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Introdução: Atualmente, a aplicação de triancinolona intralesional com a excisão cirúrgica é considerada o tratamento mais satisfatório para queloides, com baixa taxa de recorrência. Método: Realizado estudo de casos contemplando cirurgias reparadoras de pacientes com queloides em lóbulos de orelhas bilateralmente, operados pelo mesmo cirurgião plástico no período de julho de 2018 a janeiro de 2021 no Hospital Regional de Sobradinho em Brasília-DF. Ressecou-se parcialmente a cicatriz queloideana (intralesional), deixando margens de queloide na ferida operatória e comparou-se com a resposta após ressecção total (justalesional) de uma outra cicatriz em um mesmo paciente. Foi realizada aplicação de triancinolona no pré-operatório, com total de 4 aplicações a intervalos de 4 semanas entre cada sessão e no pós-operatório imediato, mantendo aplicação a cada 30 dias por 6 meses. Nenhum paciente havia realizado tratamentos prévios para queloides. As cicatrizes foram avaliadas no pós-operatório pelo cirurgião principal por um período de 12 meses. Resultados: Quatro de 11 pacientes tiveram algum tipo de recidiva, totalizando 36% de recidiva em nosso trabalho. A excisão total do queloide (orelha esquerda) teve mais recidivas do que o lado contralateral em que foi deixada margem de 1mm de queloide na cicatriz (orelha direita). Conclusão: No presente estudo observamos que, quando associada ao tratamento com triancinolona no pré, intra e pós-operatório, a excisão parcial do queloide apresentou menores taxas de recidiva local quando comparada à excisão total do queloide.
Introduction: Currently, the application of intralesional triamcinolone with surgical excision is considered the most satisfactory treatment for keloids, with a low recurrence rate. Method: A case study was carried out covering reconstructive surgeries for patients with bilateral earlobe keloids, operated by the same plastic surgeon from July 2018 to January 2021 at the Hospital Regional de Sobradinho in Brasília-DF. The keloid scar (intralesional) was partially resected, leaving keloid margins in the surgical wound, and compared with the response after total resection (juxtalesional) of another scar in the same patient. Triamcinolone was applied preoperatively, with a total of 4 applications at intervals of 4 weeks between each session and in the immediate postoperative period, maintaining application every 30 days for 6 months. No patient had undergone previous treatments for keloids. Scars were evaluated postoperatively by the primary surgeon over a period of 12 months. Results: Four of 11 patients had some type of recurrence, totaling 36% of recurrence in our study. Total excision of the keloid (left ear) had more recurrences than the contralateral side where a 1mm margin of keloid was left in the scar (right ear). Conclusion: In the present study, we observed that when associated with treatment with triamcinolone pre-, intra-, and postoperatively, partial excision of the keloid presented lower rates of local recurrence when compared to total excision of the keloid.
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Introdução: Cicatrizes hipertróficas e queloides são tipos de cicatrizes excessivas de cicatrização anormal da pele. Galectina-3 (gal-3) é uma proteína da família das lectinas capaz de identificar carboidratos, que podem se combinar e atuar em diversas moléculas. Na literatura, a ação da gal-3 como principal agente regulador da fibrogênese já foi descrita, sendo atualmente utilizada na terapia antifibrótica de diversos órgãos como pulmão e fígado. O objetivo deste estudo piloto foi mostrar resultados preliminares encontrados na expressão de gal-3 em cicatrizes exacerbadas. Método: Foram coletadas 20 amostras de biópsias de cicatrizes excessivas (16 queloides e 4 cicatrizes hipertróficas) e 9 amostras de cicatrizes normais de 22 mulheres e 7 homens. Essas amostras foram processadas para análise histopatológica de rotina por imuno-histoquímica para detectar gal-3. As células positivas para gal-3 foram quantificadas pelo método estereológico utilizando uma grade de 36 pontos. Resultados: A imuno-histoquímica mostrou alta expressão de gal-3 em células endoteliais e epiteliais de todas as amostras de cicatrizes, bem como expressão em células distribuídas pela derme. Maior expressão de gal-3 foi encontrada em amostras de queloides (28% de células positivas) em comparação com cicatrizes normais (18%) e hipertróficas (22%) (p=0,0075). Os resultados foram obtidos de um pequeno número de pacientes, por se tratar de um estudo piloto. Conclusão: Os dados sugerem que a gal-3 participa do processo de cicatrização e, devido à sua maior presença em amostras de queloides, pode ser um potencial biomarcador para formação de queloides e um alvo terapêutico promissor a ser explorado.
