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1.
West Afr J Med ; 39(8): 829-835, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36057975

RESUMO

BACKGROUND: Keloids are chronic dermal fibro-proliferative disorders resulting from excessive collagen deposition. Although it is commonly seen in the dark skin, it occurs in other races. It is a disfiguring dermatosis whose epidemiology and clinical pattern should be put into proper perspective in an area where it has not been extensively documented. SUBJECTS AND METHOD: A cross-sectional design that included 120 consenting keloids patients was made at the dermatology and plastic surgery clinics of a tertiary hospital over one year. Keloid was diagnosed clinically, risk factors, locations and patterns of affectation were documented. RESULTS: 120 patients with 192 keloids were seen. The mean age of the patients was 36.3±16.0 years with a slight female preponderance (M: F, 1:1.9). The chest was the commonest site 37 (19.3%), then earlobe 27 (14.1%) and face 21(11.0%). The buttock/feet were the least affected areas. Trauma including ear piercing, shaving, lacerations/cuts were the commonest risk factors 108 (56.2%) for keloid. The commonest observed morphological patterns in descending order of occurrence include flat 61 (31.8%), nodular 54 (28.1%) and superficial spreading 51 (26.6%) type. Flat pattern was commonest in breast and chest areas 35 (71.4%), nodular pattern on earlobes 17 (63.0%), face 11 (52.3%), scalp 3 (50.0%), neck 5 (38.5%), and guttate pattern on the face 3 (14.0%) and back 2 (22.0%). The shoulder 5 (50.0%), arms 7 (58.3%) and back 4 (44.4%) had more of the superficial spreading pattern when the morphology/patterns of keloid in these areas were compared. CONCLUSION: Keloids affects predominantly young adults with single anatomical site being the commonest presentation, with the chest mostly affected and the flat pattern commonly observed. The morphological distinction of keloids and location may influence the choice of treatment modality.


CONTEXTE: Les chéloïdes sont des troubles dermiques chroniques fibro-prolifératifs résultant d'un dépôt excessif de collagène résultant d'un dépôt excessif de collagène. Bien qu'elle soit couramment dans les peaux foncées, elle se produit dans d'autres races. Il s'agit d'une dermatose défigurante dermatose dont l'épidémiologie et le profil clinique doivent être mis en perspective dans une région où elle n'a pas été largement documentée. SUJETS ET MÉTHODE: Une étude transversale incluant 120 patients consentants atteints de chéloïdes a été réalisée dans les cliniques de dermatologie et de chirurgie plastique d'un hôpital tertiaire sur une période d'un an. La chéloïde a été diagnostiquée cliniquement, les facteurs de risque, les localisations et les schémas d'affectation ont été documentés. RÉSULTATS: 120 patients présentant 192 chéloïdes ont été examinés. L'âge moyen des patients était de 36,3±16,0 ans avec une légère prépondérance féminine (M : F,1:1.9). La poitrine était le site le plus fréquent 37 (19,3%), puis le lobe de l'oreille 27 (14,1 %) et le visage 21 (11,0 %). Les fesses et les pieds étaient les zones les moins touchées zones les moins touchées. Les traumatismes, y compris le perçage des oreilles, le rasage, les lacérations/coupures, étaient les facteurs de risque les plus courants.les facteurs de risque les plus courants 108 (56,2 %) pour la chéloïde. Les formes morphologiques les plus courantes morphologiques les plus fréquemment observés, par ordre décroissant de fréquence sont le type plat 61 (31,8 %), le type nodulaire 54 (28,1 %) et le type d'extension superficielle 51 (26,6 %). La forme plate était la plus fréquente dans les zones du sein et de la poitrine.35 (71,4 %), le type nodulaire sur le lobe des oreilles 17 (63,0 %), le visage 11 (52,3 %), cuir chevelu 3 (50,0 %), le cou 5 (38,5 %), et le motif en gouttes sur le visage 3 (14,0 %) et le dos 2 (22,0 %). L'épaule 5 (50,0 %), les bras 7 (58,3 %) (58,3 %) et le dos 4 (44,4 %) présentaient davantage de motifs d'étalement superficiel morphologie/profil de la chéloïde dans ces zones. CONCLUSION: Les chéloïdes touchent principalement les jeunes adultes. site anatomique unique est la présentation la plus courante, le thorax étant le plus souvent touché. La poitrine est la plus touchée et le modèle plat est couramment observé. Le site distinction morphologique des chéloïdes et de leur localisation peut influencer le choix de la modalité de traitement. MOTS CLÉS: Chéloïde, Peau foncée, Épidémiologie, Profil Clinique.


