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1.
Int Wound J ; 21(4): e14851, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563121

RESUMO

Scarring following oral and maxillofacial trauma can have significant aesthetic and functional repercussions. Recombinant human epidermal growth factor (rhEGF) has emerged as a potential therapeutic agent to enhance wound healing and minimise scar formation. This retrospective study analysed data from March 2020 to June 2023 at a single institution. A total of 105 patients were divided into a control group (n = 70) receiving standard treatment and an observation group (n = 35) receiving standard treatment plus rhEGF. The primary outcomes were the incidence of scar hyperplasia and infection rates, with the secondary outcome being scar aesthetics measured by the visual analogue scale (VAS). No significant differences were found in baseline characteristics between the two groups. The observation group showed a significant reduction in scar hyperplasia (14.3% vs. 57.1%, χ2 = 20.98, p < 0.01) and infection rates (5.7% vs. 21.4%, χ2 = 4.246, p < 0.05) compared to the control group. VAS scores indicated a superior aesthetic outcome in the observation group at all post-treatment timepoints (p < 0.01). rhEGF treatment in oral and maxillofacial trauma patients resulted in favourable healing outcomes and reduced scar formation, improving aesthetic results. These findings highlight the therapeutic potential of rhEGF and underscore the need for larger-scale trials to further investigate its benefits.


Assuntos
Cicatriz , Traumatismos Maxilofaciais , Humanos , Cicatriz/tratamento farmacológico , Hiperplasia/tratamento farmacológico , Estudos Retrospectivos , Proteínas Recombinantes/uso terapêutico , Fator de Crescimento Epidérmico/uso terapêutico , Cicatrização , Traumatismos Maxilofaciais/tratamento farmacológico
2.
Nat Commun ; 15(1): 3302, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658535

RESUMO

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.


Assuntos
Cicatriz , Colágeno , Fibroblastos , Cicatrização , Peixe-Zebra , Humanos , Animais , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Colágeno/metabolismo , Cicatrização/efeitos dos fármacos , Cicatriz/metabolismo , Cicatriz/patologia , Cicatriz/tratamento farmacológico , Pele/metabolismo , Pele/patologia , Pele/efeitos dos fármacos , Fibrose , Peptídeos/farmacologia , Peptídeos/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/patologia , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos
3.
J Cosmet Dermatol ; 23(4): 1113-1121, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38429932

RESUMO

BACKGROUND: Snail mucin is becoming increasingly popular for its wide range of ingredients and potential benefits. Snail extract's widespread appearance in cosmetic formulations encourages an investigation into the medical and cosmetic benefits. AIMS: This study aims to explore current literature on the variety of snail mucin applications. Specifically, we present a review of the uses, global market estimates and projects, and limitations to snail mucin. METHODS: A literature search was conducted on PubMed reviewing snail mucin and their application in medical and dermatologic fields examining their uses. Economic reports were also investigated for Global Market estimates. RESULTS: The therapeutic use of snail mucin in medical fields has been studied as antimicrobial agents, drug delivery vehicles, antitumor agents, wound healing agents, and biomaterial coatings among others. Additionally, the use in cosmetic fields includes antiaging, hydrating, anti-acne, scarring, and hyperpigmentation treatments. It is important to highlight that most studies conducted were preclinical or small clinical studies, stressing the need for additional large-scale clinical trials to support these claims. Investigations into the global market found estimates ranging from $457 million to $1.2 billion with upward projections in the upcoming decade. Limitations include ethical habitats for collection, allergy investigation, and missing clinical studies. CONCLUSIONS: The findings presented here emphasize the expanding uses of snail mucin and its ingredients alongside a growing market cosmetic industry should consider. We also emphasize the need for appropriate clinical trials into the stated benefits of snail mucin to ensure consumer safety and ethical extraction of mucin.