Introduction: Hypertrophic scars and keloids are types of excessive scars from abnormal skin healing. Galectin-3 (gal-3) is a protein from the lectin family capable of identifying carbohydrates, which can combine and act on different molecules. In the literature, the action of gal-3 as the main regulatory agent of fibrogenesis has already been described and is currently used in anti-fibrotic therapy for various organs such as the lung and liver. The objective of this pilot study was to show preliminary results found in the expression of gal-3 in exacerbated scars. Method: Twenty biopsy samples from excessive scars (16 keloids and 4 hypertrophic scars) and 9 samples from normal scars were collected from 22 women and 7 men. These samples were processed for routine histopathological analysis by immunohistochemistry to detect gal-3. Gal-3 positive cells were quantified by the stereological method using a 36-point grid. Results: Immunohistochemistry showed high expression of gal-3 in endothelial and epithelial cells of all scar samples, as well as expression in cells distributed throughout the dermis. Higher gal-3 expression was found in keloid samples (28% positive cells) compared to normal (18%) and hypertrophic (22%) scars (p=0.0075). The results were obtained from a small number of patients, as this was a pilot study. Conclusion: The data suggest that gal-3 participates in the healing process and, due to its greater presence in keloid samples, it may be a potential biomarker for keloid formation and a promising therapeutic target to be explored.
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Introdução: Cicatrizes visíveis podem acarretar agravos, sejam estéticos, psicológicos, funcionais ou sociais, principalmente de grande extensão e volume, como os queloides. A descoberta de novos tratamentos de queloides não é fácil, visto a presença de alguns entraves metodológicos e éticos, sendo uma área pouco explorada. A toxina botulínica tem sido apresentada como alternativa terapêutica em estudos nacionais e internacionais, sendo necessária uma compilação e destaque dos principais estudos que possam subsidiar a prática clínica. Assim, o objetivo foi apresentar uma revisão de escopo sobre a utilização terapêutica da toxina botulínica para o tratamento de cicatrizes queloides. Método: A revisão foi realizada através da estratégia PICO e utilizando o Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. Foi realizada nas bases de dados PubMed/ Medline, Biblioteca Virtual em Saúde e SciELO, considerando estudos do período de 2016 até setembro de 2021. Resultados: Foram encontrados 34 artigos no geral relacionados ao tema. Após filtragem e seleção, a revisão foi construída com apoio de 5 artigos. Os estudos variaram entre coorte, relatos de caso, ensaio clínico randomizado e caso-controle. Foi possível observar como principais resultados a ação a curto prazo da toxina botulínica na redução de queloides, maior efetividade na redução dos sintomas e possibilidades de utilização clínica para diferentes populações e manifestações clínicas. Conclusão: O mecanismo de ação da toxina botulínica pode facilitar o tratamento de queloides e redução de sintomas, sendo necessários estudos mais robustos para definição de protocolos cínicos de gestão de cicatrizes.
Introduction: Visible scars can cause problems, whether aesthetic, psychological, functional, or social, mainly of great extension and volume, such as keloids. The discovery of new treatments for keloids is not easy, given the presence of some methodological and ethical obstacles, and it is an area that is little explored. Botulinum toxin has been presented as a therapeutic alternative in national and international studies, requiring a compilation and highlighting of the main studies that can support clinical practice. Thus, the objective was to present a scoping review on the therapeutic use of botulinum toxin for the treatment of keloid scars. Method: The review was carried out using the PICO strategy and using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. It was carried out in the PubMed/ Medline, Virtual Health Library, and SciELO databases, considering studies from 2016 to September 2021. Results: Overall, 34 articles related to the topic were found. After filtering and selection, the review was constructed with the support of 5 articles. The studies varied between cohorts, case reports, randomized clinical trials, and casecontrol. It was possible to observe as main results of the short-term action of botulinum toxin in reducing keloids, greater effectiveness in reducing symptoms, and possibilities of clinical use for different populations and clinical manifestations. Conclusion: The mechanism of action of botulinum toxin can facilitate the treatment of keloids and reduce symptoms, requiring more robust studies to define effective scar management protocols.
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BACKGROUND:There are many studies focusing on keloid scars,but the pathogenesis is not fully understood.In recent years,there have been some new research advances in the pathogenesis of keloids,including transforming growth factor-β(TGF-β)/Smad signaling pathway,ischemic hypoxia,hypoxia-inducible factor 1(HIF-1),and mitogen-activated protein kinase(MAPK)pathway.The TGF-β/Smad pathway is now more clearly studied,and activation of the TGF-β/Smad pathway promotes the development of keloid scars. OBJECTIVE:To review the TGF-β/Smad signaling pathway and evaluate the main therapeutic strategies targeting this pathway,with the aim of contributing to the development of more effective clinical treatments. METHODS:PubMed and Web of Science,CNKI and WanFang databases were searched by computer for relevant literature published from January 2017 to April 2023 with the search terms of"keloid,fibroblasts,TGF-β/Smad,extracellular matrix,collagen,treatment measures"in English and Chinese.Seventy-two articles were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The mechanism of TGF-β/Smad signaling pathway in the occurrence and development of keloids is summarized:TGF-β1 and TGF-β2 are overexpressed in keloids,while TGF-β3 shows antifibrotic effects.Smad2/3 and Smad1/5/8 are combined with Smad4 to form a complex that enters the nucleus and plays a fibrotic role,while Smad6/7 can inhibit keloid hyperplasia.The TGF-β/Smad signaling pathway is currently the most clearly studied pathway in keloids,and there are many pathways targeted to inhibit the activation of this pathway,which can inhibit the occurrence and development of keloids to a greater extent.Currently,there is no single clinical gold standard treatment for keloids,and inhibition of the TGF-β/Smad pathway alone cannot completely inhibit the development of keloids.A comprehensive consideration of the association between all systemic systems and keloids is needed.Although many promising targets have been identified in the fibrosis cascade,more research is needed to translate this into targeted therapies in the clinic.
