Downregulation of S100a7a antimicrobial peptide in acne vulgaris patients after isotretinoin therapy

Al‐Sudany, Nameer K.; Mohammed, Nadia H.; Alrifai, S. B.

doi:10.1111/dth.13136

Cited by 8 publications

(8 citation statements)

References 20 publications

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“…S100A7A encodes an antimicrobial peptide that has been identified as a potential drug target in patients diagnosed with acne vulgaris. 58 Finally, our findings revealed that TCF23 was expressed primarily in the peri-wounds subregion. TCF23 encodes a progesteroneinduced transcription factor required for decidualization of human endometrial stromal cells.…”

Section: Discussionmentioning

confidence: 55%

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Molecular characterization of chronic cutaneous wounds reveals subregion‐ and wound type‐specific differential gene expression

Richards,

Gubser Keller,

Kreutzer

et al. 2023

International Wound Journal

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A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri‐wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA‐Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine‐like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.

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Section: Discussionmentioning

confidence: 55%

“…We further postulated that elevated levels of S100A7A identify wound border subregions. S100A7A encodes an antimicrobial peptide that has been identified as a potential drug target in patients diagnosed with acne vulgaris 58 . Finally, our findings revealed that TCF23 was expressed primarily in the peri‐wounds subregion.…”

Section: Discussionmentioning

confidence: 63%

Molecular characterization of chronic cutaneous wounds reveals subregion‐ and wound type‐specific differential gene expression

Richards,

Gubser Keller,

Kreutzer

et al. 2023

International Wound Journal

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“…Among 2461 potential studies, 206 satisfied the inclusion criteria (eFigure in the Supplement). Among included trials, 163 (79%) were for acne and 43 (21%) were for rosacea. Rosacea RCTs were more likely to include at least 1 PROM (67% [n = 29 of 43]) compared with acne RCTs…”

Section: Resultsmentioning

confidence: 99%

Use of Patient-Reported Outcomes in Acne Vulgaris and Rosacea Clinical Trials From 2011 to 2021

Miller

Tong

et al. 2022

JAMA Dermatol

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ImportanceAcne and rosacea have substantial implications for quality of life, and it is therefore important to ensure the patient’s voice is being captured in pivotal randomized clinical trials (RCTs). Although patient-reported outcome measures (PROMs) are a valuable tool to capture the patient perspective, little is known about use of PROMs in RCTs on acne and rosacea.ObjectiveTo characterize the use of PROMs in RCTs on acne and rosacea.Evidence ReviewA systematic literature search was conducted using the search terms acne vulgaris and rosacea in the following databases: MEDLINE through PubMed, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. A modified search hedge for RCTs from the McGill Library was applied. All phase 2, 3, and 4 RCTs published between December 31, 2011, through December 31, 2021, that evaluated the efficacy and safety of therapies for acne and rosacea vs any comparator were eligible for inclusion.FindingsA total of 2461 publications describing RCTs were identified, of which 206 RCTs met the inclusion criteria (163 trials [79%] on acne and 43 [21%] on rosacea). At least 1 PROM was used in 53% of trials (110) included; PROM use was more common in rosacea RCTs (67% [n = 29]) compared with acne RCTs (50% [n = 81]). At least 1 dermatology-specific (13% [n = 27]) or disease-specific (14% [n = 28]) PROM was included in the RCTs analyzed. Only 7% of trials (14) included a PROM as a primary outcome measure. There was no statistically significant increase in PROM inclusion over the study period (11 of 21 trials in 2011 vs 5 of 12 trials in 2021).Conclusions and RelevanceIn this systematic review, PROMs were included in approximately one-half of acne and rosacea RCTs performed over the study period. In addition, PROMs were rarely used as a primary outcome measure, and inclusion of PROMs has not increased substantially over the past 10 years. Increasing use of PROMs in RCTs can ensure that the patient’s perspective is captured during the development of new treatments for acne and rosacea.

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“…Isotretinoin makes this effect through suppression of mTORC1 and downregulation of inflammatory driving protein, S100a7a. [16,17] Limitations: This was a single-center retrospective study and the results may not be generalizable to other populations. The historical laboratory data was extracted from our hospital management system, not a controlled trial.…”

Section: Discussionmentioning

confidence: 96%

Sistemik İsotretinoin Tedavisi Alan Akne Vulgaris Hastalarında Nötrofil- Lenfosit Oranı ve C-Reaktif Protein Düzeyleri

Yavuz¹

2021

Journal of Contemporary Medicine

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Introduction: Inflammatory mediators have importance in acne vulgaris pathogenesis. Which mediators cause lesions or increase with which variants is not clear. Neutrophil-lymphocyte ratio and C-reactive protein are the inflammatory indicators that used for follow up of inflammatory diseases. There are various studies state that neutrophil-lymphocyte ratio and C-reactive protein levels are important for systemic isotretinoin treatment or not. Evaluation of changes in neutrophil-lymphocyte ratio and C-reactive protein levels with systemic isotretinoin treatment is the aim of this study. Material andMethod: Acne vulgaris patients who are treated with systemic isotretinoin and healthy control subjects between January 2006 and December 2016 in Konya Training and Research Hospital Dermatology outpatient clinic are included to study. Neutrophillymphocyte ratio and C-reactive protein levels compared in each group at the beginning of treatment and at the 3rd month.Results: 50 patients (28 of women and 22 of men) who are treated with systemic isotretinoin for acne vulgaris and 50 healthy control patients (21 of women and 29 of men) included to study. Mean age of treatment group was 21 (19-23) and control group was 29,5. Neutrophil-lymphocyte ratio are not found statistically significiant in patients and control group at the begining and middle of the treatment (1,84,[3,36-0,51] -1,62,[4,07-0,68], p:0,107), C-reactive protein levels show a statistically significiant decrease in patient group with treatment (p<0,028). Conclusion:Systemic isotretinoin treatment may affect neutrophillymphocyte ratio and C-reactive protein levels in patients. Further studies are needed to clarify this relation.

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Downregulation of S100a7a antimicrobial peptide in acne vulgaris patients after isotretinoin therapy

Cited by 8 publications

References 20 publications

Molecular characterization of chronic cutaneous wounds reveals subregion‐ and wound type‐specific differential gene expression

Molecular characterization of chronic cutaneous wounds reveals subregion‐ and wound type‐specific differential gene expression

Use of Patient-Reported Outcomes in Acne Vulgaris and Rosacea Clinical Trials From 2011 to 2021

Sistemik İsotretinoin Tedavisi Alan Akne Vulgaris Hastalarında Nötrofil- Lenfosit Oranı ve C-Reaktif Protein Düzeyleri

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