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A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers.

ABSTRACT: Cellular mechanisms and/or microbiological interactions which contribute to chronic diabetes related foot ulcers (DRFUs) were explored using serially collected tissue specimens from chronic DRFUs and control healthy foot skin. Total RNA was isolated for next-generation sequencing. We found differentially expressed genes (DEGs) and enriched hallmark gene ontology biological processes upregulated in chronic DRFUs which primarily functioned in the host immune response including: (i) Inflammatory response; (ii) TNF signalling via NFKB; (iii) IL6 JAK-STAT3 signalling; (iv) IL2 STAT5 signalling and (v) Reactive oxygen species. A temporal analysis identified RN7SL1 signal recognition protein and IGHG4 immunoglobulin protein coding genes as being the most upregulated genes after the onset of treatment. Testing relative temporal changes between healing and non-healing DRFUs identified progressive upregulation in healed wounds of CXCR5 and MS4A1 (CD20), both canonical markers of lymphocytes (follicular B cells/follicular T helper cells and B cells, respectively). Collectively, our RNA-seq data provides insights into chronic DRFU pathogenesis.

SUBMITTER: Radzieta M

PROVIDER: S-EPMC9320801 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers.

Radzieta Michael M Peters Timothy J TJ Dickson Hugh G HG Cowin Allison J AJ Lavery Lawrence A LA Schwarzer Saskia S Roberts Tara T Jensen Slade O SO Malone Matthew M

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 20220510 7

Cellular mechanisms and/or microbiological interactions which contribute to chronic diabetes related foot ulcers (DRFUs) were explored using serially collected tissue specimens from chronic DRFUs and control healthy foot skin. Total RNA was isolated for next-generation sequencing. We found differentially expressed genes (DEGs) and enriched hallmark gene ontology biological processes upregulated in chronic DRFUs which primarily functioned in the host immune response including: (i) Inflammatory re ...[more]

PMID: 35394091

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Project description:BackgroundDiabetes-related foot ulceration (DFU) has a substantial burden on both individuals and healthcare systems both globally and in Australia. There is a pressing need for updated guidelines on wound healing interventions to improve outcomes for people living with DFU. A national expert panel was convened to develop new Australian evidence-based guidelines on wound healing interventions for people with DFU by adapting suitable international guidelines to the Australian context.MethodsThe panel followed National Health and Medical Research Council (NHMRC) procedures to adapt suitable international guidelines by the International Working Group of the Diabetic Foot (IWGDF) to the Australian context. The panel systematically screened, assessed and judged all IWGDF wound healing recommendations using ADAPTE and GRADE frameworks for adapting guidelines to decide which recommendations should be adopted, adapted or excluded in the Australian context. Each recommendation had their wording, quality of evidence, and strength of recommendation re-evaluated, plus rationale, justifications and implementation considerations provided for the Australian context. This guideline underwent public consultation, further revision and approval by ten national peak bodies.ResultsThirteen IWGDF wound healing recommendations were evaluated in this process. After screening, nine recommendations were adopted and four were adapted after full assessment. Two recommendations had their strength of recommendations downgraded, one intervention was not currently approved for use in Australia, one intervention specified the need to obtain informed consent to be acceptable in Australia, and another was reworded to clarify best standard of care. Overall, five wound healing interventions have been recommended as having the evidence-based potential to improve wound healing in specific types of DFU when used in conjunction with other best standards of DFU care, including sucrose-octasulfate impregnated dressing, systemic hyperbaric oxygen therapy, negative pressure wound therapy, placental-derived products, and the autologous combined leucocyte, platelet and fibrin dressing. The six new guidelines and the full protocol can be found at: https://diabetesfeetaustralia.org/new-guidelines/ CONCLUSIONS: The IWGDF guideline for wound healing interventions has been adapted to suit the Australian context, and in particular for geographically remote and Aboriginal and Torres Strait Islander people. This new national wound healing guideline, endorsed by ten national peak bodies, also highlights important considerations for implementation, monitoring, and future research priorities in Australia.

Project description:BackgroundFor patients with diabetic foot ulcers, offloading is one crucial aspect of treatment and aims to redistribute pressure away from the ulcer site. In addition to offloading strategies, patients are often advised to reduce their activity levels. Consequently, patients may avoid exercise altogether. However, it has been suggested that exercise induces an increase in vasodilation and tissue blood flow, which may potentially facilitate ulcer healing. The aim of this systematic review was to determine whether exercise improves healing of diabetic foot ulcers.ReviewWe conducted a systematic search of MEDLINE, CINAHL and EMBASE between July 6, 2009 and July 6, 2019 using the key terms and subject headings diabetes, diabetic foot, physical activity, exercise, resistance training and wound healing. Randomised controlled trials were included in this review. Three randomised controlled trials (139 participants) were included in this systematic review. All studies incorporated a form of non-weight bearing exercise as the intervention over a 12-week period. One study conducted the intervention in a supervised setting, while two studies conducted the intervention in an unsupervised setting. Two studies found greater improvement in percentage wound size reduction in the intervention group compared with the control group, with one of these studies achieving statistically significant findings (p < 0.05). The results of the third study demonstrated statistically significant findings for total wound size reduction (p < 0.05), however results were analysed within each treatment group and not between groups.ConclusionThis systematic review found there is insufficient evidence to conclusively support non-weight bearing exercise as an intervention to improve healing of diabetic foot ulcers. Regardless, the results demonstrate some degree of wound size reduction and there were no negative consequences of the intervention for the participants. Given the potential benefits of exercise on patient health and wellbeing, non-weight bearing exercise should be encouraged as part of the management plan for treatment of diabetic foot ulcers. Further research is required to better understand the relationship between exercise and healing of diabetic foot ulcers.

Dataset Information

A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers.

Publications

A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers.

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