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SUMMARY: Keloid scar is a unique benign fibroproliferative tumor of the human skin. Previously, it was reported that early growth response 1 (EGR1), a transcription factor, promotes keloid fibrosis; however, the mechanism by which EGR1 modulates keloid formation was not elaborated. In this research, the specific function and the microRNA (miRNA) regulatory network of EGR1 in keloids was examined. Keloid fibroblasts (KFs) were transfected with EGR1-small interfering RNA (siEGR1), EGR1-overexpression plasmid (pcDNA3.1-EGR1), and microRNA (miR-183-5p)-mimics to regulate the expression of EGR1 and miR-183-5p. The study employed dual-luciferase reporter assays to explore the targeting regulation of miR-183-5p on EGR1. Additionally, Western blotting, flow cytometry, qRT-PCR, cell count kit-8 (CCK-8), transwell, and wound healing assays, and RNA sequencing were conducted. EGR1 was upregulated in KFs, and EGR1 silencing diminished proliferation, fibrosis, migration, invasion, and apoptosis of cells. In KFs, the expression of miR- 183-5p was reduced, leading to the inhibition of cell proliferation, migration, and invasion. Conversely, it enhanced apoptosis. By targeting EGR1, miR-183-5p partially counteracted the impact of EGR1 on migration, invasion, and fibrosis in KFs. The findings imply that miR-183-5p suppresses keloid formation by targeting EGR1. As a result, EGR1 holds promise as a potential therapeutic target for preventing and treating keloids.
La cicatriz queloide es un tumor fibroproliferativo benigno único de la piel humana. Anteriormente, se informó que la respuesta de crecimiento temprano 1 (EGR1), un factor de transcripción, promueve la fibrosis queloide; sin embargo, no se explicó el mecanismo por el cual EGR1 modula la formación de queloides. En esta investigación, se examinó la función específica y la red reguladora de microARN (miARN) de EGR1 en queloides. Se transfectaron fibroblastos queloides (KF) con ARN de interferencia pequeño de EGR1 (siEGR1), plásmido de sobreexpresión de EGR1 (pcDNA3.1-EGR1) y miméticos de microARN (miR-183-5p) para regular la expresión de EGR1 y miR-183. -5p. El estudio empleó ensayos de indicador de luciferasa dual para explorar la regulación dirigida de miR-183-5p en EGR1. Además, se realizaron pruebas de transferencia Western, citometría de flujo, qRT-PCR, kit de recuento celular-8 (CCK-8), transwell y curación de heridas, y secuenciación de ARN. EGR1 estaba regulado positivamente en KF, y el silenciamiento de EGR1 disminuyó la proliferación, fibrosis, migración, invasión y apoptosis de las células. En KF, la expresión de miR- 183-5p se redujo, lo que llevó a la inhibición de la proliferación, migración e invasión celular. Por el contrario, mejoró la apoptosis. Al apuntar a EGR1, miR-183-5p contrarrestó parcialmente el impacto de EGR1 en la migración, invasión y fibrosis en KF. Los hallazgos implican que miR-183-5p suprime la formación de queloides al apuntar a EGR1. Como resultado, EGR1 es prometedor como objetivo terapéutico potencial para prevenir y tratar los queloides.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Early Growth Response Protein 1 , Fibroblasts , Keloid/genetics , Keloid/pathology , Wound Healing , Transfection , Down-Regulation , Cell Movement , Blotting, Western , Sequence Analysis, RNA , Apoptosis , MicroRNAs/physiology , Cell Proliferation , Real-Time Polymerase Chain ReactionABSTRACT
Queloides e cicatrizes hipertróficas são lesões formadas a partir da resposta fibroproliferativa anormal ao processo de cicatrização de feridas, gerando uma proliferação excessiva do colágeno nas lesões. Geralmente, predominam em pacientes do sexo feminino e em indivíduos com tons de pele mais escuros. A abordagem terapêutica dessas cicatrizes pode ser indicada de acordo com alguns critérios, como déficit funcional, tamanho e tempo de cicatrização da ferida. Nesse sentido, o presente estudo objetivou realizar uma revisão descritiva da literatura, buscando as evidências de tratamento dos últimos cinco anos neste tema. A revisão foi realizada com base no guideline PRISMA, utilizando as bases de dados PubMed, LILACS, Cochrane Library, SCOPUS, Web of Science e Grey Literature, entre os anos de 2018 e 2022. Foram encontrados 740 artigos, dos quais 16 ensaios clínicos randomizados foram selecionados. Foi evidenciado que manejo do queloide apresenta abordagem multimodal, não havendo um padrão-ouro de tratamento, com taxa de recorrência baixa. Além disso, a terapia combinada de diferentes agentes pareceu ser superior ao uso isolado de métodos terapêuticos no tratamento dessas lesões.
