Koo S, et al. Nutr Res Pract. 2021 Apr;15(2):160-172. https://doi.org/10.4162/nrp.2021.15.2.160

Messenger RNA (mRNA) vaccines have exhibited promising potential for infectious disease prevention. Although various delivery methods have been explored, the use of electroporation (EP) for the delivery of naked mRNA has received relatively less attention. In this study, we used mouse models to investigate whether naked mRNA vaccine delivery via intramuscular EP (IM-EP) elicits a protective immune response against lethal viral infection. To achieve this, we injected C57BL/6 mice with naked mRNA encoding the SARS-CoV-2 mRNA vaccine via IM-EP and evaluated the resulting immune responses. IM-EP-mediated delivery of the mRNA vaccine induced robust humoral and cellular immune responses, characterized by elevated SARS-CoV-2 receptor-binding domain (RBD)-specific IgG antibodies, enhanced IFN-γ production by CD8⁺ T cells, and upregulated cytokine expression in the muscle and lymph nodes. Using the K18-hACE2 mouse model, we revealed that IM-EP-mediated delivery of the naked mRNA vaccine effectively protected mice from lethal SARS-CoV-2 infection. Overall, our findings suggest that the delivery of naked mRNA via IM-EP can be an effective strategy for preventing infectious diseases.

Cisplatin is an effective chemotherapeutic agent, yet its clinical utility is limited by dose-dependent nephrotoxicity. Alpha-1 antitrypsin (AAT) has cytoprotective, anti-inflammatory, and antiapoptotic properties, but its therapeutic potential in cisplatin-induced acute kidney injury (AKI) remains unclear. A murine cisplatin–AKI model was used to evaluate whether AAT (80 mg/kg) ameliorates renal injury. Renal function, oxidative stress, NADPH oxidase (NOX) isoforms, mitochondrial metabolism, inflammatory mediators, apoptosis, and fibrosis-related markers were assessed using biochemical, histological, immunohistochemical, and Western blot analyses. Cisplatin markedly impaired renal function and induced tubular injury; meanwhile, AAT significantly reversed these changes. Cisplatin also induced severe oxidative stress and disrupted the balance of NOX isoforms; AAT restored redox homeostasis. Cisplatin upregulated CPT1A/PDK4 and suppressed CPT2, UCP3, PGC1α, and DRP1, inducing maladaptive mitochondrial changes, indicating impaired β-oxidation and defective mitochondrial dynamics; AAT reversed these alterations, restoring normal mitochondrial metabolism. IL-1β, IL-6R, OPN, and F4/80 expression, recovery of the Bax/Bcl-2 ratio, and MAPK activation were reduced, indicating decreased inflammation and apoptosis; profibrotic markers were also reduced. AAT confers multifaceted protection against cisplatin-induced AKI by restoring redox balance, mitochondrial homeostasis, and inflammatory and apoptotic signaling. These findings support AAT as a promising therapeutic agent for preventing cisplatin nephrotoxicity.

Journal of Biomedical and Translational Research