Assuntos
Queloide , Adulto , Estudos Transversais , Orelha Externa/lesões , Orelha Externa/patologia , Orelha Externa/cirurgia , Feminino , Instalações de Saúde , Humanos , Queloide/epidemiologia , Queloide/etiologia , Queloide/patologia , Pessoa de Meia-Idade , Nigéria/epidemiologia , Adulto Jovem
2.
Front Immunol ; 13: 942446, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967426

RESUMO

A keloid is a fibroproliferative disorder of unknown etiopathogenesis that requires ill-defined treatment. Existing evidence indicates that the immune system plays an important role in the occurrence and development of keloid. However, there is still a lack of research on the immune-related signatures of keloid. Here we identified immune-related signatures in keloid and explored their pathological mechanisms. Transcriptomic datasets (GSE7890, GSE92566, and GSE44270) of keloid and normal skin tissues were obtained from the Gene Expression Omnibus database. The overlap of differentially expressed genes and immune-related genes was considered as differentially expressed immune-related genes (DEIGs). Functional analysis, expression, and distribution were applied to explore the function and characteristics of DEIGs, and the expression of these DEIGs in keloid and normal skin tissues was verified by immunohistochemistry. Finally, we conducted interactive network analysis and immune infiltration analysis to determine the therapeutic potential and immune correlation. We identified four DEIGs (LGR5, PTN, JAG1, and DKK1). In these datasets, only GSE7890 met the screening criteria. In the GSE7890 dataset, DKK1 and PTN were downregulated in keloid, whereas JAG1 and LGR5 were upregulated in keloid. In addition, we obtained the same conclusion through immunohistochemistry. Functional analysis indicated that these four DEIGs were mainly involved in stem cell, cell cycle, UV response, and therapy resistance. Through interactive network analysis, we found that these DEIGs were associated with drugs currently used to treat keloid, such as hydrocortisone, androstanolone, irinotecan, oxaliplatin, BHQ-880, and lecoleucovorin. Finally, many immune cells, including CD8+ T cells, resting memory CD4+ T cells, and M1 macrophages, were obtained by immune infiltration analysis. In conclusion, we identified four immune signaling molecules associated with keloid (LGR5, PTN, JAG1, and DKK1). These immune-related signaling molecules may be important modules in the pathogenesis of keloid. Additionally, we developed novel therapeutic targets for the treatment of this challenging disease.


Assuntos
Queloide , Linfócitos T CD8-Positivos/metabolismo , Humanos , Queloide/patologia , Macrófagos/metabolismo , Transdução de Sinais , Transcriptoma
3.
J Agric Food Chem ; 70(35): 10782-10793, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36005946

RESUMO

Glabridin (Gla) is a typical flavonoid isolated from the Glycyrrhiza glabra with various bioactivities and is a common additive in many cosmetics. In our study, we evaluated the antiscarring effect of Gla from G. glabra in a rabbit ear hyperplastic scar model. Hematoxylin and eosin staining and Masson staining were applied to determine the pathological changes and collagen fibers of scar tissue in rabbits. The results suggested that Gla could reduce rabbit ear scar hyperplasia, inhibit inflammation, and decrease collagen production. Furthermore, the in vitro cell experiments were applied to determine the effects of Gla on human keloid fibroblasts (HKFs), and we observed that Gla suppressed the HKF cells' proliferation via inducing apoptosis. Subsequently, we found that Gla reduced collagen production in HKF cells. The further molecular mechanisms investigations suggested that Gla played a therapeutic role against keloid by attenuating PI3K/Akt and TGFß1/SMAD pathways. Our study would be beneficial for extending the applications of the known sweet plant of G. glabra.


Assuntos
Glycyrrhiza , Queloide , Animais , Colágeno/metabolismo , Fibroblastos , Glycyrrhiza/metabolismo , Humanos , Isoflavonas , Queloide/tratamento farmacológico , Queloide/metabolismo , Queloide/patologia , Fenóis , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Coelhos , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
4.
J Zhejiang Univ Sci B ; 23(8): 699-704, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35953762

RESUMO

Keloids are a common type of pathological scar as a result of skin healing, which are extremely difficult to prevent and treat without recurrence. The pathological mechanism of keloids is the excessive proliferation of fibroblasts, which synthesize more extracellular matrices (ECMs), including type I/III collagen (COL-1/3), mucopolysaccharides, connective tissue growth factor (CTGF, also known as cellular communication network factor 2 (CCN2)), and fibronectin (FN) in scar tissue, mostly through the abnormal activation of transforming growth factor-|ß (TGF-|ß)/Smads pathway (Finnson et al., 2013; Song et al., 2018). Genetic factors, including race and skin tone, are considered to contribute to keloid formation. The reported incidence of keloids in black people is as high as 16%, whereas white people are less affected. The prevalence ratio of colored people to white people is 5:1||-||15:1 (Rockwell et al., 1989; LaRanger et al., 2019). In addition, keloids have not been reported in albinism patients of any race, and those with darker skin in the same race are more likely to develop this disease (LaRanger et al., 2019). Skin melanocyte activity is significantly different among people with different skin tones. The more active the melanocyte function, the more melanin is produced and the darker the skin. Similarly, in the same individual, the incidence of keloids increases during periods when melanocytes are active, such as adolescence and pregnancy. Keloids rarely appear in areas where melanocytes synthesize less melanin, such as in the palms and soles. Thus, the formation of keloids seems to be closely related to melanocyte activity.