Keloids and hypertrophic scars are lesions formed from the abnormal fibroproliferative response to the wound healing process, generating excessive collagen proliferation in the lesions. They generally predominate in female patients and individuals with darker skin tones. The therapeutic approach to these scars can be indicated according to criteria such as functional deficit, size, and wound healing time. In this sense, the present study aimed to conduct a descriptive review of the literature, seeking evidence of treatment over the last five years. The review was carried out based on the PRISMA guideline, using the databases PubMed, LILACS, Cochrane Library, SCOPUS, Web of Science, and Grey Literature between 2018 and 2022. Seven hundred forty articles were found, of which 16 randomized clinical trials were selected. It was demonstrated that keloid management presents a multimodal approach, with no gold standard of treatment with a low recurrence rate. Furthermore, combined therapy with different agents appeared superior to the isolated therapeutic methods in treating these injuries.
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Keloid is an abnormal scar associated with various skin problems including physical and psychological distress. Keloid is often presented as skin itching, swelling, and pain with possible complications such as recurrent sequelae and stigma. Prevention and treatment of this problem include topical non-invasive and invasive options, such as silicon-based products and corticosteroids which are available in the market. Silicon is stated as a standard product, however, is used more often as a combination with corticosteroids than single use. Effectiveness of both products have been discussed separately in previous studies, making it unclear which one is more superior. Thus, a review is needed to ensure their uses in daily practice and to determine their superiority as a single or combination treatment in order to apply them efficiently. Aim of this study is to compare effectiveness of corticosteroids and silicone products to prevent or treat keloid. Keywords such as "keloid," "corticosteroid," and "silicone products" were used in PubMed, national library of medicine, ResearchGate, and dermatology textbooks. Journals found were analyzed for their validity and reliability before the compilation of this review article. Results found stated that both silicone pharmaceutical products and corticosteroids have their own benefits and risks. In addition, according to their treatment phase, they can be used as single or combination treatment. However, due to limited existing studies found, further research is necessary.
ABSTRACT
Keloid is an abnormal scar associated with various skin problems including physical and psychological distress. Keloid is often presented as skin itching, swelling, and pain with possible complications such as recurrent sequelae and stigma. Prevention and treatment of this problem include topical non-invasive and invasive options, such as silicon-based products and corticosteroids which are available in the market. Silicon is stated as a standard product, however, is used more often as a combination with corticosteroids than single use. Effectiveness of both products have been discussed separately in previous studies, making it unclear which one is more superior. Thus, a review is needed to ensure their uses in daily practice and to determine their superiority as a single or combination treatment in order to apply them efficiently. Aim of this study is to compare effectiveness of corticosteroids and silicone products to prevent or treat keloid. Keywords such as "keloid," "corticosteroid," and "silicone products" were used in PubMed, national library of medicine, ResearchGate, and dermatology textbooks. Journals found were analyzed for their validity and reliability before the compilation of this review article. Results found stated that both silicone pharmaceutical products and corticosteroids have their own benefits and risks. In addition, according to their treatment phase, they can be used as single or combination treatment. However, due to limited existing studies found, further research is necessary.
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Introduction: Keloids are one of the most aggressive spectrums of healing disorders. They have a unique pathophysiology and multiple specific genetic and cellular factors, which have not yet been fully elucidated. So far, literature reviews have found the influence of genetics, injury site, and ethnicity on the incidence and rate of recurrence. Furthermore, the need to associate an adjuvant method with surgical excision has already been verified, but the best therapy has yet to be defined. Method: A retrospective analysis of medical records was carried out to assess the profile of patients who underwent postoperative radiotherapy with an electron beam to treat keloids at the Hospital das Clínicas da Faculdade de Medicina de Botucatu between 2015 and 2019. Results: Data from 131 patients were evaluated, with 269 keloid scars treated. The average duration of treatment was 51 days, and the number of sessions was 17. White patients were predominant (78%) and women (70%), with surgical incision being the main cause of formation (49%) and ear the most identified location (33%). Women were more likely to complete the proposed treatment (p=0.04), while non-literates completed less than those who had at least completed primary or secondary education (p<0.0001). Conclusion: Postoperative radiotherapy for keloid scars is a well-established treatment in the literature and an important tool for plastic surgeons. Knowing the profile of patients who need this therapy is essential to create methods that improve adherence and results.
Introdução: Os queloides correspondem a um dos espectros mais agressivos dos distúrbios da cicatrização. Possuem fisiopatologia ímpar e múltiplos fatores genéticos e celulares específicos, ainda não totalmente elucidados. Até o momento, revisões literárias encontraram influência da genética, local da lesão e etnia sobre a incidência e taxa de recorrência. Ademais, já foi constatada a necessidade de associação de um método adjuvante com a excisão cirúrgica, mas ainda sem definição da melhor terapia. Método: Realizada uma análise retrospectiva de prontuários para avaliação do perfil dos pacientes submetidos a radioterapia pós-operatória com feixe de elétrons para o tratamento de queloides no Hospital das Clínicas da Faculdade de Medicina de Botucatu, entre 2015 e 2019. Resultados: Foram avaliados os dados de 131 pacientes, com um total de 269 cicatrizes queloideanas tratadas. A média da duração do tratamento foi de 51 dias e do número de sessões, de 17. Houve predominância de pacientes brancos (78%) e de mulheres (70%), sendo incisão cirúrgica a principal causa de formação (49%) e a orelha a localização mais identificada (33%). As mulheres tiveram mais chance de completar o tratamento proposto (p=0,04), enquanto os não alfabetizados completaram menos do que aqueles que tinham pelo menos ensino fundamental ou médio completo (p<0,0001). Conclusão: A radioterapia pós-operatória em cicatrizes queloideanas é um tratamento consagrado na literatura e uma importante ferramenta do cirurgião plástico. Conhecer o perfil dos pacientes que necessitam desta terapia é fundamental para criar métodos que melhorem a adesão e o resultado da mesma.
