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Background: The dosage of ovalbumin (OVA) during the sensitization stage is considered a crucial factor in the development of airway hyperresponsiveness (AHR). However, the inconsistent dosages of sensitizing OVA used in current studies and the lack of research on their impact on AHR are notable limitations. Methods: We examined the impact of increasing sensitizing doses of OVA in a murine asthma model, which entailed initial sensitization with OVA followed by repeated exposure to OVA aerosols. BALB/c mice were primed with doses of OVA (0, 10, 20, 50, and 100 μg) plus 1 mg Alum on Days 0 and 7, and were challenged with OVA aerosols (10 mg/mL for 30 min) between Days 14 and 17. Antigen‐induced AHR to methacholine (MCh), as well as histological changes, eosinophilic infiltration, and epithelial injury were assessed. Results: The result indicated that there are striking OVA dose‐related differences in antigen‐induced AHR to MCh. The most intense antigen‐induced AHR to MCh was observed with sensitization at 50 μg, while weaker responses were seen at 10, 20, and 100 μg. Meanwhile, there was a significant increase in eosinophil count with sensitization at 50 μg. The changes of AHR were correlated with total cells count, lymphocytes count, eosinophils count, and basophils count in bronchoalveolar lavage fluid; however, it did not correlate with histological changes such as cellular infiltration into bronchovascular bundles and goblet cell hyperplasia of the bronchial epithelium. Conclusion: Overall, this study demonstrated that sensitization with 50 μg of OVA resulted in the most significant AHR compared to other dosages. These findings may offer valuable insights for future research on mouse asthma modeling protocols. [ABSTRACT FROM AUTHOR]

Background: Diterpene ginkgolides meglumine injection (DGMI) is a platelet‐activating factor receptor (PAFR) antagonist that can be used to treat acute ischemic stroke (AIS). This study evaluated the efficacy and safety of an intensive antiplatelet strategy based on PAFR antagonists and explored the underlying mechanisms of PAFR antagonists in AIS treatment. Methods: This is a retrospective study applying propensity score methods to match AIS patients treated with DGMI to nontreated patients. The primary outcome was functional independence (modified Rankin Scale [mRS] 0–2) at 90 days. The safety outcome was bleeding risk. We used McNemar test to compare the efficacy outcome. Subsequently, the network pharmacology analysis was performed. Results: 161 AIS patients treated with DGMI in the study were matched with 161 untreated patients. Compared with untreated patients, DGMI‐treated patients had a significantly higher rate of mRS ranking 0–2 at 90 days (82.0% vs. 75.8%, p < 0.001), without increased risk of bleeding. The gene enrichment analysis showed that the overlap genes of DGMI targeted and AIS‐related enriched in thrombosis and inflammatory‐related signaling pathways. Conclusions: An intensive antiplatelet strategy of DGMI plus traditional antiplatelet agents is effective in treating AIS and may work by mediating post‐stroke inflammation and thrombosis. [ABSTRACT FROM AUTHOR]

Aims This study explored sFasL expression in neurons and the potential role of neuronal sFasL in modulating the microglial phenotypes. Methods In vivo, middle cerebral artery occlusion ( MCAO) was induced in both FasL-mutant ( gld) and wild-type (wt) mice. In vitro, primary cortical neuron or microglia or coculture from wt/ gld mice was subjected to oxygen glucose deprivation ( OGD). sFasL level in the supernatant was evaluated by ELISA. Neuronal-conditioned medium (NCM) or exogenous sFasL was applied to primary microglia with or without FasL neutralizing antibody. Protein expression of JAK2/ STAT3 and NF-κB pathways were determined by Western blot. The effect of microglia phenotype from wt/ gld mice on the fate of ischemic neurons was further elucidated. Results In vivo, compared with wild-type mice, M1 markers ( CD16, CD32 and iNOS) were attenuated in gld mice after MCAO. In vitro, post- OGD neuron released more sFasL. Both post- OGD NCM and exogenous sFasL could trigger M1-microglial polarization. However, this M1 phenotype shift was partially blocked by utilization of FasL neutralizing antibody or gld NCM. Consistently, JAK2/ STAT3 and NF-κB signal pathways were both activated in microglia after exogenous sFasL treatment. Compared with wild-type mice, M1-conditioned medium prepared from gld mice protected neuron against OGD injury. Conclusions Ischemic neurons release sFasL, which contributes to M1-microglial polarization. The underlying mechanisms may involve the activation of JAK2/ STAT3 and NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]