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

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

PROVIDER: PRJNA837872 | ENA |

REPOSITORIES: ENA

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

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.

2022-05-14 | GSE202952 | GEO

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

2022-05-12 | GSE202794 | GEO

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

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

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

| PRJNA837880 | 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

Smad7-based biologic targeting epidermis and stroma promotes healing of diabetic wounds in mice and pigs

Project description:Impaired healing of diabetic wounds causes significant morbidity and mortality. This study aimed to identify novel mechanisms of diabetic wound healing defects and test a therapeutic intervention using diabetic mouse and pig models. We found Smad7 transgene expression in mouse epidermis promoting wound healing in diabetic db/db mice, with reductions in obesity and blood glucose. To isolate effects of Smad7 on wounds, we created a Smad7-based biologic (Tat-PYC-Smad7) that penetrates wound cells. Topical application of Tat-PYC-Smad7 to diabetic pig and mouse wounds accelerated healing compared to controls. RNAseq analysis of mouse wound samples showed reduced TGFβ/NFκB signaling, leading to faster re-epithelialization and better extracellular matrix remodeling. Tat-PYC-Smad7 also attenuated neutrophil degranulation and NETosis by blocking histone 3 citrullination and inhibiting myeloperoxidase activities. Our study reveals that Tat-PYC-Smad7 promotes diabetic wound healing by targeting keratinocytes and neutrophils, providing insight into cellular mechanisms of diabetic wound healing defects targetable by Smad7-based therapy.

2024-08-13 | GSE274513 | 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

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

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

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