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Background: Keloids are a common problem with significant recurrence. Despite many options available, there is no standard acceptable treatment for keloid. This study has compared the intralesional triamcinolone acetonide and a combination of 5-fluorouracil in the treatment of keloids. Methods: This is a randomized study. 60 patients were randomly allocated into two groups. Group 1-TAC+5FU, Group 2-TAC alone. The intralesional injection was given every 3 weeks till 24 weeks. Results: There was a reduction in scar height, vascularity, pigmentation, and pliability. Improvement in terms of height, vascularity, and pliability was faster with TAC+5FU. Conclusion: TAC+5FU combination was effective in keloids in comparison to Triamcinolone Acetonide (TAC) alone. The combination offered the balanced benefits of faster and more effective responses.
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Resumen El acné queloide nucal es una forma crónica de foliculitis cicatricial, caracterizada por el desarrollo de papulo-pústulas que se convierten en queloides cuyo proceso fisiopatológico no está bien dilucidado. Se presenta un paciente de 19 años, con antecedente familiar de acné queloideo nucal, cuya aparición es posterior al ingreso de una bacteria en el cuero cabelludo. El caso se reporta por la rara frecuencia de la enfermedad y como conocimiento de una posible activación de la enfermedad por el ingreso de una bacteria al organismo del paciente. En este caso, se realiza una revisión breve del tema y resalta la exacerbación del proceso inflamatorio y empeoramiento de la enfermedad con medicina alternativa usada deliberadamente por familiares del paciente.
Abstract Keloid acne nuchae is a chronic form of cicatricial folliculitis, characterized by the development of papules, pustules, and keloid-like plaques which pathophysiological process is not well elucidated. We report a 19-year-old patient, with a family backgroundof keloid acne nuchae, whose appearance is after the entry of a bacterium into the scalp. The case is also reported due to the rare frequency of the disease and as knowledge of a possible activation of the disease by the entry of a bacterium into the patient's organism. In this case, a brief review of the subject is made and the exacerbation of the inflammatory process and worsening of the disease with alternative medicine deliberately used by the patient's relatives is emphasized.
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Objective:To investigate the effect of gallic acid on the morphology, proliferation and cell cycle of keloid fibroblasts, as well as on collagen contraction and the transforming growth factor-β (TGF-β) /Sma- and Mad-related proteins (Smads) signaling pathway, and to explore the role and mechanisms of action of gallic acid in the treatment of keloids.Methods:From August to December 2022, 3 keloid tissue samples were collected from 3 patients with clinically and pathologically confirmed keloids after surgery in the Department of Dermatologic Surgery, Wuhan No.1 Hospital. Primary fibroblasts were isolated and cultured by using the tissue culture method, and 3- to 8-passage fibroblasts were used for subsequent experiments. Cultured keloid fibroblasts were divided into 4 groups: low-, medium- and high-dose gallic acid groups treated with 0.025, 0.05 and 0.1 mg/ml gallic acid respectively, and a control group cultured with Dulbecco′s modified Eagle′s medium (DMEM) containing 10% fetal calf serum. After 24-, 48-, and 72-hour treatment, cellular proliferative activity was evaluated by cell counting kit 8 (CCK8) assay, and collagen contraction by using a three-dimensional culture method. After 24-hour treatment in the above groups, pictures were taken using a differential interference inverted fluorescence microscope, and changes in the cell cycle were analyzed by flow cytometry. Some keloid fibroblasts were divided into 2 groups: an experimental group (high-dose gallic acid group) treated with 0.1 mg/ml gallic acid, and a control group cultured with DMEM containing 10% fetal calf serum. After 24-hour treatment, enzyme-linked immunosorbent assay (ELISA) was performed to determine the changes in supernatant concentrations of TGF-β1, TGF-β2, and TGF-β3 in the two groups, real-time fluorescence-based quantitative PCR to detect the relative mRNA expression levels of TGF-β1, TGF-β2, TGF-β3, Smad2, Smad3, Smad4, and α-smooth muscle actin (α-SMA). Statistical analysis was carried out using t test, one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Compared with the control group, the gallic acid groups showed gradual changes in the shape of keloid fibroblasts under the microscope as the dose of gallic acid increased, including gradually shrinking cell bodies, enlarged intercellular spaces, cell atrophy, increased number of apoptotic cells, etc. CCK8 assay showed that the cellular proliferative activity changed significantly as the dose of gallic acid increased and the treatment time was prolonged ( Fgroup = 78.31, P < 0.001; Ftime = 4.17, P = 0.037), and the proliferative activity of keloid fibroblasts was significantly