interferon regulatory factor (irF) 2 is a transcription factor belonging to the irF family, which is essential for gasdermin d (GSdMd)-induced pyroptosis. decreasing myocardial cell pyroptosis confers protection against heart damage and cardiac dysfunction caused by myocardial infarction (Mi). The aim of the present study was to investigate the involvement of irF2 in Mi and the underlying mechanism of irF2 in pyroptosis. To mimic Mi, ligation of the left anterior descending coronary artery was performed to establish an in vivo mouse model and rat cardiomyocytes H9c2 cells were cultured under hypoxic conditions to establish an in vitro model. Transthoracic echocardiography was used to assess cardiac function. Hematoxylin and eosin staining was used to observe histopathological changes in the myocardial tissue. immunohistochemistry and western blotting were performed to detect irF2 expression levels. Tunel staining and flow cytometry were used to detect apoptosis in myocardial tissue and cells. chromatin immunoprecipitation and dual luciferase reporter assay were used to verify the effect of irF2 on GSdMd transcription. irF2 was upregulated in Mi mice. Mi induced pyroptosis, as evidenced by increased GSdMd, n-terminal GSdMd (GSdMd-n), and cleaved (c-) caspase-1 levels. Mi increased il-1β and il-18 levels. These alterations were alleviated by irF2 silencing. Furthermore, in hypoxia-treated H9c2 cells, IRF2 silencing significantly decreased the elevated levels of il-1β and il-18 and pyroptosis-associated proteins, including GSdMd, GSdMd-n and c-caspase1. Moreover, in hypoxia-treated H9c2 cells, irF2 directly bound to the GSdMd promoter to drive GSdMd transcription and promote pyroptosis and irF2 expression may be regulated via the hypoxia inducible factor 1 signaling pathway. in conclusion, the present results demonstrated that irF2 is a key regulator of Mi by mediating pyroptosis, which triggers GSdMd activation.

Background: Identification of genomic markers using NGS (next generation sequencing) technology would be valuable for guiding precision medicine treatments for pancreatic cancers. Traditional somatic mutation methods require both tumor and matched non-tumor samples. However, only tumor samples are available in most times, especially in retrospective studies. In this study, we tried to analyze the associations between clinical features and oncogenic somatic mutations in genome-wide from tumor-only samples. Method: 54 tumor-only samples derived from pancreatic cancer patients were used for whole-exome sequencing. An approach involving SNP filtering of variants included in Catalogue of Somatic Mutations in Cancer (COSMIC) database was used to identify oncogenic somatic mutations. The relationships between oncogenic mutations and clinical features were analyzed and simultaneously compared with those from the TCGA database. Results: By analyzing the mutations from tumor only samples, divergent mutation profiles were observed in different locations (head vs body/tail) of pancreatic tumors. The divergences between pancreatic head and body/tail cancers were also confirmed by the TCGA data. Furthermore, mutations of several genes were found significantly associated with clinical features, such as pathological stage and the degree of tumor differentiation. Conclusion: The results confirmed the efficiency of our approach for identifying oncogenic somatic mutations from tumor only samples and revealed the associations between somatic mutations and clinical features in pancreatic cancer.