Assuntos
Exossomos , Queloide , Adolescente , Células Cultivadas , Exossomos/metabolismo , Fibroblastos/metabolismo , Humanos , Queloide/patologia , Melaninas/metabolismo , Melanócitos/metabolismo , Melanócitos/patologia , Projetos Piloto , Pele/metabolismo , Fator de Crescimento Transformador beta/metabolismo
5.
Front Immunol ; 13: 940645, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990663

RESUMO

Keloids, characterized by skin fibrosis and excessive accumulation of extracellular matrix, remain a therapeutic challenge. In this study, we systematically capture the cellular composition of keloids by the single-cell RNA sequencing technique. Our results indicated that there are significant differences in most cell types present between 12 pairs of keloid and adjacent normal tissue. We found that fibroblasts, endothelial cells, mast cells, mural cells, and Schwann cells increased significantly in keloid. The proportion of mesenchymal fibroblast subpopulations in keloids was markedly higher than those in the surrounding normal skin tissue. Furthermore, we found that the immune profiles between two groups varied significantly. The proportion of macrophages in the keloid was significantly elevated compared to the surrounding normal tissue, while cDC2 cells significantly decreased. Hotspot and pseudotime trajectory analysis indicated two modules of macrophage cells (Module2: highly expresses RNASE1, C1QA, CD163, CD14, C1QC, FCGRT, MS4A7; Module10: highly expresses APOC1, CTSB, CTSL, TYROBP), which exhibited the characteristics of tumor-associated macrophages, were upregulated in more-advanced keloid cells. Subsequently, the analysis of cellular communication networks suggested that a macrophage-centered communication regulatory network may exist in keloids and that fibroblasts in keloids may facilitate the transition and proliferation of M2 macrophages, which contributes to further comprehension of the immunological features of keloids. Overall, we delineate the immunology landscape of keloids and present new insights into the mechanisms involved in its formation in this study.


Assuntos
Queloide , Células Cultivadas , Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Humanos , Queloide/patologia , Análise de Sequência de RNA
6.
Acta Biomater ; 150: 22-33, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35914694

RESUMO

Scarring is a major clinical issue that affects a considerable number of patients. The associated problems go beyond the loss of skin functionality, as scars bring aesthetic, psychological, and social difficulties. Therefore, new strategies are required to improve the process of healing and minimize scar formation. Research has highlighted the important role of mechanical forces in the process of skin tissue repair and scar formation, in addition to the chemical signalling. A more complete understanding of how engineered biomaterials can modulate these mechanical stimuli and modify the mechanotransduction signals in the wound microenvironment is expected to enable scar tissue reduction. The present review aims to provide an overview of our current understanding of skin biomechanics and mechanobiology underlying wound healing and scar formation, with an emphasis on the development of novel mechanomodulatory wound dressings with the capacity to offload mechanical tension in the wound environment. Furthermore, a broad overview of current challenges and future perspectives of promising mechanomodulatory biomaterials for this application are provided. STATEMENT OF SIGNIFICANCE: Scarring still is one of the biggest challenges in cutaneous wound healing. Beyond the loss of skin functionality, pathological scars, like keloids and hypertrophic, are associated to aesthetic, psychological, and social distress. Nonetheless, the understanding of the pathophysiology behind the formation of those scars remains elusive, which has in fact hindered the development of effective therapeutics. Therefore, in this review we provide an overview of our current understanding of skin biomechanics and mechanobiology underlying wound healing and scar formation, with an emphasis on the development of novel mechanomodulatory wound dressings with the capacity to offload mechanical tension in the wound environment.