lower in the high-dose gallic acid group than in the control group at 24, 48, and 72 hours (all P < 0.05). The three-dimensional culture showed that different degrees of collagen contraction occurred in all groups over time, marked collagen contraction was observed in the control group, and a lower degree of collagen contraction in the gallic acid groups; the collagen contraction indices were significantly lower in the medium- and high-dose gallic acid groups than in the control group at 24, 48, and 72 hours (all P < 0.05). Flow cytometry showed that the cell apoptosis rates were significantly higher in the low-, medium- and high-dose gallic acid groups (38.68% ± 3.05%, 41.82% ± 2.19%, 43.56% ± 3.58%, respectively) than in the control group (12.58% ± 1.56%, all P < 0.001) after 24-hour treatment; compared with the control group, the medium- and high-dose gallic acid groups showed significantly decreased proportions of cells in the G0/G1 phase (both P < 0.01), but significantly increased proportions of cells in the S phase and G2/M phase (all P < 0.05). ELISA revealed that the TGF-β1 concentration was significantly lower in the high-dose gallic acid group (758.58 ± 31.42 pg/ml) than in the control group (1 081.30 ± 44.72 pg/ml, t = 11.81, P<0.001), there was no significant difference in the TGF-β2 concentration between the high-dose gallic acid group (71.05 ± 7.40 pg/ml) and the control group (76.43 ± 6.51 pg/ml, t = 1.09, P = 0.317), while the TGF-β3 concentration was significantly higher in the high-dose gallic acid group (5.70 ± 3.87 pg/ml) than in the control group (0.00 ± 0.00 pg/ml, t = 2.94, P = 0.026). As real-time fluorescence-based quantitative PCR revealed, the high-dose gallic acid group showed significantly decreased mRNA expression levels of TGF-β1, Smad2, Smad3, Smad4, and α-SMA (all P < 0.05), but significantly increased mRNA expression level of TGF-β3 ( t = 6.78, P = 0.002) compared with the control group; however, there was no significant difference in the TGF-β2 mRNA expression level between the above two groups ( t = 0.05, P = 0.962) . Conclusion:Gallic acid could change the cell cycle, inhibit the proliferative activity, promote apoptosis and change the shape of keloid fibroblasts, and thus inhibit scar formation and contraction, which may be related to the inhibition of TGF-β/Smads signaling pathway.
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Objective:To explore the abnormally low expression of regulatory T cells (Tregs) in the peripheral blood of patients with keloids, its correlation with the formation and evolution of keloids.Methods:A total of 50 peripheral blood samples of patients diagnosed with keloids were collected in the first diagnosis of Changzhi City People′s Hospital from January 2019 to January 2021 as keloid group, including 22 males and 28 females, with an age range of 18-55 years and an average age of 32.13 years; the control group was normal healthy beauty seekers in the outpatient department of Changzhi People′s Hospital during the same period, and finally 25 peripheral blood samples were also collected, including 15 males and 10 females, with an age range of 18-55 years and an average age of 32.96 years. All patients had 2 ml of venous blood drawn on an empty stomach early in the morning before admission for treatment, and placed in an ethylene diamine tetraacetic acid (EDTA) potassium anticoagulation tube. Fresh peripheral blood samples were generated and sent for examination immediately. Flow cytometry was used to detect the CD4 + , CD25 + , CD127 + cells and low Tregs ratio in peripheral blood of keloid patients ( n=50) and normal healthy people ( n=25); the fluorescence intensity was analyzed, the light scattering data were saved, and Cell Quest Plot was used on the computer after the test. The point diagram and the group square diagram were analyzed by SPSS 24.0 for statistical software analysis; peripheral blood Tregs ratio was expressed as the mean ± standard deviation ( ±s), and the mean comparison between the two groups was conducted by using independent sample t test; multiple groups One-way analysis of variance was used for the comparison of the averages, and the difference was statistically significant at P<0.05. The keloid questionnaire and clinical grading were utilized to deeply analyze the relationship between the Tregs ratio in peripheral blood of keloid patients and the severity of keloid. Results:Compared with the normal control group, the peripheral blood Tregs ratio of the keloid group was significantly reduced [(4.39±1.31)% vs. (6.64±1.83)%, P<0.001]; according to the Sawada score scale, keloids were classified as mild, moderate and severe degrees; the Tregs ratio in peripheral blood of the moderate keloid group was significantly lower than that of the mild keloid group [(4.43±1.23)% vs. (5.37±1.12)%, P<0.05], while in the severe keloid group it was also significantly lower than the moderate keloid group [(3.55±0.97)% vs. (4.43±1.23)%, P<0.05]. Conclusions:The Tregs ratio of peripheral blood in patients with keloids is significantly decreased, suggesting that Tregs cell is one of the biomarkers to reflect the severity of keloids.
