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Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HDFa]

ABSTRACT: Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HDFa]

PROVIDER: PRJNA837880 | ENA |

REPOSITORIES: ENA

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Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HEKa]

Project description:The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is a significant clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here we report a novel class of epoxy-tiglianes and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens. In vitro, the lead candidate, EBC-1013 stimulated PKC-dependent neutrophil ROS induction and NETosis, and increased expression of wound healing associated cytokines, chemokines and antimicrobial peptides in keratinocytes and fibroblasts. In vivo, topical EBC-1013 induced rapid resolution of infection with increased matrix remodelling in acute thermal injuries. In chronically-infected, diabetic wounds, treatment induced cytokine/chemokine production, inflammatory cell recruitment and complete healing (in 6/7 wounds) with ordered keratinocyte differentiation. These results highlight a non-antibiotic approach involving contrasting, orthogonal mechanisms of action: targeted biofilm disruption and innate immune induction in the treatment of chronic wounds.

2022-05-12 | GSE202794 | GEO

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HDFa]

2022-05-14 | GSE202952 | GEO

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds

Project description:Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds

| PRJNA837872 | ENA

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HEKa]

Project description:Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HEKa]

| PRJNA837275 | ENA

Wound healing and hair follicle regeneration with topical BRAF inhibitor therapy in a diabetic model

Project description:Wound healing is a multi-step process to rapidly restore barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model, but unexpectedly promotes hair follicle regeneration. Neogenic hair follicles expressing Sox-9, CD34 and K15 were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.

2021-05-22 | GSE148037 | GEO

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-05-14 | GSE202953 | GEO

Circular RNA signatures of human healing and non-healing wounds

Project description:Circular RNA signatures of human healing and non-healing wounds

| PRJNA780818 | ENA

Pharmacological YAP activation promotes regenerative repair of cutaneous wounds.

Project description:Chronic cutaneous wounds remain a persistent unmet medical need that decrease expectancy and quality of life. Here, we report that topical application of PY-60, a small molecule activator of the transcriptional coactivator YAP, promotes regenerative repair of cutaneous wounds in pig and human models. Pharmacological YAP activation enacts a reversible pro-proliferative transcriptional program in keratinocytes and dermal cells that results in accelerated re-epithelization and regranulation of the wound bed. These results demonstrate that transient topical administration of a YAP activating agent may represent a generalizable therapeutic approach to treating chronic wounds.

2023-06-11 | GSE234332 | GEO

Transcription profiling by array of excisional biopsy wounds from young and old human subjects to measure the influence of age on cutaneous wound healing

Project description:The aim of this experiment was measure the influence of age on cutaneous wound healing using human subjects. Increaded age has been associated with delayed wound healing in mouse models and in humans. Gene expression was compared between excisional biopsy wounds from young and old subjects.

2008-04-10 | E-MEXP-1074 | biostudies-arrayexpress

Topical estrogen application promotes cutaneous wound healing in db/db female mice with type 2 diabetes

Project description:Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3–14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1–14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes.

2022-02-15 | GSE182906 | GEO

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