Assuntos
Cicatriz Hipertrófica , Queloide , Materiais Biocompatíveis/uso terapêutico , Cicatriz Hipertrófica/patologia , Humanos , Queloide/patologia , Queloide/prevenção & controle , Mecanotransdução Celular , Pele/patologia , Cicatrização/fisiologia
7.
Oxid Med Cell Longev ; 2022: 7434733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774378

RESUMO

Keloid is a common dermatofibrotic disease with excessive skin fibroblast proliferation. Hydrogen sulfide (H2S) as the third gasotransmitter improves fibrosis of various organs and tissues. Our study is aimed at investigating the effects and possible mechanisms of H2S on skin fibroblast proliferation. Scar tissues from six patients with keloid and discarded skin tissue from six normal control patients were collected after surgery, respectively. Plasma H2S content and skin H2S production in patients with keloid were measured. Keloid fibroblasts and transforming growth factor-ß 1- (TGF-ß 1, 10 ng/mL) stimulated normal skin fibroblasts were pretreated with H2S donor as NaHS (50 µM) for 4 h. Cell migration after scratch was assessed. The expressions of α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), collagen I, and collagen III were detected by immunofluorescence, real-time PCR, and/or Western blot. Intracellular superoxide anion and mitochondrial superoxide were evaluated by dihydroethidium (DHE) and MitoSOX staining, respectively. Mitochondrial membrane potential was detected by JC-1 staining. Apoptotic cells were detected by TDT-mediated dUTP nick end labeling (TUNEL). The expressions of receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) were measured by Western blot. We found that H2S production was impaired in both the plasma and skin of patients with keloid. In keloid fibroblasts and TGF-ß 1-stimulated normal skin fibroblasts, exogenous H2S supplementation suppressed the expressions of α-SMA, PCNA, collagen I, and collagen III, reduced intracellular superoxide anion and mitochondrial superoxide, improved the mitochondrial membrane potential, decreased the positive rate of TUNEL staining, and inhibited RIPK1 and RIPK3 expression as well as MLKL phosphorylation. Overall, H2S suppressed skin fibroblast proliferation via oxidative stress alleviation and necroptosis inhibition.


Assuntos
Sulfeto de Hidrogênio , Queloide , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Fibroblastos/metabolismo , Humanos , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Queloide/metabolismo , Queloide/patologia , Necroptose , Estresse Oxidativo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Superóxidos/metabolismo
8.
Ugeskr Laeger ; 184(25)2022 Jun 20.
Artigo em Dinamarquês | MEDLINE | ID: mdl-35781362

RESUMO

Keloids are pathological scars extending beyond the initial wound's natural borders. The condition occurs as a result of impaired wound healing with excessive collagen deposition. Keloid scars frequently recur, rarely regress, and have a tendency to grow over time. They are aesthetically disfiguring and can be devastating for patients, both physically and emotionally. This review finds that prevention and early intervention are essential for good results. Treatment is often challenging. There are no standardized management guidelines currently available but a combinational therapeutic approach appears to be beneficial.


Assuntos
Queloide , Antiácidos , Colágeno , Humanos , Queloide/patologia , Queloide/prevenção & controle , Penicilinas , Recidiva
9.
Dermatol Ther ; 35(9): e15730, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35871490

RESUMO

Bleomycin is a known chemotherapeutic agent whose beneficial effects have been recently shown in the treatment of keloids and hypertrophic scars, however, it is unclear how effective it is in comparison with corticosteroids. We aimed to compare the safety and efficacy of intralesional bleomycin versus intralesional triamcinolone in the treatment of hypertrophic scars and keloids. Sixty patients were divided into two groups and treated by intralesional injection of triamcinolone (20 mg/ml) or bleomycin (1.5 mg/ml). The treatments were repeated every 3 weeks until the lesions flattened or for a maximum of six sessions. The clinical improvement was evaluated using the Japan scar workshop (JSW) scar scale (JSS) and the physician global assessment of flattening of the lesions. Side effects were also noted and recorded. 55 patients completed the study, 4 patients from the bleomycin group and 1 patient from the triamcinolone group dropped out of the study. In both groups, the total JSS scores decreased significantly after treatment compared to baseline (p < 0.001); however, the difference between groups was not statistically significant after treatment (p = 0.052). Moreover, the degree of flattening of the lesions was comparable between groups (p = 0.933). Side effects in the triamcinolone group were Hypopigmentation(55.2%), atrophy(51.7%), and telangiectasia(41.4%) and in bleomycin group included persistent pain after injection (61.5%), ulceration (69.2%), hyperpigmentation(76.9%), and secondary infection (34.6%). Intralesional bleomycin (1.5 mg/ml) is effective as triamcinolone(20 mg/ml) in the treatment of keloids and hypertrophic scars, however, bleomycin should be used carefully, due to adverse events such as pain, ulceration, and hyperpigmentation.