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Objective:To investigate effects of the ROCK1 gene on proliferation and migration of and related molecular expression in keloid fibroblasts.Methods:Immunohistochemical technique was used to detect ROCK1 protein expression in human keloids and normal skin tissues, and Western blot analysis was performed to detect the expression of ROCK1, transforming growth factor β1 (TGF-β1) and E-cadherin in keloid tissues. In vitro cultured human keloid fibroblasts (HKFs) were divided into 4 groups: ROCK1 gene overexpression control group (ROCK1 NC group) transfected with ROCK1 gene overexpression control vectors, ROCK1 gene overexpression group (ROCK1 OE group) transfected with ROCK1 gene overexpression vectors, ROCK1 gene knockdown control group (sh NC group) transfected with ROCK1 gene knockdown control vectors, and ROCK1 gene knockdown group (shROCK1 group) transfected with ROCK1 gene knockdown vectors. Cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ROCK1 gene on the survival rate of HKFs, Transwell assay to evaluate the effect on the migration of HKFs, and real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis were conducted to determine the mRNA and protein expression of ROCK1, TGF-β1 and E-cadherin, respectively. Results:Immunohistochemical study showed that ROCK1 protein expression decreased significantly in the human keloid tissues compared with the normal tissues ( t = 6.47, P = 0.003) ; Western blot analysis showed that the expression levels of ROCK1 and E-cadherin significantly decreased ( t = 14.02, 162.20, respectively, both P < 0.001), while TGF-β1 expression significantly increased ( t = 76.01, P < 0.001) in the keloid tissues compared with the expression levels of corresponding proteins in the normal tissues. CCK8 assay showed that the cell activity was significantly lower in the ROCK1 OE group than in the ROCK1 NC group after 24-hour transfection ( t = 3.25, 3.78, P = 0.031, 0.019, respectively), and significantly higher in the shROCK1 group than in the sh NC group ( t = 3.12, 2.79, P = 0.036, 0.049, respectively). Transwell assay showed that the number of migratory cells was significantly lower in the ROCK1 OE group than in the ROCK1 NC group ( t = 5.17, P = 0.004), and significantly higher in the shROCK1 group than in the sh NC group ( t = 9.28, P < 0.001). Compared with the ROCK1 NC group, the ROCK1 OE group showed significantly increased mRNA and protein expression levels of ROCK1 and E-cadherin ( P < 0.05 or < 0.001), but decreased mRNA and protein expression levels of TGF-β1 (both P < 0.001) ; compared with the sh NC group, the shROCK1 group showed significantly decreased mRNA and protein expression levels of ROCK1 and E-cadherin ( P < 0.05 or < 0.001), but significantly increased mRNA and protein expression levels of TGF-β1 ( P = 0.005 or < 0.001) . Conclusions:The ROCK1 gene can inhibit the proliferation and migration of HKFs. Overexpression of the ROCK1 gene can down-regulate the TGF-β1 gene expression and up-regulate the E-cadherin gene expression in HKFs.
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Objective:To determine the expression of transmembrane protein 45A (TMEM45A) in keloid tissues and fibroblasts, and to evaluate its effect on extracellular matrix (ECM) synthesis by keloid-derived fibroblasts (KFs) .Methods:Samples of surgically excised keloid and normal foreskin tissues were collected from the Department of Dermatology and Department of Urology of Yanbian University Hospital from January 2019 to December 2020, and TMEM45A protein expression was determined in keloid tissues and KFs by Western blot analysis. KFs were divided into TMEM45A-specific small interfering RNA (siRNA) group and control siRNA group to be transfected with the TMEM45A-specific siRNA and control siRNA respectively. Then, Western blot analysis was performed to evaluate the effects of down-regulation of the TMEM45A gene on the expression of myofibroblast marker protein (α-smooth muscle actin) and ECM-related proteins.Results:Compared with normal skin tissues (1.00 ± 0.11) and fibroblasts (1.00 ± 0.20), TMEM45A expression levels significantly decreased in keloid tissues (0.26 ± 0.05) and KFs (0.41 ± 0.09), respectively ( t = 10.76, 4.75, P < 0.001, = 0.009, respectively). The expression levels of α-smooth muscle actin, ECM-related type Ⅰ collagen, type Ⅲ collagen, and fibronectin were significantly higher in the TMEM45A-specific siRNA group than in the control siRNA group ( t = -5.98, -4.57, -4.90, -7.19, P = 0.004, 0.010, 0.008, 0.002, respectively) . Conclusion:Lowly expressed TMEM45A in keloids may play an important role in the pathogenesis of keloids by promoting ECM synthesis.
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Objective:To explore the staged treatment of keloid scars and to optimise treatment options.Methods:From June 2005 to June 2019, 629 keloid patients, 253 males and 376 females, aged 9 to 78 years, with a mean age of 31.3±16.8 years, were admitted to the Department of Aesthetic Plastic Surgery of Weifang People's Hospital. Three-stage comprehensive treatment was administered according to the stage of the disease from low to high, and the treatment effect was observed regularly, and the recurrence rate was counted.Results:In stage Ⅰ, 251 patients had local recurrence in 14 cases (5.5%) and 4 cases (1.6%) at 2 years 6 months after treatment, all of whom were cured after re-injection; in stage Ⅱ, 302 patients had local recurrence in 56 cases (18.6%) at 6 months after treatment, 49 patients (87.5%) were cured after re-treatment and 35 patients (11.6%) at 2 years; in stage Ⅲ, at 6 months after treatment, 36 patients (47.3%) had recurrence and 19 patients (25%) had recurrence at 2 years after re-treatment.Conclusions:The results and recurrence rate of keloids after comprehensive treatment are related to their severity, and a more satisfactory outcome can be achieved by staging the treatment according to the stage of the disease.