Assuntos
Cosméticos , Mucinas , Pele , Humanos , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Cicatriz/tratamento farmacológico , Cosméticos/química , Mucinas/uso terapêutico , Pele/efeitos dos fármacos , Caramujos/química
4.
J Drugs Dermatol ; 23(3): 146-151, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38443124

RESUMO

BACKGROUND: Topical minoxidil (TM) has been a cornerstone in treating various hair loss disorders, while low-dose oral minoxidil (LDOM) is emerging as an effective alternative. Despite their widespread use, there is a notable gap in the literature regarding their use in treating scarring alopecia. OBJECTIVE: This study evaluates the efficacy and safety of TM and LDOM in managing scarring alopecia. METHODS: A systematic literature search identified relevant studies on TM and LDOM use in central centrifugal cicatricial alopecia, frontal fibrosing alopecia, lichen planopilaris, and traction alopecia. Key metrics included disease stabilization, hair thickness improvement, hair regrowth, and side effect profiles. RESULTS: Analysis of the selected studies revealed mixed outcomes. Most participants experienced benefits in terms of disease stabilization and hair regrowth with TM and LDOM. The majority of cases reported good tolerability of the treatment, although some side effects were noted. CONCLUSION: TM and LDOM show promise in scarring alopecia treatment, demonstrating benefits in disease stabilization and hair regrowth. Despite these positive indications, the variability in results and reported side effects underline the need for further research to establish their consistent efficacy and safety profiles in scarring alopecia treatment. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7743.


Assuntos
Alopecia , Cicatriz , Minoxidil , Humanos , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cabelo , Minoxidil/uso terapêutico
5.
Medicine (Baltimore) ; 103(10): e37062, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457552

RESUMO

BACKGROUND: Endoscopic treatment is increasingly used for refractory gastroesophageal reflux disease (rGERD). Unlike the mechanism of conventional surgical fundoplication, gastroesophageal junction ligation, anti-reflux mucosal intervention, and radiofrequency ablation have extremely similar anti-reflux mechanisms; hence, we collectively refer to them as endoscopic cardia peripheral tissue scar formation (ECSF). We conducted a systematic review and meta-analysis to assess the safety and efficacy of ECSF in treating rGERD. METHODS: We performed a comprehensive search of several databases, including PubMed, Embase, Medline, China Knowledge Network, and Wanfang, to ensure a systematic approach for data collection between January 2011 and July 2023. Forest plots were used to summarize and combine the GERD-health-related quality of life (HRQL), gastroesophageal reflux questionnaire score, and DeMeester scores, acid exposure time, lower esophageal sphincter pressure, esophagitis, proton pump inhibitors use, and patient satisfaction. RESULTS: This study comprised 37 studies, including 1732 patients. After ECSF, significant improvement in gastroesophageal reflux disease health-related quality of life score (mean difference [MD] = 18.27 95% CI: 14.81-21.74), gastroesophageal reflux questionnaire score (MD = 4.85 95% CI: 3.96-5.75), DeMeester score (MD = 42.34, 95% CI: 31.37-53.30), acid exposure time (MD = 7.98, 95% CI: 6.03-9.92), and lower esophageal sphincter pressure was observed (MD = -5.01, 95% CI: -8.39 to 1.62). The incidence of serious adverse effects after ECSF was 1.1% (95% CI: 0.9%-1.2%), and postoperatively, 67.4% (95% CI: 66.4%-68.2%) of patients could discontinue proton pump inhibitor-like drugs, and the treatment outcome was observed to be satisfactory in over 80% of the patients. Subgroup analyses of the various procedures showed that all 3 types improved several objective or subjective patient indicators. CONCLUSIONS: Based on the current meta-analysis, we conclude that rGERD can be safely and effectively treated with ECSF as an endoscopic procedure.


Assuntos
Cárdia , Refluxo Gastroesofágico , Humanos , Qualidade de Vida , Cicatriz/etiologia , Cicatriz/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Endoscopia , Fundoplicatura/métodos , Resultado do Tratamento , Inibidores da Bomba de Prótons/uso terapêutico
6.
Sci Rep ; 14(1): 2821, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308093

RESUMO

Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (p = 0.0016) and 3 to 14 days (p < 0.0001) while dexamethasone-PCL ETT placement resulted in stiffness decreasing from 7 to 14 days (p = 0.031). In the injured airway, localized stiffness at 14 days was significantly greater after regular ETT placement (23.1 ± 0.725 N/m) versus dexamethasone-PCL ETTs (17.10 ± 0.930 N/m, p < 0.0001). Dexamethasone-loaded ETTs were found to reduce laryngotracheal tissue stiffening after simulated intubation injury compared to regular ETTs, supported by a trend of reduced collagen in the basement membrane in injured swine over time. Findings suggest localized corticosteroid delivery allows for tissue stiffness control and potential use as an approach for prevention and treatment of scarring caused by intubation injury.