Assuntos
Cicatriz Hipertrófica , Hiperpigmentação , Queloide , Bleomicina , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/patologia , Humanos , Hiperpigmentação/induzido quimicamente , Injeções Intralesionais , Queloide/tratamento farmacológico , Queloide/patologia , Dor/tratamento farmacológico , Resultado do Tratamento , Triancinolona/efeitos adversos , Triancinolona Acetonida/efeitos adversos
10.
PLoS Genet ; 18(6): e1010168, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35709140

RESUMO

Keloid disorder is a tumour-like disease with invasive growth and a high recurrence rate. Genetic contribution is well expected due to the presence of autosomal dominant inheritance and various genetic mutations in keloid lesions. However, GWAS failed to reveal functional variants in exon regions but single nucleotide polymorphisms in the non-coding regions, suggesting the necessity of innovative genetic investigation. This study employed combined GWAS, RNA-sequence and Hi-C analyses to dissect keloid disorder genetic mechanisms using paired keloid tissues and normal skins. Differentially expressed genes, miRNAs and lncRNAs mined by RNA-sequence were identified to construct a network. From which, 8 significant pathways involved in keloid disorder pathogenesis were enriched and 6 of them were verified. Furthermore, topologically associated domains at susceptible loci were located via the Hi-C database and ten differentially expressed RNAs were identified. Among them, the functions of six molecules for cell proliferation, cell cycle and apoptosis were particularly examined and confirmed by overexpressing and knocking-down assays. This study firstly revealed unknown key biomarkers and pathways in keloid lesions using RNA-sequence and previously reported mutation loci, indicating a feasible approach to reveal the genetic contribution to keloid disorder and possibly to other diseases that are failed by GWAS analysis alone.


Assuntos
Queloide , MicroRNAs , RNA Longo não Codificante , Estudo de Associação Genômica Ampla , Humanos , Queloide/genética , Queloide/patologia , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genética
11.
Zhonghua Shao Shang Za Zhi ; 38(6): 590-594, 2022 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-35764588

RESUMO

In re-cent 20 years, the development of cell biology technology has promoted the research of keloid. Keloid fibroblasts (KFbs) are the main effector cells in keloid, which are closely related to the occurrence and development of keloid. It is significantly different in terms of biological characteristics and gene expression between KFbs and normal fibroblasts. This articles reviews the characteristics of KFbs from multiple perspectives, describing its biological character- istics in details including microstructures, metabolic character- istics, and proliferation properties, and introducing the main characteristics of heterogeneity and genomics of KFbs. The further research on KFbs will help to elucidate the pathogenesis of keloids and provide valuable strategies for the prevention and treatment of keloids.


Assuntos
Queloide , Fibroblastos/metabolismo , Humanos , Queloide/patologia
12.
Am J Case Rep ; 23: e935898, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35724245

RESUMO

BACKGROUND Several factors contribute to keloids in post-operative patients, including skin mechanics, genetics, and inflammatory processes. One of the most widely used treatment modalities for keloidal scars involves the intralesional injection of corticosteroids, such as triamcinolone acetonide (TAC). TAC is a first-line treatment option for keloids due to its proven efficacy and effectiveness in reducing collagen synthesis, glycosaminoglycan synthesis, inflammatory processes, and proliferation of fibroblasts. Some common adverse effects of intralesional corticosteroid injection include localized hypopigmentation, depigmentation, skin atrophy, and lipoatrophy. CASE REPORT In this report, we describe the case of a 3-year-old African American male patient who presented for dermatologic evaluation of a diffused stellate hypopigmentation attributed to intralesional corticosteroid injection following a keloid removal. Specifically, we summarize this case's clinical features, diagnosis, and outcomes. CONCLUSIONS The case illustrates self-limiting hypopigmentation that repigmented successfully without clinical intervention. Although previous reports of corticosteroid injections' adverse effects resulting in hypopigmentation have been published, this condition is uncommon or poorly reported in pediatric patients. This report aims to contribute to our understanding of the effects of administering corticosteroids in pediatric patients by virtue of diversifying the cases reported in the currently available literature.


Assuntos
Hipopigmentação , Queloide , Corticosteroides/uso terapêutico , Criança , Pré-Escolar , Glucocorticoides , Humanos , Hipopigmentação/induzido quimicamente , Injeções Intralesionais , Queloide/induzido quimicamente , Queloide/tratamento farmacológico , Queloide/patologia , Masculino , Resultado do Tratamento , Triancinolona Acetonida/efeitos adversos
13.
Front Immunol ; 13: 883239, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711461

