Kawasaki disease (KD) is the most common cause of pediatric cardiac disease in developed countries, and can lead to permanent coronary artery damage and long term sequelae such as coronary artery aneurysms. Given the prevalence and severity of KD, further research is warranted on its pathophysiology. It is known that endothelial cell damage and inflammation are two essential processes resulting in the coronary endothelial dysfunction in KD. However, detailed mechanisms are largely unknown. In this study, we investigated the role of pyroptosis in the setting of KD, and hypothesized that pyroptosis may play a central role in its pathophysiology. In vivo experiments of patients with KD demonstrated that serum levels of pyroptosis-related proteins, including ASC, caspase-1, IL-1β, IL-18, GSDMD and lactic dehydrogenase (LDH), were significantly increased in KD compared with healthy controls (HCs). Moreover, western blot analysis showed that the expression of GSDMD and mature IL-1β was notably elevated in KD sera. In vitro, exposure of human umbilical vein endothelial cells (HUVECs) to KD sera-treated THP1 cells resulted in the activation of NLRP3 inflammasome and subsequent pyroptosis induction, as evidenced by elevated expression of caspase-1, GSDMD, cleaved p30 form of GSDMD, IL-1β and IL-18, and increased LDH release and TUNEL and propidium iodide (PI)-positive cells. Furthermore, our results showed that NLRP3-dependent endothelial cell pyroptosis was activated by HMGB1/RAGE/cathepsin B signaling. These findings were also recapitulated in a mouse model of KD induced by Candida albicans cell wall extracts (CAWS). Together, our findings suggest that endothelial cell pyroptosis may play a significant role in coronary endothelial damage in KD, providing novel evidence that further elucidates its pathophysiology.

Peripheral nerve injury is a major clinical problem and often results in a poor functional recovery. Despite obvious clinical need, treatment strategies have been largely suboptimal. In the nervous system, exosomes, which are nanosized extracellular vesicles, play a critical role in mediating intercellular communication. More specifically, microRNA carried by exosomes are involved in various key processes such as nerve and vascular regeneration, and exosomes originating from Schwann cells, macrophages, and mesenchymal stem cells can promote peripheral nerve regeneration. In this review, the current knowledge of exosomes’ and their miRNA cargo’s role in peripheral nerve regeneration are summarized. The possible future roles of exosomes in therapy and the potential for microRNA-containing exosomes to treat peripheral nerve injuries are also discussed.

Background and Aim: Increasing evidence suggests that spinal cord injury (SCI)-induced defects in autophagic flux may contribute to an impaired ability for neurological repair following injury. Transcription factor E3 (TFE3) plays a crucial role in oxidative metabolism, lysosomal homeostasis, and autophagy induction. Here, we investigated the role of TFE3 in modulating autophagy following SCI and explored its impact on neurological recovery.