Over the past 10 years, the crisis of sepsis has remained a great challenge. According to data from 2016, the sepsis-related mortality rate remains high. In addition, sepsis consumes extensive medical resources in intensive care units, and anti-inflammatory agents fail to improve sepsis-associated hyperinflammation and symptoms of immunosuppression. The specific immune mechanism of sepsis remains to be elucidated. Reactive oxygen species (ROS) are triggered by energy metabolism and respiratory dysfunction in sepsis, which not only cause oxidative damage to tissues and organelles, but also directly and indirectly promote NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. NLRP3 inflammasomes enlarge the inflammatory response and trigger apoptosis of immune cells to exacerbate sepsis progression. Inhibiting the negative effects of ROS and NLRP3 inflammasomes therefore provides the possibility of reversing the excessive inflammation during sepsis. In this review, we describe the interaction of ROS and NLRP3 inflammasomes during sepsis, provide prevention strategies, and identify fields that need further study.

Loss of periodontal tissue due to persistent inflammation in periodontitis is a major cause of tooth loss in adults. Overcoming osteogenic inhibition in the inflammatory periodontal environment and restoring the regenerative capacity of endogenous bone marrow mesenchymal stem cells (BMSCs) remain critical challenges in current treatment approaches. Macrophage‐derived extracellular vesicles (EVs) are key regulators of osteogenesis in recipient cells, yet the role of erythropoietin (EPO) in modifying macrophages and the function of their EVs in bone regeneration remain unclear. In this study, EVs from EPO‐stimulated macrophages (EPO‐EVs) are isolated, and they are encapsulated in a chitosan/β‐sodium glycerophosphate/gelatin (CS/β‐GP/gelatin) hydrogel to create a controlled‐release EVs delivery system for localized periodontal environment. EPO‐EVs restore the osteogenic function of mouse BMSCs (mBMSCs) and mitigate inflammatory bone loss in a periodontitis mouse model. Mechanistically, miR‐5107‐5p, significantly enriched in EPO‐EVs, is delivered to mBMSCs, where it suppresses epidermal growth factor receptor (EGFR) expression and alleviates EGFR's inhibitory effect on RhoA. This process counteracts osteogenic inhibition in inflammatory settings through the EGFR/RhoA axis. Overall, EVs from EPO pretreated macrophages restore the osteogenic capacity of mBMSCs under inflammation by inhibiting EGFR expression, providing new insight into therapeutic mechanisms and offering a promising approach for future periodontitis treatment.