RESUMO

Inflammation plays an active role during the wound healing process. There is a direct association between the extent of injury as well as inflammation and the amount of subsequent cutaneous scarring. Evidence to date demonstrates that high levels of inflammation are associated with excessive dermal scarring and formation of abnormal pathological scars such as keloids and hypertrophic scars. In view of the multiple important cell types being involved in the inflammatory process and their influence on the extent of scar formation, many scar therapies should aim to target these cells in order to control inflammation and by association help improve scar outcome. However, most current treatment strategies for the management of a newly formed skin scar often adopt a watch-and-wait approach prior to commencing targeted anti-inflammatory therapy. Moreover, most of these therapies have been evaluated in the remodelling phase of wound healing and the evaluation of anti-inflammatory treatments at earlier stages of healing have not been fully explored and remain limited. Taken together, in order to minimise the risk of developing a poor scar outcome, it is clear that adopting an early intervention prior to skin injury would be optimal, however, the concept of pre-emptively priming the skin prior to injury has not yet been thoroughly evaluated. Therefore, the aim of this review was to evaluate the available literature regarding scar therapies that aim to target inflammation which are commenced prior to when a scar is formed or immediately after injury, with a particular focus on the role of pre-emptive priming of skin prior to injury in order to control inflammation for the prevention of poor scarring outcome.


Assuntos
Cicatriz Hipertrófica , Queloide , Dermatopatias , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/prevenção & controle , Humanos , Inflamação/patologia , Queloide/patologia , Pele/patologia , Dermatopatias/patologia , Cicatrização
14.
Front Immunol ; 13: 888719, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757697

RESUMO

Keloid is an abnormal fibrotic disease after cutaneous injury characterized by exaggerated scar tissue formation, which often extends beyond the boundaries of the original wound. Although chronic inflammation is known to be associated with the excessive inflammation in keloid tissue, there are few studies on the role of autophagy in the pathogenesis of keloid. In this study, we evaluated the pattern of autophagy in keloid fibroblasts (KF) and normal fibroblasts (NF). Expression of HIF-1α, STAT3 and autophagic flux markers were evaluated in KF and NF. Defective autophagy caused by IL-17 was evaluated, and the relationship between defective autophagy and necroptosis was also examined. The expression of IL-17, HIF-1α and STAT3 was significantly increased in keloid tissue, and autophagosome-to autophagolysosome conversion was defective in KF. IL-17 treatment significantly elevated the expression of STAT3 and HIF-1α in NF and caused defective autophagy, which was reversed by HIF-1α inhibitor. In addition, the defective autophagy was associated with the increased necroptosis and fibrosis. In keloid tissue, the elevated necroptosis marker was confirmed, and with the HIF-1α inhibitor, the defective autophagy, necroptosis and fibrosis was decreased in KF. In conclusion, autophagy was defective in keloid tissue, which was associated with increased necroptosis and fibrosis. The IL-17-STAT3-HIF-1α axis was involved in defective autophagy in KF, and this suggests that targeting the axis could alleviate chronic inflammation in keloid disease.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Interleucina-17 , Queloide , Fator de Transcrição STAT3 , Autofagia , Morte Celular , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Interleucina-17/metabolismo , Queloide/metabolismo , Queloide/patologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
15.
Genomics ; 114(4): 110403, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35709926

RESUMO

BACKGROUND: Keloid is a benign proliferative disease characterized by excessive deposition of extracellular matrix collagen during skin wound healing. The mechanisms of keloid formation have not been fully elucidated, and the current treatment methods are not effective for all keloid patients. Therefore, there is an urgent need to find more effective therapies, and our research focused on identifying characteristic molecular signatures of keloid to explore potential therapeutic targets. METHODS: Gene expression profiles of keloid and control group samples were retrieved from the GEO database. Taking the GSE113619 dataset as the training set, the dataset collected skin tissues from non-lesion sites of healthy and keloid-prone individuals, denoted as Day0. The second sampling was performed 42 days later at the original sampling site of control and keloid groups, denoted as Day42.The 'limma' package and Venn diagram identified differentially expressed genes (DEGs) specific to keloid day42 versus day0 samples. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway functional enrichment, and annotation of the characteristic genes were conducted on the Metascape website. Ingenuity canonical pathways, disease & function enrichment analysis and gene interaction network were performed and predicted in Ingenuity Pathway Analysis (IPA) software. Key module genes related to keloid were filtered out by Weighted Gene Co-expression Network Analysis (WGCNA). We utilized the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to screen the characteristic genes in keloid by the 'glmnet' package. The area under the curve (AUC) of receiver operating characteristic (ROC) was utilized to determine the effectiveness of potential signatures in discriminating keloid samples from normal samples and performed by using the 'pROC' package. The enrich scores of 24 immune cells in each sample were calculated by the single-sample gene set enrichment analysis (ssGSEA) algorithm, and then the Gene Set Variation Analysis (GSVA) was performed. Finally, RNA from 4 normal and 6 keloid samples was extracted, and RT-qPCR and Western Blot validated the expression of characteristic genes. RESULTS: A total of 640 DEGs specific to keloid day42 versus day0 samples were detected. 69 key module genes were uncovered and implicated in 'NCAM signaling for neurite out-growth', 'oncogenic MAPK signaling', 'transmission across chemical synapses' pathways, and the mitotic cell cycle-related processes. Five characteristic genes (MTUS1, UNC5C, CEP57, NAA35, and HOXD3) of keloid were identified by LASSO, and among which UNC5C and HOXD3 were validated by ROC plot in external dataset, RT-qPCR and Western Blot in validation samples. The result of ssGSEA indicated that the infiltration of neutrophils showed a relatively higher abundance and natural killer cells with relatively low enrichment in the keloid group compared to the control group. UNC5C was correlated with more immune cells compared with other characteristic genes. CONCLUSION: In this study, characteristic genes associated with keloid were identified by bioinformatic approaches and verified in clinical validation samples, providing potential targets for the diagnosis and treatment of keloid.


