Burns & Trauma最新文献

Acute kidney injury (AKI), a common kidney disease in which renal function decreases rapidly due to various etiologic factors, is an important risk factor for chronic kidney disease (CKD). The pathogenesis of AKI leading to CKD is complex, and effective treatments are still lacking, which seriously affects the prognosis and quality of life of patients with kidney disease. Nanomedicine, a discipline at the intersection of medicine and nanotechnology, has emerged as a promising avenue for treating kidney diseases ranging from AKI to CKD. Increasing evidence has validated the therapeutic potential of nanomedicine in AKI; however, little attention has been paid to its effect on AKI for patients with CKD. In this review, we systematically emphasize the major pathophysiology of the AKI-to-CKD transition and summarize the treatment effects of nanomedicine on this transition. Furthermore, we discuss the key role of nanomedicine in the regulation of targeted drug delivery, inflammation, oxidative stress, ferroptosis, and apoptosis during the transition from AKI to CKD. Additionally, this review demonstrates that the integration of nanomedicine into nephrology offers unprecedented precision and efficacy in the management of conditions ranging from AKI to CKD, including the design and preparation of multifunctional nanocarriers to overcome biological barriers and deliver therapeutics specifically to renal cells. In summary, nanomedicine holds significant potential for revolutionizing the management of AKI-to-CKD transition, thereby providing a promising opportunity for the future treatment of kidney diseases.

Background: Our previous research suggested that dexmedetomidine (Dex) promotes autophagy in cardiomyocytes, thus safeguarding them against apoptosis during sepsis. However, the underlying mechanisms of Dex-regulated autophagy have remained elusive. This study aimed to explore the role of exosomes and how they participate in Dex-induced cardioprotection in sepsis. The underlying microRNA (miRNA) mechanisms and possible therapeutic targets for septic myocardial injury were identified.

Methods: We first collected plasma exosomes from rats with sepsis induced by caecal ligation and puncture (CLP) with or without Dex treatment, and then incubated them with H9c2 cells to observe the effect on cardiomyocytes. Subsequently, the differential expression of miRNAs in plasma exosomes from each group of rats was identified through miRNA sequencing. miR-29b-3p expression in circulating exosomes of septic or non-septic patients, as well as in lipopolysaccharide-induced macrophages after Dex treatment, was analysed by quantitative real-time polymerase chain reaction (qRT-PCR). The autophagy level of cardiomyocytes after macrophage-derived exosome treatment was assessed by an exosome tracing assay, western blotting, and an autophagic flux assay. Specific miRNA mimics and inhibitors or small interfering RNAs were used to predict and evaluate the function of candidate miRNA and its target genes by qRT-PCR, annexin V/propyl iodide staining, autophagy flux analysis, and western blotting.

Results: We found that plasma-derived exosomes from Dex-treated rats promoted cardiomyocyte autophagy and exerted antiapoptotic effects. Additionally, they exhibited a high expression of miRNA, including miR-29b-3p. Conversely, a significant decrease in miR-29b-3p was observed in circulating exosomes from CLP rats, as well as in plasma exosomes from sepsis patients. Furthermore, Dex upregulated the lipopolysaccharide-induced decrease in miR-29b-3p expression in macrophage-derived exosomes. Exosomal miR-29b-3p from macrophages is thought to be transferred to cardiomyocytes, thus leading to the promotion of autophagy in cardiomyocytes. Database predictions, luciferase reporter assays, and small interfering RNA intervention confirmed that glycogen synthase kinase 3β (GSK-3β) is a target of miR-29b-3p. miR-29b-3p promotes cardiomyocyte autophagy by inhibiting GSK-3β expression and activation.

Conclusions: These findings demonstrate that Dex attenuates sepsis-associated myocardial injury by modulating exosome-mediated macrophage-cardiomyocyte crosstalk and that the miR-29b-3p/GSK-3β signaling pathway represents a hopeful target for the treatment of septic myocardial injury.