Assuntos
Cicatriz , Intubação Intratraqueal , Animais , Suínos , Cicatriz/tratamento farmacológico , Traqueia , Corticosteroides , Dexametasona/farmacologia
7.
Dermatology ; 240(2): 195-204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38163426

RESUMO

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.


Assuntos
Dispareunia , Líquen Escleroso Vulvar , Feminino , Humanos , Líquen Escleroso Vulvar/tratamento farmacológico , Líquen Escleroso Vulvar/induzido quimicamente , Líquen Escleroso Vulvar/diagnóstico , Estudos de Coortes , Cicatriz/tratamento farmacológico , Estudos Retrospectivos , Esclerose/induzido quimicamente , Esclerose/tratamento farmacológico , Dispareunia/etiologia , Dispareunia/induzido quimicamente , Resultado do Tratamento , Glucocorticoides/uso terapêutico , Atrofia/tratamento farmacológico , Atrofia/induzido quimicamente
9.
Sci Rep ; 14(1): 1784, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245620

RESUMO

To investigate the risk factors for new renal scarring (NRS) in children with vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). This was a single-center cohort study. The clinical data of 140 children with grade I-V VUR receiving CAP were analyzed. In this study, exposure variables were sex, younger age at the initial diagnosis of UTI ≤ 12 months, the occurrence of breakthrough urinary tract infection (BT-UTI), high-grade VUR, bilateral VUR, etiology, presence of renal scarring at the initial diagnosis and ultrasound abnormalities. The outcome was NRS. A total of 140 children were included in the risk factor analysis of NRS, 73 of whom experienced NRS, an incidence rate of 52.14%. Multivariate Cox regression suggested that the presence of renal function impairment after the initial diagnosis of UTI (OR 3.411, 95% CI 1.5751-6.646) and the occurrence of BT-UTI while receiving CAP (OR 1.995, 95% CI 1.089-2.958) were independent risk factors for NRS. Multivariate Cox regression showed that high-grade VUR had no significant effects on NRS (OR 0.940, 95% CI 0.462-1.912, P = 0.864). No significant difference was identified in multivariate Cox regression analysis in the IV-V group (vs I-III group) (OR 0.960, 95% CI 0.565-1.633, P = 0.960). Renal function impairment after the initial diagnosis of UTI and the occurrence of BT-UTI while receiving CAP were independent risk factors for NRS. Neither univariate analysis nor multivariate analysis found a correlation between VUR grade and NRS.


Assuntos
Infecções Urinárias , Refluxo Vesicoureteral , Criança , Humanos , Lactente , Refluxo Vesicoureteral/complicações , Antibioticoprofilaxia/efeitos adversos , Estudos de Coortes , Cicatriz/tratamento farmacológico , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Infecções Urinárias/tratamento farmacológico , Fatores de Risco , Estudos Retrospectivos
10.
Sci Rep ; 14(1): 1871, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253821

RESUMO

Better agents are needed to improve glaucoma filtration surgery outcomes compared to current ones. The purpose of this study is to determine whether mitogen-activated protein kinase kinase (MEK) inhibitors can effectively arrest the cell cycle of human conjunctival fibroblasts (HCFs) and inhibit the formation of fibrosis and scarring following glaucoma filtration surgery. A cell counting kit­8 assay revealed that the MEK inhibitor PD0325901 exhibited concentration-dependent growth inhibition of HCFs. Quantitative PCR, immunocytochemistry, and western blotting demonstrated decreased expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and increased expression of p27 in HCFs treated with PD0325901. Flow cytometry indicated that PD0325901 arrested the cell cycle of HCFs in the G0/1 phase. The cell-migration assay showed that HCF migration rate was significantly suppressed by PD0325901 exposure. Rabbits were divided into PD0325901-treatment and control groups, and glaucoma filtration surgery was performed. Although intraocular pressure did not differ between PD0325901-treatment and control groups, bleb height was greater in the treatment group. Histopathological evaluation revealed that fibrotic changes were significantly attenuated in the PD0325901-treatment group compared to the control group. In conclusion, the MEK inhibitor impedes HCF proliferation via cell-cycle arrest and may be beneficial for glaucoma filtration surgery by reducing bleb scarring.