Assuntos
Proteínas de Homeodomínio/metabolismo , Queloide , Fatores de Transcrição/metabolismo , Biologia Computacional/métodos , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Queloide/tratamento farmacológico , Queloide/genética , Queloide/patologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/uso terapêutico , Receptores de Netrina/genética , Proteínas Nucleares/genética , Proteínas Supressoras de Tumor/genética
16.
Radiother Oncol ; 173: 146-153, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35688397

RESUMO

BACKGROUND AND PURPOSE: Adjuvant electron beam radiation therapy after keloid excision has been proven as highly effective in reducing local recurrence. We performed a meta-analysis of studies on hypofractionated electron beam radiation therapy after keloid excision based on accurate radiation dose information to provide a more precise estimate of the effect of the biologically effective dose (BED) on recurrence rate. MATERIALS AND METHODS: A literature search was performed in PubMed, Embase, and the Cochrane Library for the period from 1990 to December 2021. Studies that provided information on the recurrence rate for the exact prescription dose were selected for analysis. The recurrence rate with respect to the BED was evaluated using forest plots and the best-fit lines on scatter plots. RESULTS: From the 28 studies that were included for analysis, a total of 37 radiation dose datasets were extracted and 3128 excised keloids were identified. The recurrence rate for all sites and for the ear was 0.16 (95% confidence interval, 0.12-0.21; P < 0.01) and 0.11 (95% confidence interval, 0.06-0.20; P < 0.01), respectively. The estimated recurrence rate for all sites and the ear was calculated as "-1.992 + 1018.226/BED2" or "2.982 + 330.51/BED10" and "-16.8 + 1597.84/BED2" or "-14.65 + 656.58/BED10," respectively. CONCLUSIONS: Postoperative radiation therapy with higher BED resulted in lower recurrence rates. As expected, ear keloids had lower estimated recurrence rates than all keloids at all sites. We derived a model for estimating the recurrence rate using the dose fractionation scheme.


Assuntos
Queloide , Fracionamento da Dose de Radiação , Elétrons , Humanos , Queloide/patologia , Queloide/radioterapia , Queloide/cirurgia , Período Pós-Operatório , Recidiva , Resultado do Tratamento
17.
Appl Immunohistochem Mol Morphol ; 30(6): 453-458, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35510745

RESUMO

Immunohistochemical staining can be of great utility in differentiating various cutaneous spindle cell neoplasms, particularly when the histomorphologic appearance of the lesions is inconclusive. Nuclear staining for ETS-related gene (ERG), a highly sensitive endothelial cell marker, has seldom been studied in the context of cutaneous spindle cell neoplasms. Little is known about its specificity for vascular differentiation. In this pilot study, immunohistochemical analysis for ERG was performed on 15 dermatofibromas (DF), 10 keloids, and 9 dermatofibrosarcoma protuberans (DFSP) tumors. Consistent nuclear expression of ERG was found in DF [100% (15/15) of the lesions demonstrated >50% labeling of tumor cells with moderate to strong intensity]. However, ERG expression was largely absent in DFSP [89% (8/9) of the lesions demonstrating <50% labeling staining, generally of mild intensity] and hypertrophic scars-keloids [80% (8/10) without expression]. On the basis of the results of this pilot study, immunohistochemical staining for ERG may prove useful in helping to differentiate DF from DFSP and hypertrophic scars in the context of partial biopsy sampling. If replicated in a larger number of samples, this finding could mitigate the use of costly sequencing panels and potentially avoid unnecessary reexcisions in certain contexts.


