Cardiac ischemia/reperfusion (I/R) injury is a complicated pathological event, which has close association with pyroptosis. This study uncovered the regulatory mechanisms of fat mass and obesity-associated protein (FTO) in NLRP3-mediated pyroptosis during cardiac I/R injury. H9c2 cells were stimulated with oxygenglucose deprivation/reoxygenation (OGD/R). Cell viability and pyroptosis were detected by CCK-8 and flow cytometry. Western blotting or RT-qPCR was performed to analyze target molecule expression. NLRP3 and Caspase-1 expression was observed by immunofluorescence staining. IL-18 and IL-1β production was detected by ELISA. The total m6A and m6A level of CBL was determined by dot blot assay and methylated RNA immunoprecipitation-qPCR, respectively. The interaction between IGF2BP3 and CBL mRNA was confirmed by RNA pull-down and RIP assays. The protein interaction between CBL and βcatenin and βcatenin ubiquitination were evaluated by Co-IP. Myocardial I/R model was established in rats. We determined infarct size by TTC staining and pathological changes by H&E staining. LDH, CK-MB, LVFS, and LVEF were also assessed. FTO and βcatenin were down-regulated, while CBL was up-regulated by OGD/R stimulation. FTO/β-catenin overexpression or CBL silencing restrained OGD/R-induced NLRP3 inflammasome-mediated pyroptosis. CBL repressed βcatenin expression via ubiquitination and degradation. FTO reduced the mRNA stability of CBL by inhibiting m6A modification. CBL-mediated ubiquitination and degradation of βcatenin were involved in FTO-induced pyroptosis inhibition during myocardial I/R injury. FTO inhibits NLRP3-mediated pyroptosis to attenuate myocardial I/R injury via repressing CBL-induced ubiquitination degradation of βcatenin.

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Atherosclerosis and its complications constitute some of the major diseases affecting humans worldwide. A core component of atherogenesis is endothelial cell damage and dysfunction, which also includes factors such as adhesion and proliferation of various cells. Multiple studies have shown that atherosclerosis and cancer share a common pathophysiological process and exhibit a degree of similarity. Sparcl-1 is a cysteine-rich secretory stromal cell protein present in the extracellular matrix and belongs to the Sparc family of proteins. Its role in tumor development has been widely investigated; however, its role in cardiovascular diseases has rarely been studied. Sparcl-1 is considered an oncogene correlated with the regulation of cell adhesion, migration, and proliferation and is also related to blood vessel integrity. In this review, the potential link between Sparcl-1 and atherosclerosis development is investigated, and recommendations on future research on the role of Sparcl-1 in atherogenesis are provided.

The bed nuclei of the stria terminalis (BST) is recognised as a pivotal integrative centre for monitoring emotional valence. It is implicated in the regulation of diverse affective states and motivated behaviours, and decades of research have firmly established its critical role in anxiety‐related behavioural processes. Researchers have recently intricately dissected the BST's dynamic activities, its connection patterns and its functions with respect to specific cell types using multiple techniques such as optogenetics, in vivo calcium imaging and transgenic tools to unmask the complex circuitry mechanisms that underlie anxiety. In this review, we principally focus on studies of anxiety‐involved neuromodulators within the BST and provide a comprehensive architecture of the anxiety network—highlighting the BST as a key hub in orchestrating anxiety‐like behaviour. We posit that these promising efforts will contribute to the identification of an accurate roadmap for future treatment of anxiety disorders.