Diabetic foot ulcer (DFU), characterized by high recurrence rate, amputations and mortality, poses a significant challenge in diabetes management. The complex pathology involves dysregulated glucose homeostasis leading to systemic and local microenvironmental complications, including peripheral neuropathy, micro- and macro-angiopathy, recurrent infection, persistent inflammation and dysregulated re-epithelialization. Novel approaches to accelerate DFU healing are actively pursued, with a focus on utilizing exosomes. Exosomes are natural nanovesicles mediating cellular communication and containing diverse functional molecular cargos, including DNA, mRNA, microRNA (miRNA), lncRNA, proteins, lipids and metabolites. While some exosomes show promise in modulating cellular function and promoting ulcer healing, their efficacy is limited by low yield, impurities, low loading content and inadequate targeting. Engineering exosomes to enhance their curative activity represents a potentially more efficient approach for DFUs. This could facilitate focused repair and regeneration of nerves, blood vessels and soft tissue after ulcer development. This review provides an overview of DFU pathogenesis, strategies for exosome engineering and the targeted therapeutic application of engineered exosomes in addressing critical pathological changes associated with DFUs.

Sepsis-associated encephalopathy (SAE) is a secondary cerebral dysfunction of the central nervous system (CNS) caused by sepsis and is associated with high mortality rate and poor prognosis. It significantly affects the quality of life of survivors. The pathological mechanisms associated with SAE include dysfunction of the blood–brain barrier (BBB), activation of glial cells, ischemic injury, leukocyte transmigration, and disturbances in neurotransmitters. The mechanisms of SAE interact with and contribute to its development. Numerous studies have demonstrated that the intestinal microbiota affects not only the health of the gut but also that of other organs. Throughout the progression of SAE, alterations in the gut microbiome composition lead to the production of toxic substances that damage the intestinal barrier and enter the bloodstream. This damage negatively affects BBB permeability and initiates a cascade of neuroinflammatory responses that result in neuronal injury. Conversely, specific microbiome-derived derivatives play exhibit a neuroprotective role in regulating brain function. Therefore, gut–brain crosstalk may be a crucial factor in brain dysfunction. This paper reviews the relationship between the intestinal microbiota and SAE, aiming to explore the role of the intestinal microbiota in SAE and potential therapeutic targets.