Assuntos
Cicatriz Hipertrófica , Dermatofibrossarcoma , Histiocitoma Fibroso Benigno , Queloide , Neoplasias Cutâneas , Biomarcadores Tumorais/metabolismo , Cicatriz Hipertrófica/diagnóstico , Cicatriz Hipertrófica/patologia , Dermatofibrossarcoma/metabolismo , Diagnóstico Diferencial , Histiocitoma Fibroso Benigno/diagnóstico , Histiocitoma Fibroso Benigno/genética , Histiocitoma Fibroso Benigno/metabolismo , Humanos , Queloide/patologia , Projetos Piloto , Neoplasias Cutâneas/patologia , Regulador Transcricional ERG
19.
Ann Plast Surg ; 88(3 Suppl 3): S194-S196, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35513318

RESUMO

BACKGROUND: Keloid formation occurs with increased incidence in African Americans and Afro-Caribbeans when compared with other ethnic populations. Although surgical management and nonsurgical management of keloids are mainstays of treatment, there are significant variations within studies comparing the efficacy of intraoperative steroid injection, postoperative radiotherapy, or a combination of both modalities. The purpose of our study is to evaluate the efficacy of different treatment modalities used for treatment of keloids and to determine their recurrence in a select Afro-Caribbean population. METHODS: A retrospective review of the plastic surgery case list from January 2015 to October 2019 was conducted, with identification of 46 Afro-Caribbean and African American patients with 56 keloids. Each patient was contacted to determine whether they had experienced recurrence of their keloid(s). Eighteen patients were lost to follow-up, resulting in 28 patients with 35 keloids included in our study. The treatment protocol involved surgical excision for all keloids, with selective additional triamcinolone 40 mg/mL injection intraoperatively, immediate postoperative radiotherapy, or intraoperative triamcinolone injection with postoperative radiotherapy. Recurrence rates between the different treatment groups were calculated, and statistical analyses were performed using IBM SPSS Statistics, with a value of P < 0.05 deeming statistical significance. RESULTS: Our study demonstrates that postoperative recurrence rates of primary and secondary keloids were 43% and 58%, respectively. Results of recurrence rate varied by specific treatment modality; keloid excision yielded a rate of only 54%, keloid excision with postoperative radiation yielded a rate of 83%, keloid excision with intraoperative triamcinolone injection yielded a rate of 33%, and keloid excision with a combination of intraoperative triamcinolone injection and postoperative radiation yielded a rate of 33%. CONCLUSION: Patients of Afro-Caribbean and African American ethnicity are more heavily affected by the formation of keloids compared with other population groups. Results of varying modalities for keloid management demonstrate that patients who received a combination of excision with intraoperative triamcinolone injection, with or without postoperative radiation, had the lowest recurrence rates compared with other treatment protocols including excision alone and excision with postoperative radiation only.


Assuntos
Queloide , Afro-Americanos , Região do Caribe , Humanos , Queloide/patologia , Queloide/cirurgia , Recidiva , Resultado do Tratamento , Triancinolona
20.
J Dermatol Sci ; 106(2): 111-118, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35491288

RESUMO

BACKGROUND: Abnormal expression of long non-coding RNA (lncRNA) has been proved to be related to the formation of keloid. Homeobox A11 antisense (HOXA11-AS) has been found to be a significantly upregulated lncRNA in keloid tissues. OBJECTIVE: To explore the mechanism of HOXA11-AS regulates keloid formation. METHODS: Primary fibroblasts were isolated from keloid tissues and normal skin tissues. The expression of HOXA11-AS, microRNA (miR)-188-5p and vascular endothelial growth factor A (VEGFA) was determined using quantitative real-time PCR (qRT-PCR). Cell counting kit 8 (CCK8) assay, EdU staining, flow cytometry and wound healing assay were performed to assess the proliferation, cell cycle process, apoptosis and migration of keloid fibroblasts. Importantly, some marker protein levels and VEGFA protein level were examined by western blot (WB) analysis. The interaction between miR-188-5p and HOXA11-AS or VEGFA was confirmed using dual-luciferase reporter assay, RNA pull-down assay and RIP assay. Animal experiments were performed to further confirm the role of HOXA11-AS in keloid growth. RESULTS: HOXA11-AS was markedly upregulated in keloid tissues and fibroblasts. Knockdown of HOXA11-AS repressed the proliferation, cell cycle process, migration and promoted the apoptosis of keloid fibroblasts. Further analysis suggested that HOXA11-AS could sponge miR-188-5p to positively regulate VEGFA. The inhibition of HOXA11-AS silencing on the biological functions of keloid fibroblasts could be reversed by miR-188-5p inhibitor. In addition, VEGFA overexpression also abolished the suppressive effect of miR-188-5p on the biological functions of keloid fibroblasts. Interferences of HOXA11-AS suppressed keloid growth in vivo. CONCLUSION: HOXA11-AS might regulate the miR-188-5p/VEGFA axis to promote keloid formation.


Assuntos
Queloide , MicroRNAs , RNA Longo não Codificante , Animais , Movimento Celular/genética , Proliferação de Células/genética , Fibroblastos/metabolismo , Queloide/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
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