Assuntos
Benzamidas , Difenilamina/análogos & derivados , Cirurgia Filtrante , Glaucoma , Animais , Humanos , Coelhos , Cicatriz/tratamento farmacológico , Cicatriz/prevenção & controle , Ciclo Celular , Glaucoma/cirurgia , Inibidores de Proteínas Quinases/farmacologia
11.
Skin Res Technol ; 30(1): e13541, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38174839

RESUMO

INTRODUCTION: Acne vulgaris is a common skin condition that affects a significant percentage of adolescents, with scarring being one of its permanent complications. This study aims to compare the efficacy and safety of using botulinum toxin type A (BTA) in combination with cross-linked and non-cross-linked hyaluronic acid (HA) for the treatment of atrophic acne scars. METHOD: Our study is a randomized, double-blind clinical trial conducted on 16 patients with atrophic acne scars. The patients were randomly assigned to one of two groups: one group received a single session of BTA and crossed link HA combination, while the other group received two sessions of BTA and non-crossed link HA, 1 month apart. The patients were followed up at 3 and 6 months after baseline to evaluate the number and area of fine and large pores and spots, scar grading, patient satisfaction, and complications. RESULTS: The mean age of individuals in both the cross-linked HA and non-cross-linked HA groups was 32.75 ± 4.26 and 31.50 ± 8.48 years, respectively (p = 0.71). In terms of gender, three (37.5%) and seven (87.5%) individuals in the cross-linked and non-cross-linked HA groups were female, respectively (p = 0.11). There were no significant differences in the count and area of fine and large pores and spots between the two groups at baseline and the first follow-up session. However, in the second follow-up session, the non-cross-linked HA group had significantly better results than the cross-linked HA group in terms of large pores count and area (p = 0.01). In terms of changes over time, the non-cross-linked HA group showed significantly better improvements in the count and area of large pores compared to the cross-linked HA group (p = 0.03). Additionally, both groups experienced a significant decrease in the count and area of fine pores over time (p = 0.001), but the amount of changes was not statistically significant between the two groups (p = 0.06). Concerning acne grade, initially, 62.5% and 12.5% of cases in the cross-linked HA and non-cross-linked HA groups, respectively, had severe grades. However, in the last session, these percentages significantly decreased to 0% for both groups (p = 0.002 and 0.005, respectively). In terms of treatment complications, none of the patients experienced any adverse effects. CONCLUSION: The study demonstrated that both cross-linked HA and non-cross-linked HA were effective in reducing acne severity and improving the appearance of pores and spots. The treatments had similar effects on fine pores, spots, and overall acne severity. However, non-cross-linked HA appeared to have a better result on large pores compared to cross-linked HA.


Assuntos
Acne Vulgar , Toxinas Botulínicas Tipo A , Ácido Hialurônico , Adulto , Feminino , Humanos , Masculino , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Atrofia/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cicatriz/patologia , Ácido Hialurônico/uso terapêutico , Satisfação do Paciente , Resultado do Tratamento
12.
Int Wound J ; 21(1): e14649, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38272796

