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ABSTRACT: Healing Outcomes of a Bio-Electric Wound Dressing for Post-Deroofing Care in Hidradenitis Suppurativa: A Split-Body, Randomized Clinical Trial

PROVIDER: PRJNA1055075 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27313816_1.fastq.gz	Fastqsanger.gz
	SRR27313816_2.fastq.gz	Fastqsanger.gz
	SRR27313817_1.fastq.gz	Fastqsanger.gz
	SRR27313817_2.fastq.gz	Fastqsanger.gz
	SRR27313818_1.fastq.gz	Fastqsanger.gz

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Therapeutic TNF Inhibitors Exhibit Differential Levels of Efficacy in Accelerating Cutaneous Wound Healing

Project description:Adalimumab is the only FDA- and EMA-approved treatment for moderate-to-severe hidradenitis suppurativa (HS), suggesting that the mechanism of action of adalimumab is distinct in HS and may contribute to improved wound healing. We have demonstrated that adalimumab, but neither etanercept nor certolizumab-pegol, induces a wound healing profile in vitro, which may underlie the differences in efficacy between various anti-TNF agents. To examine and compare the efficacy of therapeutic TNF inhibitors in chronic cutaneous wound healing in vivo, a human TNF knock-in Leprdb/db mouse model was established. The vehicle group exhibited severe impairments in cutaneous wound healing. In contrast, adalimumab significantly accelerated healing, confirmed by both histologic assessment and a unique healing transcriptional profile. Moreover, adalimumab and infliximab showed similar levels of efficacy, but golimumab was less effective, along with etanercept and certolizumab-pegol. In line with histologic assessments, proteomics analyses from healing wounds exposed to various TNF inhibitors revealed distinct and differential wound healing signatures that may underlie the differential efficacy of therapeutic inhibitors in accelerating chronic wound healing.

2023-09-11 | PXD040275 | Pride

Therapeutic TNF Inhibitors Exhibit Differential Levels of Efficacy in Accelerating Cutaneous Wound Healing

Project description:Adalimumab, but neither etanercept nor certolizumab-pegol, has been reported to induce a wound healing profile in the circulation of patients with hidradenitis suppurativa (HS), a chronic inflammatory skin disease. However, the role of tumor necrosis factor alpha (TNF) inhibitors in cutaneous wound healing in vivo is still unclear. To examine and compare the efficacy of various TNF inhibitors in cutaneous wound healing in vivo, a human TNF knock-in Leprdb/db mouse model was established to model the impaired cutaneous wound healing as seen in HS. The vehicle group exhibited severe impairments in cutaneous wound healing. In contrast, adalimumab significantly accelerated healing, confirmed by both histologic assessment and a unique healing transcriptional profile. Moreover, adalimumab and infliximab showed similar levels of efficacy, but golimumab was less effective, along with etanercept and certolizumab-pegol. In line with histologic assessments, proteomics analyses from healing wounds exposed to various TNF inhibitors revealed distinct and differential wound healing signatures that may underlie the differential efficacy of these inhibitors in accelerating cutaneous wound healing. Taken together, these data revealed that TNF inhibitors exhibited differential levels of efficacy in accelerating cutaneous wound healing in the impaired wound healing model in vivo likely through distinct mechanisms of action related to the structure of the biologic or its ability to bind TNF.

2023-09-11 | GSE242837 | GEO

Single cell RNA-seq analyses of dermis from wound day 18 large skin wounds that healed in a fibrotic or regenerative fashion.

Project description:Human and murine skin wounding commonly result in fibrotic scarring but the murine wounding model Wound Induced Hair Neogenesis (WIHN) can frequently result in a regenerative repair response. Here we show in single cell RNA-seq comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity. In accordance, phagocytosis abrogation resulted in transient Wnt activity and a more regenerative healing. Phagocytosis of SFRP4 was integrin-mediated and dependent on the interaction of SFRP4 with the EDA splice variant of fibronectin. In the human skin condition Hidradenitis suppurativa, phagocytosis of SFRP4 by macrophages correlated with fibrotic wound repair. These results reveal that macrophages can modulate a key signaling pathway via phagocytosis to alter the skin wound healing fate.

2019-12-12 | GSE141814 | GEO

RNA sequencing of skin punch biopsies of lesional and non-lesional skin from hidradenitis suppurativa patients

Project description:This study investigated the underlying inflammatory pathways and cell types in hidradenitis suppurativa using transcriptomic approaches with RNA sequencing of lesional and non-lesional skin biopsies from hidradenitis suppurativa patients.

