bioRxiv Science⌕ Search

bioRxiv · 10.1101/2021.04.08.438952

Lipid mediator profile of burn wound healing: Acellular cod fish skin grafts promote the formation of EPA and DHA derived lipid mediators during the first seven days

Abstract

The use of acellular fish skin grafts (FSG) for the treatment of burn wounds is becoming more common due to its beneficial wound healing properties. In our previous study we demonstarted that FSG is a scaffold biomaterial that is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) conjugated to phosphatidylcholines. Here we investigated whether EPA and DHA derived lipid mediators are influenced during the healing of burn wounds treated with FSG. Deep partial and full thickness burn wounds (DPT and FT respectively) were created on Yorkshire pigs (n=4). DPT were treated with either FSG or fetal bovine dermis while FT were treated either with FSG or cadaver skin initially and followed by a split thickness skin graft. Punch biopsies were collected on days 7, 14, 21, 28 and 60 and analysed in respect of changes to approximately 45 derivatives of EPA, DHA, arachidonic acid (AA), and linoleic acid (LA) employing UPLC-MS/MS methodology. Several EPA and DHA derivatives, including 18-HEPE and 17-HDHA, were significantly higher on day 7 in the DPT when treated with FSG. A similar but non-significant trend was observed for the FT. In addition, prostaglandin F2 and its 15-keto derivative (AA pathway) as well as 13-HODE and 13-HOTrE (LA pathway) were significantly lower in the FSG treated FT. The results suggest that the use of FSG in burn wound treatment can alter the formation of EPA and DHA mono hydroxylated lipid mediators in comparison to other grafts of mammalian origin. The differences observed during the first seven days after treatment indicates that FSG affects the early stages of wound healing. HighlightsO_LIThis is the first study to investigate whether omega-3 rich biomaterial such as fish skin graft can affect the lipidome of burn wound healing C_LIO_LIThe study monitors the formation of lipid mediators during 60 days of burn wound healing C_LIO_LIThis is the first study to show an increase in the formation of mono-hydroxylated derivatives of EPA and DHA after seven days of treatment with fish skin graft C_LIO_LIThe study showed significantly decreased formation of lipid mediators involved in pain modulation in wounds treated with fish skin graft C_LI

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kotronoulas, A., Karvelsson, S. T., Heijink, M., Stone, R., Giera, M., Rolfsson, O.. 2021-04-09. Lipid mediator profile of burn wound healing: Acellular cod fish skin grafts promote the formation of EPA and DHA derived lipid mediators during the first seven days. https://doi.org/10.1101/2021.04.08.438952

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The structures of two intermediates en route to DNA repair within a (6-4) photolyase

Pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are mutagenic DNA lesions produced when UV light crosslinks two adjacent pyrimidine bases. These lesions must be repaired to maintain genome integrity, a function executed by the (6-4) photolyase enzymes. This repair chemistry is complex, involving the transfer of a hydroxyl group from one base to another, accompanied or followed by cleavage of an interbase bond. It remains unclear how the enzyme orchestrates this reaction. Typically, models invoke a stepwise process in which an oxetane intermediate is transiently populated, but despite over thirty years of investigation, such an intermediate has never been definitively observed. Conducting dose-controlled X-ray crystallography on the (6-4) photolyase from Vibrio cholerae, we observed the transformation of 6-4PP into an oxetane species. Furthermore, we identified a previously unanticipated hemi-cleaved intermediate. The progressive transformation of 6-4PP into oxetane, hemi-cleaved, and fully repaired species requires a reexamination of the existing models of DNA repair by (6-4) photolyases.

biochemistry↗

Endothelial protein C receptor is an entry receptor for Langya virus

Langya virus (LayV) was recently discovered in infected individuals with febrile illness and classified as a Parahenipavirus, a group of poorly understood pathogens. LayV is distantly related to Nipah henipavirus which causes recurring outbreaks with case fatality rates reaching up to 90%. No vaccines or therapeutics are approved for use in humans for any parahenipavirus or henipavirus despite their broad geographic distribution and pandemic potential. Here, we discovered that human endothelial protein C receptor (EPCR) is an entry receptor for LayV and that the tetrameric LayV attachment glycoprotein (G) binds EPCR avidly. We reveal the molecular basis of LayV G recognition of the EPCR receptor and provide a blueprint of the determinants of receptor ortholog usage. We found that human and shrew EPCR orthologs promote cell entry of LayV and of the closely related Mojiang pseudoviruses. These results along with the detection of several Parahenipaviruses in shrews set these pathogens apart from Henipaviruses, which use Pteropid fruit bats as reservoir hosts. Our data support future surveillance efforts, by enabling prediction of EPCR utilization among newly discovered Parahenipaviruses, and the development and evaluation of countermeasures targeting this emerging group of human pathogens.

biochemistry↗

RNA-targeted aminopyridine compounds provide a new antifungal strategy

While RNA is an emerging therapeutic target class, progress is limited by a shortage of well-defined targets in which ligand binding is coupled to measurable function. The group I intron, a self-splicing ribozyme essential in fungal mitochondria but absent from humans, offers both a tractable platform for exploring first principles of small molecule-RNA targeting and a selective antifungal target. We recalibrated an intron-splicing assay to approximate cellular conditions and performed an extensive, cryo-EM-guided structure-activity relationship campaign against the Candida albicans mtLSU intron. Ligands containing a flexible diamine outperformed conformationally constrained analogues, suggesting a general principle for engaging dynamic RNA surfaces and yielding lead aminopyridine 56 (IC 21.6 nM). Compound 56 synergizes with amphotericin B against C. albicans, suggesting a path for combination therapies. RT-qPCR confirmed direct target engagement in cells. This work establishes the fungal group I intron as a viable, mechanistically distinct antifungal target and a model platform for RNA-targeted discovery.

biochemistry↗