bioRxiv Science⌕ Search

bioRxiv · 10.1101/2023.07.28.550938

Clinical prediction of wound re-epithelisation outcomes in non-severe burn injury using the plasma lipidome

Abstract

Whilst wound repair in severe burns has received substantial research attention, non-severe burns (<20% total body surface area) remain relatively understudied, despite causing considerable physiological impact and constituting most of the hospital admissions for burns. Early prediction of healing outcomes would decrease financial and patient burden, and aid in preventing long-term complications from poor wound healing. Lipids have been implicated in inflammation and tissue repair and may play essential roles in burn wound healing. In this study, plasma samples were collected from 20 non-severe burn patients over 6 weeks from admission, including surgery, and analysed by liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy to detect 850 lipids and 112 lipoproteins. Orthogonal projections to latent structures-discriminant analysis was performed to identify changes associated with re-epithelialisation and delayed re-epithelisation. We demonstrated that the lipid and lipoprotein profiles at admission could predict re-epithelisation outcomes at 2 weeks post-surgery, and that these discriminatory profiles were maintained up to 6 weeks post-burn. Inflammatory markers GlycB and C-reactive protein indicated divergent systemic responses to the burn injury at admission. Triacylglycerols, diacylglycerols and low-density lipoprotein subfractions were associated with delayed wound closure (p-value <0.02, Cliffs delta >0.7), whilst high-density lipoprotein subfractions, phosphatidylinositols, phosphatidylcholines, and phosphatidylserines were associated with re-epithelisation at 2 weeks post-surgery (p-value <0.01, Cliffs delta <-0.7). Further model validation will potentially lead to personalised intervention strategies to reduce the risk of chronic complications post-burn injury.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ryan, M. J., Raby, E., Masuda, R., Lodge, S., Nitschke, P., Maker, G. L., Wist, J., Fear, M. W., Holmes, E., Nicholson, J., Gray, N., Whiley, L., Wood, F. M.. 2023-07-30. Clinical prediction of wound re-epithelisation outcomes in non-severe burn injury using the plasma lipidome. https://doi.org/10.1101/2023.07.28.550938

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

KEEP EXPLORING

Related preprints

Limit-pushing overexpression reveals constraints on protein abundance

Proteins are often classified as toxic or non-toxic without measuring the abundance reached, leaving constraints on tolerable protein abundance unresolved. We established a limit-pushing approach in Saccharomyces cerevisiae combining strong inducible expression with gTOW-mediated high-copy selection to counteract copy-number compensation while measuring protein abundance and growth. Nearly all of approximately 80 chromosome I proteins severely inhibited growth or reduced viability at sufficiently high abundance. We established IE50, the expression level associated with a 50% reduction in growth rate, to quantify their widely varying overexpression tolerance. IE50 was positively associated with predicted structural order and cytoplasmic localization propensity and negatively associated with sulphur content. Single-cell imaging linked higher tolerance to proteins remaining cytoplasmic without becoming aggregation-positive and revealed abundance-dependent changes in localization and organelle morphology. At extreme abundance, Fun12, Nup60, and Pex22 generated distinct large-scale intracellular states through specific sequence regions. These findings establish overexpression toxicity as a quantitative property linked to protein characteristics and reveal both constraints on tolerable abundance and sequence-dependent capacities for intracellular organization.

systems biology↗

Accessing Enzyme Kinetic Data and Prediction Methods at Scale

Enzyme kinetic parameters inform metabolic models, yet experimental measurements are sparse. A growing body of work predicts them from protein and substrate features, but software fragmentation hinders adoption, so downstream tools lock into the most accessible method. We present OpenKinetics Predictor (at predictor.openkinetics.org), an open-source platform integrating thirteen methods in isolated environments behind one interface. The platform optionally reports similarity between query proteins and each method's training data to contextualise reliability. A common featurisation-prediction abstraction keeps it extensible, and independent parties, including original authors, contributed many methods. We pair it with a data portal (at data.openkinetics.org) that exposes CatLog, a curated kinetic dataset, with precomputed embeddings, predicted binding sites, and standardised splits. Both offer a web interface and an API, and the GECKO modelling toolbox already calls the predictor API. As a case study, we predict across an E. coli model and find inter-predictor agreement varies with metabolic context and data availability.

systems biology↗

A thermoregulatory design principle for transitions into hypometabolism

Mammals entering torpor or hibernation undergo an abrupt transition from normothermia to hypothermia, yet how thermoregulation enables this switch remains poorly understood. Here, we identify dynamical signatures that precede these transitions and a mathematical principle that can generate them. In fasting-induced torpor in mice, body-temperature fluctuations increased before torpor onset, providing an early-warning signal that tracked proximity to the transition better than temperature decline alone. A heat-balance model showed that reducing how strongly the effective heat-loss coefficient depends on body temperature reorganizes thermoregulatory stability, allowing a low-temperature equilibrium to emerge while the normothermic state remains stable. This organization is consistent with a symmetry-broken pitchfork involving a saddle-node. Similar increases in temperature fluctuations preceded hibernation onset in hamsters. These findings link pre-transition temperature dynamics to changes in the underlying thermoregulatory landscape and provide a framework for detecting and understanding transitions from normothermia to hypothermia.

systems biology↗