RESUMO

Facial soft tissue injuries, often resulting in scarring, pose a challenge in reconstructive and aesthetic surgery due to the need for functional and aesthetic restoration. This study evaluates the efficacy of recombinant human growth factors (rhGFs) in scar remodelling for such injuries. A retrospective evaluation was conducted from January 2020 to January 2023, involving 100 patients with facial soft tissue injuries. Participants were divided equally into a control group, receiving standard cosmetic surgical repair, and an observation group, treated with rhGFs supplemented cosmetic surgery. The study assessed scar characteristics (pigmentation, pliability, vascularity, height), hospital stay duration, tissue healing time, complication rates and patient satisfaction. The observation group demonstrated significant improvements in all scar characteristics, with notably better pigmentation, pliability, vascularity and height compared with the control group. The rhGF treatment also resulted in reduced hospital stay duration and faster tissue healing. Notably, the total complication rate was significantly lower in the observation group (10%) compared with the control group (34%). Additionally, patient satisfaction levels were higher in the observation group, with 98% combined satisfaction compared with 76% in the control group. The application of rhGFs in treating facial soft tissue injuries significantly enhances scar remodelling, expedites healing, reduces complications and improves patient satisfaction. These findings establish rhGFs as a valuable tool in the management of facial soft tissue injuries, highlighting their potential in improving both functional and aesthetic outcomes.


Assuntos
Traumatismos Faciais , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Humanos , Cicatriz/tratamento farmacológico , Cicatriz/cirurgia , Estudos Retrospectivos , Cicatrização , Lesões dos Tecidos Moles/tratamento farmacológico , Lesões dos Tecidos Moles/cirurgia , Traumatismos Faciais/tratamento farmacológico , Traumatismos Faciais/cirurgia , Resultado do Tratamento
13.
J Cosmet Dermatol ; 23(1): 62-67, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37605366

RESUMO

BACKGROUND: Each year, over 100 million patients are afflicted with new scars from medical procedures worldwide. Natural compounds have shown promise in the treatment of scars and skin disorders. Rosehip oil (RO), produced from the pressed fruit of the rosehip (Rosa canina L.) plant, is used in the pharmaceutical, cosmetic, and food industries. The use of this plant in the treatment of scars has yet to be reviewed. AIMS: This review aims to analyze the current findings on the use of RO in the treatment of postsurgical scars. METHODS: This literature search considered published journal articles (clinical trials or literature reviews). Studies were identified by searching electronic databases (PubMed and MEDLINE) and reference lists of respective articles. Additional articles were identified through Google Scholar. Only articles available in English were included in this review. RESULTS: There is a scarcity of high-quality studies assessing the therapeutic potential of RO. From the two human clinical trials using RO, there is some evidence to suggest its potential as an active ingredient in topical formulations for the treatment of wounds. Topical treatments containing RO extract may reduce the size and erythema of postsurgical scars through the polarization of macrophages and the inhibition of inflammatory cytokines. CONCLUSIONS: Some evidence suggests that RO may improve postsurgical scars. At present, there is insufficient evidence to recommend the use of RO for the treatment of wounds. Further investigation is required to establish its therapeutic effects on human skin and its potential use as an ingredient in topical formulations.


Assuntos
Cicatriz , Rosa , Humanos , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cicatrização
14.
Cancer Treat Res ; 186: 43-70, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37978130

RESUMO

Identification of tumours that have homologous recombination deficiency (HRD) has become of increasing interest following the licensing of PARP inhibitors. Potential methods to assess HRD status include; clinical selection for platinum sensitive disease, mutational/methylation status, genomic scars/signature and functional RAD51 assays. Homologous recombination (HR) is a dynamic process with the potential to evolve over a disease course, particularly in relation to previous treatment. This is one of the major drawbacks of genomic scars/signatures, as they only demonstrate historic HR status. Functional HR assays have the benefit of giving a real time HR status readout and therefore have the potential for clearer identification of patients who may benefit from PARP inhibitors at that specific time point. However, the development of RAD51 foci assays ready for clinical practice has been challenging. Pre-clinical considerations have included; controlling for variation in tumour proliferation, tissue type and whether DNA damage induction is required. Furthermore, the assays require correlation with clinical outcomes, an understanding of how they complement current testing modalities and validation of test performance in large cohorts. Despite these challenges, given the profound benefit from PARP inhibitors seen in those with an HRD phenotype to date, the ongoing development and validation of these functional HR assays remains of high clinical importance.