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Objective:To verify that hypoxia induces epithelial mesenchymal transition in HaCaT cells, and to observe the effect of LncRNA HOTAIR on epithelial mesenchymal transition in HaCaT cells.Methods:From Jan. 2018 to Dec. 2018 in Chinese Academy of Medical Science, HaCaT cells were divided into four groups: group A cultured under normoxia, group B cultured under hypoxia, group C transfected with sh-control cultured under hypoxia, and group D transfected with sh-LncRNA HOTAIR cultured under hypoxia. After 36 hours of culturing, the expression of E-cadherin and vimentin were detected using qPCR and Western blot. The migration of HaCaT cells was evaluated by Transwell assay.Results:The relative quantity of E-cadherin mRNA in the four groups were 3.076±0.271, 1.000±0.089, 1.024±0.222, and 2.595±0.085, while vimentin mRNAs were 1.002±0.183, 4.170±0.279, 4.111±0.477, and 2.412±0.134, respectively. In addition, the Transwll invasion assay showed that numbers of cell migration in the four groups were 32.70±3.93, 125.40±6.26, 120.10±6.79, and 58.24±7.06, respectively.Conclusions:The study suggests that hypoxia promotes epithelial mesenchymal transition in keratinocytes. Furthermore, downregulation of HOTAIR is noted to inhibit epithelial mesenchymal transition of keratinocytes under hypoxia condition.
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Keloid is a fibrous proliferative disease of the skin, and its pathological essence is excessive wound healing caused by excessive fibrosis. Its pathological mechanism is complex and unclear. At present, it is believed that the cellular mechanism of keloids mainly involves inflammatory cells and fibrosis-related cells, as well as cytokines such as growth factors, interleukins, tumor necrosis factor, and matrix metalloproteinase; the molecular mechanism mainly involves TGF-p/Smad pathway, NF-Mo- lecular mechanisms such as kB pathway, STAT3 signaling pathway, MAPK signaling pathway, and focal adhesion kinase. This article reviews the latest research progress on the pathological mechanism of keloids from the perspectives of cells, cytokines, and molecular signaling pathways.
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OBJECTIVE@#To review the research progress of the principle and clinical application of keloid core excision technique.@*METHODS@#The literature on keloid core excision technique at home and abroad in recent years was extensively reviewed, and the principle, development history, indications, advantages and disadvantages of this technique were summarized, and the existing controversies were analyzed.@*RESULTS@#Keloid core excision is a technique to remove the inner fibrous core from the keloid and cover the defect with the keloidal flap. It reduces the wound tension, yields good aesthetic results in the treatment of ear keloids, and reduces the recurrence rate of keloids combining with adjuvant therapies.@*CONCLUSION@#The keloid core excision technique has specific advantages, yet its overall efficacy remains controversial. Further studies are imperative to explore the mechanisms regarding keloid recurrence and the vascular supply principles of the keloidal flap. It is also necessary to define appropriate surgical indications and safety protocols of this technique.
Subject(s)
Humans , Keloid/pathology , Recurrence , Surgical Flaps/pathology , Plastic Surgery Procedures , Treatment OutcomeABSTRACT
Introdução: Calcinose cutânea é uma doença rara caracterizada por precipitações de cristais de cálcio no tecido cutâneo. Pode ser localizada ou generalizada, distrófica, metastática, iatrogênica ou idiopática. Relato do Caso: Paciente feminina, 66 anos, vítima de queimaduras de segundo e terceiro graus por fogo em abdome inferior e coxas aos 8 anos de idade atingindo 25% de superfície corpórea. Após 58 anos, recebeu o diagnóstico de calcinose distrófica na cicatriz da queimadura, contemplado através de biópsia e análise histopatológica. Submetida a exérese cirúrgica associada a rotação de retalho dermogorduroso de abdome superior e enxertia de pele total para correção de cicatrizes. Conclusão: Embora a melhor escolha terapêutica ainda não seja clara, o tratamento de complicações que podem culminar em incapacidade funcional é fundamental para reduzir a morbidade e aumentar a qualidade de vida do paciente.
Introduction: Cutaneous calcinosis is a rare disease characterized by the precipitation of calcium crystals in the skin tissue. It can be localized, generalized, dystrophic, metastatic, iatrogenic, or idiopathic. Case Report: Female patient, 66 years old, victim of second and third-degree burns by fire in the lower abdomen and thighs at 8 years old, reaching 25% of the body surface. After 58 years, she was diagnosed with dystrophic calcinosis in the burn scar, which was confirmed through biopsy and histopathological analysis. She underwent surgical excision associated with rotation of the upper abdomen dermal-fat flap and total skin graft for scar correction. Conclusion: Although the best therapeutic choice is still unclear, treating complications leading to functional disability is essential to reduce morbidity and increase the patient's quality of life.