Debate regarding the co-existence of Staphylococcus aureus and Pseudomonas aeruginosa in wounds remains contentious, with the dominant hypothesis describing a situation akin to niche partitioning, whereby both microorganisms are present but occupy distinct regions of the wound without interacting. In contrast, we hypothesised that these microorganisms do interact during early co-colonisation in a manner beneficial to both bacteria. We assessed competitive interaction between S. aureus and P. aeruginosa in biofilm cultured for 24-72 h and bacterial aggregates analogous to those observed in early (<24 h) biofilm formation, and interaction with human keratinocytes. We observed that S. aureus predominated in biofilm and non-attached bacterial aggregates, acting as a pioneer for the attachment of P. aeruginosa. We report for the first time that S. aureus mediates a significant (P < 0.05) increase in the attachment of P. aeruginosa to human keratinocytes, and that P. aeruginosa promotes an invasive phenotype in S. aureus. We show that co-infected keratinocytes exhibit an intermediate inflammatory response concurrent with impaired wound closure that is in keeping with a sustained proinflammatory response which allows for persistent microbial colonisation. These studies demonstrate that, contrary to the dominant hypothesis, interactions between S. aureus and P. aeruginosa may be an important factor for both colonisation and pathogenicity in the chronic infected wound.

Vicenin-2, a C-glycoside flavone that is present in many plant sources, exerts potent antiinflammatory effects in a number of cell and animal models of inflammation. Ten-eleven translocation (TET)-2 has recently gained considerable attention due to the role it plays in regulating the inflammasome. We studied the ability of Vicenin-2 (V-2) to regulate a range This study demonstrates that the anti-inflammatory actions of V-2 are associated not only with increased IL-10 and IL-1Ra expression but also with TET-2 expression. Further work is required to establish if the effects of V-2 can be definitively linked to TET-2 activity and that these actions are mirrored in a range of relevant cell types.

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Chronic wounds, including pressure ulcers, foot ulcers and venous leg ulcers have a detrimental impact on the health and well-being of an estimated 2% of people in the UK.Chronic wounds are normally colonised by bacteria and in some instances bacterial load increases sufficiently for infection to ensue. Once a chronic wound becomes infected it is difficult to resolve and a combination of continuous inflammation and bacterial proliferation makes these wounds difficult to manage. A state of prolonged inflammation can occur as a result of impaired homeostatic pathways which are exacerbated by bacterial growth.Chronic, infected wounds can persist for many months or even years, sometimes requiring surgical intervention in the form of regular debridement or amputation when other strategies such as antimicrobial treatments fail. The complex relationships between both oral microbiota and the host have been extensively characterised, including the shift from health to disease, and has allowed for the development of numerous control strategies. This knowledge combined with contemporary studies of chronic infected wounds can be used to develop an understanding of the relationship between the host and microorganism in the chronic wound environment. Such information has the potential to inform wound management including strategies to control infection and promote wound healing.

Numerous natural compounds including Nigella sativa (N. sativa) demonstrate anti-inflammatory and anti-diabetic antiangiogenic properties. Lipopolysaccharide (LPS) mediated inflammation is regarded as an important contributor to the inflammation that is associated with the development of arteriosclerosis. In this study, it was hypothesised that N. sativa Extract (NSE) and its main active component Thymoquinone (TQ) could potentially inhibit LPS mediated inflammatory cytokine secretion and monocyte recruitment factors and monocyte in Human Vascular Endothelial Cell (HECV) lines. In addition the Ten-Eleven Translocation (TET-2) an epigenetic regulator, increasingly regarded has having a major role in both the regulation of cytokine secretion and in the development of atherosclerosis through its ability to inhibit the inflammasome Nod-like Receptor Protein 3 (NLRP3) and Interleukin-1b (IL-1b) secretion was investigated. NSE significantly inhibited the production of both IL-6 and-8 and both NSE and TQ inhibited the gene expression of vascular endothelial growth factor and monocyte chemotactic protein-1 in HECV cells. NSE and TQ inhibited the gene expression of NLRP3 and IL-1b and significantly upregulated the gene expression of TET-2 in the presence of LPS. To conclude, NSE and TQ attenuated inflammatory and monocyte recruitment response and also demonstrate a potentially important role in regulating both NLRP3 and TET-2 expression.

Background: Macrophages are key cellular mediators in diabetes-related inflammation. Molecular cues such as cytokines found in the tissue microenvironment regulates the polarization of macrophages into an M1 (pro-inflammatory) or M2 (immunoregulatory) phenotype. Recent evidence suggests that M1 macrophages in diabetic patients may contribute to the complications associated with the disease such as atherosclerosis. Trigonella foenum- graecum (Tfg: fenugreek) seeds have been used in traditional medicine in Asia, Africa and the Middle-East for their alleged anti-diabetic properties.Objective: To identify the molecular mechanism(s) through which Tfg seeds exert their effects, we investigated the role of a crude methanolic extract of Tfg (FME) seeds on macrophage polarization in vitro.Method: THP-1 macrophages (Mϕ) were treated with gBSA in the presence/absence of FME and the release and expression of M1 and M2 markers/cytokines were analysed. The role of FME on NF-κB activity was also explored using transfected HEK-293T cells.Results: This study found that the FME significantly (P<0.05) decreased gBSA-induced secretion of M1 cytokines (TNF-α, IL-1β, IL-6 and IL-8) in THP-1 Mϕ cells. In the presence of gBSA, FME also significantly increased the gene expression of the M2 marker Dectin-1, but had no effect on IL-10, IL-1Ra.  FME also significantly decreased TNF-α induced NF-kB reporter activity.Conclusion: These results suggest that FME can regulate the expression of M1 and M2 markers in THP-1 Mϕ cells. This may be potentially through the modulation of NF-kB activity. Further work should be carried out to identify precise mechanism(s) involved in the effects of FME and Tfg seeds.Keywords: chronic inflammation, macrophage polarization, diabetes, glycated BSA, THP-1 cells, Trigonella foenum graecum, fenugreek seeds, NF-κB,