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In mammals, the cytokine hormone leptin promotes wound healing by increasing inflammation, cellular recruitment, angiogenic regrowth, and re-epithelialization; however, it is not known whether leptin has conserved actions on wound healing in other vertebrates. Here, we tested the hypothesis that leptin promotes both the quality and speed of wound healing in the South African clawed frog, Xenopus laevis . First, fluorescent immunohistochemistry using a polyclonal antibody specific to Xenopus leptin showed that in juvenile dorsal skin, leptin protein is expressed in the dorsal epidermal layer, as well in blood vessel endothelial cells and sensory nerves that run along the base of the dermis. Injection of recombinant Xenopus leptin (rXleptin) stimulates phosphorylated STAT3 (pSTAT3), indicative of leptin-activated JAK/STAT signaling in the epidermis. Similar to mammals, leptin protein expression increases at the wound site after injury of the epidermis. We then cultured “punch-in-a-punch” full-thickness dorsal skin explants in three doses of rXleptin (0, 10, and 100 ng/ml) and showed that leptin treatment doubled the rate of wound closure after 48 h relative to skin punches cultured without leptin. Food restriction prior to wound explant culture reduced the amount of wound closure, but leptin injection prior to euthanasia rescued closure to similar control levels. Leptin treatment also significantly reduced bacterial infection of these epidermal punches by 48 h in culture. This study shows that leptin is likely an endogenous promoter of wound healing in amphibians. Leptin-based therapies have the potential to expedite healing and reduce the incidence of secondary infections without toxicity issues, the threat of antibiotic resistance, or environmental antibiotic contamination. The conservation of leptin’s actions on wound healing also suggests that it may have similar veterinary applications for other exotic species.
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Harnessing Plasma Technology in Cream Formulations for Medical Applications as a Nitric Oxide Donor: Proof-of-Concept
Plasma's role in healthcare has been steadily gaining recognition, particularly for its capacity to produce reactive species that foster wound healing, combat microbial infections, and augment drug delivery. Despite its promise, implementation of plasma technologies is often impeded by logistical constraints, accessibility issues, and challenges integrating with established medical treatments. In this paper, we describe an innovative solution to deliver the benefits of plasma in healthcare: plasma-activated cream (PAC). PAC offers a versatile lipid-based platform for medical applications that transcends the traditional boundaries of plasma application by its flexible integration into a variety of treatment forms: as a cream base for transdermal applications, oil base for injectables, or incorporation with other biologics and lipid-soluble compounds. In this study, we reveal the novel method of creating PAC by infusing a lipophilic base with plasma-activated species, specifically focusing on nitric oxide (NO) and its related compounds (NOx). By measuring NOx concentrations before and after plasma treatment, we successfully validated the use of gliding-arc plasma to synthesize PAC. The NOx concentration rose from a baseline of 0 mg/L to an average of 2.0 mg/L post-treatment, indicative of successful infusion of plasma-activated species into PAC. This preliminary experiment unveils a novel pathway for incorporating plasma's beneficial effects into a lipid-based cream and shows the potential for PAC to act as NO storage. PAC not only brings forth new possibilities in wound-healing and antimicrobial treatments but also lays the groundwork for further exploration of plasma's role in enhancing drug delivery and NO storage.
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- Award ID(s):
- 1747671
- PAR ID:
- 10492864
- Publisher / Repository:
- BEGELL HOUSE Inc.
- Date Published:
- Journal Name:
- Plasma Medicine
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 1947-5764
- Page Range / eLocation ID:
- 65 to 71
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1615/PlasmaMed.2023049741