2023-12-06 | GSE249027 | GEO

Adalimumab Induces a Wound Healing Profile in Patients with Hidradenitis Suppurativa by Regulating Macrophage Differentiation and Matrix Metalloproteinase Expression

Project description:Adalimumab (ADA) is the only FDA-approved treatment for moderate-to-severe hidradenitis suppurativa (HS), whereas etanercept (ETN) and certolizumab-pegol (CZP) have been shown to be ineffective, suggesting that the mechanism of action of ADA is distinct in HS and may contribute to improved wound healing. Given that macrophages (Mφ) play pivotal roles throughout the wound healing process, an in-vitro Mφ differentiation assay was carried out to assess the impact of TNF-anti-TNF complexes on these cells. TNF-ADA complexes exhibited stronger inhibitory effects on inflammatory Mφ differentiation. Moreover, RNA sequencing revealed several unique wound healing profiles for TNF-ADA-treated inflammatory Mφs, which were not observed for those treated with either TNF-ETN or TNF-CZP, including the inhibition of the matrix metallopeptidase (MMP) pathway. In addition, ADA administration was found to significantly reduce the levels of inflammatory MMPs -1 and -9 while promoting wound healing MMP-13 and tissue inhibitor of metalloproteinases 2 (TIMP-2) levels in the circulation of those HS patients who responded to treatment. Our in-vitro findings demonstrate that TNF-ADA-treated inflammatory Mφs exhibit a distinct profile resembling wound healing. Moreover, ADA not only differentially regulates MMP expression in HS patients responding to the therapy but potentially induces a transition to a profile suggestive of wound healing.

2021-04-14 | GSE166920 | GEO

Alterations to the Hidradenitis Suppurativa Serum Proteome with Spleen Tyrosine Kinase Antagonism: Proteomic Results from a Phase 2 Clinical Trial.

Project description:Serum Proteomic Analysis of patients with Hidradenitis Suppurativa treated with Fostamatinib

2023-08-10 | GSE240607 | GEO

Gene expression profiling of blood in hidradenitis suppurativa

Project description:To acquire a better understanding of the molecular pathogenesis of hidradenitis suppurativa (HS), we performed mRNA microarray studies to compare whole blood gene expression of HS patients to that of healthy normal subjects. No significant difference was observed in whole blood mRNA expression between HS patients and healthy normal control. Whole blood samples were collected from patients with hidradenitis (n=16) at baseline and healthy normal subjects (n=10) for RNA extraction and microarray analysis.

2016-03-11 | E-GEOD-79149 | biostudies-arrayexpress

Effect of Electrospun Poly (L-lactide-co-caprolactone) and Formulated Porcine Fibrinogen for Diabetic Foot Ulcers

Project description:OBJECTIVE To compare the effect of topical application PLCL/Fg dressing with alginate dressing (ConvaTec Ltd) when treating DFUs. DESIGN, SETTING, AND PARTICIPANTS A single-center, prospective, randomized, patient-blinded clinical trial was conducted from February 1, 2023, to November 16, 2023. The eligible patients with DFUs of 1 to 20 cm2 present for at least 1 month and with Wagner grade 1 or 2. They were randomized 1:1 to receive PLCL/Fg or control alginate dressing. In PLCL/Fg group, 10 wounds samples were got from five patients at the time of the first dressing application and 50% wound healing time point. The wound specimens were subjected to messenger RNA sequencing. INTERVENTIONS Participants received PLCL/Fg dressing 1 to 3 times per week or Alginate dressing 3 times per week for 12 weeks. MAIN OUTCOMES AND MEASURES Primary end point was the incidence of complete healing. Complete healing was defined as complete re-epithelialization of the ulcer bed and absence of secretion. Secondary end points were time to relevant 50% wound reduction, infection, treatment-associated adverse events, and the microenvironment changing during wound healing.

2024-12-26 | GSE269483 | GEO

A Hidradenitis Suppurativa Molecular Disease Signature Derived from Patient Samples by High-Throughput RNA Sequencing

Project description:Hidradenitis suppurativa is a common, debilitating inflammatory skin disease linked to immune dysregulation and abnormalities in follicular structure and function. Few studies have characterized the transcriptomic profile of affected and unaffected skin. We established an RNA-Seq based hidradenitis suppurativa expression disease signature and found it largely concordant with an earlier microarray-based study. We confirmed known aspects of the underlying disease biology including known immune response pathways, differential regulation of antimicrobial peptides, and complement activation. We further characterize the extent of changes in the complement cascade in hidradenitis lesions and highlight a signature that implicates host response to bacteria in disease pathogenesis.

2020-12-31 | GSE151243 | GEO

Rapid Attenuation of B-Cell and Interferon Gamma Associated Chemokines in Clinical Responders to Janus Kinase Inhibition with Upadacitinib in Hidradenitis Suppurativa.

Project description:Serum Proteomic Analysis of patients with Hidradenitis Suppurativa treated with 15mg daily of Upadacitinib. Samples from Week 0 and Week 4 of therapy, Straficied by clinical response.

2023-06-18 | GSE235140 | GEO

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