Assuntos
Neoplasias , Neoplasias Ovarianas , Humanos , Feminino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Cicatriz/tratamento farmacológico , Cicatriz/patologia , Recombinação Homóloga , Neoplasias/tratamento farmacológico , Neoplasias/genética , Dano ao DNA
15.
Medicina (Kaunas) ; 59(10)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37893592

RESUMO

Background and Objectives: Good scar management in burn care is essential. Nevertheless, there are no consistent recommendations regarding moisturizers for scar management. Our aim was to investigate and compare the effects of commonly used products on normal skin and burn scars. Materials and Methods: A total of 30 skin-healthy (control group) and 12 patients with burn scars were included in this study. For an intraindividual comparison, each participant received creams consisting of dexpanthenol (P), aloe vera (A), and a natural plant oil (O) with instructions to apply them daily to a previously defined area for at least 28 days. Objective scar evaluation was performed with Visioscan®; Tewameter®; Cutometer®, and the Oxygen To See® device. Subjective evaluation was performed with an "application" questionnaire, the Patient and Observer Scar Assessment Scale (POSAS), and with the "best of three" questionnaire. Results: After (A) a high trend of amelioration of +30%, TEWL was detected on the scar area. Blood flow increased slightly on healthy skin areas after (A) application to +104%. The application of (A) on healthy skin demonstrated a positive effect on the parameters of scaliness (+22%, p < 0.001), softness (+14%, p = 0.046), roughness R1 (+16%, p < 0.001) and R2 (+17%, p = 0.000), volume (+22%, p < 0.001), and surface area (+7%, p < 0.001) within the control group. After (P), a significant improvement of the baseline firmness parameter of +14.7% was detected (p = 0.007). (P) also showed a beneficial effect on the parameters of R1 (+7%, p = 0.003), R2 (+6%, p = 0.001), and volume (+17%, p = 0.001). (O) lead to a statistically significant improvement of volume (+15%, p = 0.009). Overall, most study participants stated (A) to be the "best of three". Conclusions: (A) performed statistically best, and is a well-tolerated moisturizing product. However, further quantitative studies are needed to provide statistically significant clarification for uniform recommendations for scar therapy.


Assuntos
Aloe , Queimaduras , Humanos , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Pele/patologia
16.
Biomed Pharmacother ; 168: 115710, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37862963

RESUMO

Spinal cord injury (SCI) is a devastating event that often results in the inflammatory condition of glial scar tissue formation, impeding neural regeneration and recovery. Reducing the inflammatory response and inhibiting glial formation are promising strategies for improving SCI outcomes. Here, we introduce a new role for Shinbaro2 (Sh2), known for its anti-inflammatory and pain-reducing effects, in ameliorating glial scars formed in the damaged spinal cord and promoting axon growth after SCI. Sh2 was applied at various concentrations to cultivate primary spinal cord neurons. Concentrations of 1 and 2 mg/mL effectively enhanced cell viability and axonal outgrowth in spinal cord neurons subjected to hydrogen peroxide or laceration injury. Sh2 helped reduce neuroinflammation by increasing anti-inflammatory M2 macrophages (arginase 1) and decreasing inflammatory cells, ultimately reducing lesion size. In scar formation, Sh2 inhibited the expression of ß-catenin and nestin in reactive astrocytes in the injured spinal cord. Moreover, Sh2 suppressed the expression of chondroitin sulfate proteoglycans and SOX9, which are involved in scar formation. Furthermore, Sh2 promoted the sprouting of serotonergic axons and the growth of neurofibrillary tangles, enhancing motor function recovery in SCI. These findings highlight the potential of Sh2 as an SCI therapeutic intervention, offering hope for neural and functional restoration in individuals with this debilitating condition.


