by specifically removing its K48‐linked polyubiquitin chains at lysines K2 and K19 via the catalytic residue C152, thereby blocking its proteasomal degradation and promoting its secretion. The consequent accumulation of hResistin potentiates epithelial alarms production and facilitates epithelial‐mesenchymal transition, driving airway inflammation and airway remodeling. Furthermore, adeno‐associated virus 6‐mediated OTUD6A silencing in murine lungs markedly ameliorates asthma phenotypes. These findings establish a pathogenic OTUD6A‐hResistin/mRELMα axis and nominating OTUD6A as a promising therapeutic target for asthma intervention.