Potentiating cutaneous wound healing in young and aged skin with nutraceutical collagen peptides.

BACKGROUND: Chronic wounds continue to be a burden to healthcare systems, with ageing linked to increased prevalence of chronic wound development. Nutraceutical collagen peptides have been shown to reduce signs of skin ageing, but their therapeutic potential for cutaneous wound healing remains undefined. AIM: To determine the potential for nutraceutical collagen peptides to promote cutaneous wound healing in vitro in the context of age. METHODS: The potential for bovine- or porcine-derived nutraceutical collagen peptides to promote wound healing of primary cutaneous fibroblasts and keratinocytes derived from young and aged individuals in vitro was assessed by two-dimensional scratch and cell-viability assays and by immunofluorescence for the cell proliferation marker, Ki67. The achievement of peptide concentrations in vivo, equivalent to those exerting a beneficial effect on wound healing in vitro, was confirmed by pharmacokinetic studies of hydroxyproline, a biomarker for collagen peptide absorption, following peptide ingestion by healthy individuals over a wide age range. RESULTS: Results demonstrated significant nutraceutical collagen peptide-induced wound closure of both young and aged fibroblasts and keratinocytes, mediated by enhanced cellular proliferation and migration. Analysis of blood levels of hydroxyproline in young and aged individuals following porcine collagen peptide ingestion revealed peak serum/plasma levels after 2 h at similar concentrations to those exerting beneficial effects on wound healing in vitro. CONCLUSION: These data demonstrate the capacity for nutraceutical collagen peptides to promote cutaneous wound closure in vitro, at pharmacologically achievable concentrations in vivo, thereby offering a potential novel therapeutic strategy for the management of cutaneous wounds in young and aged individuals.

Epidermal autophagy and beclin 1 regulator 1 and loricrin: a paradigm shift in the prognostication and stratification of the American Joint Committee on Cancer stage I melanomas.

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high-risk stage I tumour subsets. OBJECTIVES: To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma. METHODS: Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas. RESULTS: Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7-year disease-free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi-quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low-risk group (n = 239) vs. 85·4% in the AMLo high-risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69-9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93-9·56; P = 0·068) in stage IB patients. CONCLUSIONS: Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high-risk tumour subsets independently of Breslow depth. What's already known about this topic? There is an unmet clinical need for biomarkers of early-stage melanoma. Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor. Loricrin is a marker of epidermal terminal differentiation. What does this study add? AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation. The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth. What is the translational message? The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow-up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs.

Expression of Wnt genes in early wound healing.

The Wnt family of developmental genes has previously been shown to be involved in proliferation, differentiation, and cell to cell signaling during embryogenesis. In addition, several Wnt genes have been shown to be expressed during carcinogenesis. We have investigated these genes during the wound-healing process. Wnt-4 gene expression is found in mouse wounds from 2 hours to 30 hours postwounding. The expression of Wnt-4 is also stimulated by direct trauma to murine fibroblasts in culture, and the expression is greatly enhanced by the addition of a short plasmin digest of fibrin. Therefore the regulation of Wnt-4, appears to be complex, with expression being stimulated both by direct trauma and by the influence of clotting and fibrinolysis products. We propose that the expression of Wnt-4 in the early wound, in response to the provisional fibrin matrix, regulates cell movement and proliferation in the creation of new tissue by mechanisms related to those of embryogenesis.

Antigenic comparison of a truncated form of VP2 of infectious pancreatic necrosis (IPN) virus expressed in four different cell types.

A truncated form of the structural protein VP2 (truncVP2) of infectious pancreatic necrosis (IPN) virus encompassing amino acids 147-307 was expressed in bacterial, yeast, piscine and mammalian cells. All four recombinant antigens were recognised by a VP2-specific monoclonal antibody by ELISA and immunoblot analysis. However, the minimum amount of r-truncVP2 needed for detection by these methods varies depending on the cell type used for expression. Furthermore, all four recombinant preparations, when used to immunise Atlantic salmon, were capable of inducing antibodies reactive with whole IPNV in ELISA.