Assuntos
Gliose , Traumatismos da Medula Espinal , Ratos , Animais , Gliose/patologia , Cicatriz/tratamento farmacológico , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/tratamento farmacológico , Axônios , Medula Espinal/metabolismo , Anti-Inflamatórios/farmacologia
17.
J Plast Reconstr Aesthet Surg ; 87: 10-16, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37804642

RESUMO

BACKGROUND: Although different options are available for treating post-traumatic facial scars, they remain a therapeutic challenge. AIM: To evaluate the safety and effectiveness of combined therapy using micro-plasma radiofrequency (MPRF) technology and silicone gel (SG) dressings for treating post-traumatic facial scars. METHODS: This retrospective study was conducted at a single center. Patients with facial injuries in the outpatient and emergency units of the Department of Plastic Surgery at our hospital underwent debridement and cosmetic sutures performed by the same surgeon from October 2020 to October 2021. In the first arm, patients with facial injuries were treated with MPRF technology and SG, and in the second arm, they were treated with SG dressings alone. We observed the safety and effectiveness of these treatments in both arms. RESULTS: A total of 32 patients with facial injuries were treated with MPRF technology and SG dressings (combined treatment group), and 28 patients were treated with SG dressings alone (SG group). After 6 months of treatment, the Vancouver Scar Scale scores of the combined treatment and SG groups were 1.38 ± 0.71 and 4.39 ± 0.50, respectively, and the difference was statistically significant (P < 0.01). After 6 months of treatment, the effectiveness rate in the combined treatment group was 93.8%, which was significantly higher than that in the SG group (67.9%), and the difference between the two groups was statistically significant (P < 0.05). No obvious adverse reactions occurred in the two arms. CONCLUSION: Treating early post-traumatic facial scars with combined MPRF technology and SG is significantly better than treating them with SG alone; moreover, the combined therapy is safe and effective.


Assuntos
Cicatriz Hipertrófica , Traumatismos Faciais , Humanos , Cicatriz/terapia , Cicatriz/tratamento farmacológico , Estudos Retrospectivos , Géis de Silicone/uso terapêutico , Bandagens , Traumatismos Faciais/complicações , Traumatismos Faciais/terapia , Resultado do Tratamento , Cicatriz Hipertrófica/terapia
18.
J Dermatol ; 50(12): 1513-1522, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37665181

RESUMO

Maintenance therapy after remission of inflammation is strongly recommended in the guideline for the treatment of acne vulgaris published by the Japanese Dermatological Association. One advantage of continuing maintenance therapy is the alleviation of atrophic scarring. This study investigated the efficacy of maintenance therapy using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel, and its effects on atrophic scarring. Overall, 126 patients were randomized to the adapalene/benzoyl peroxide group (n = 40), benzoyl peroxide group (n = 44), and control group (without maintenance treatment drugs; n = 42), and 111 of these completed a trial lasting 24 weeks. As the primary endpoint, the treatment success rate (the percentage of patients in whom the number of inflammatory lesions was maintained at ≤10) was 89.2% in the adapalene/benzoyl peroxide group, 87.5% in the benzoyl peroxide group, and 47.4% in the control group. Compared with the control group, the success rates were significantly higher in the adapalene/benzoyl peroxide and benzoyl peroxide groups (P = 0.0006 for both). As one of the secondary endpoints, the rate of change in the number of atrophic scars showed significant improvement from the baseline in the adapalene/benzoyl peroxide and benzoyl peroxide groups at week 24 (P = 0.0004 and P < 0.0001, respectively). Although the three-dimensional image analysis parameters did not change significantly from the baseline in the adapalene/benzoyl peroxide and benzoyl peroxide groups at week 24, significant worsening was noted in the control group (P = 0.0276 for affected area, P = 0.0445 for volume, and P = 0.0182 for maximum depth). Adverse drug reactions were noted in three patients in the adapalene/benzoyl peroxide group (7.5%) but not in the benzoyl peroxide group. These findings suggest that maintenance therapy using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel is effective in preventing the worsening of scars in Japanese patients with acne vulgaris.


Assuntos
Acne Vulgar , Combinação Adapaleno e Peróxido de Benzoil , Doenças do Tecido Conjuntivo , Fármacos Dermatológicos , Humanos , Adapaleno/uso terapêutico , Peróxido de Benzoíla/uso terapêutico , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cicatriz/patologia , Fármacos Dermatológicos/uso terapêutico , Imageamento Tridimensional , Administração Cutânea , Géis/uso terapêutico , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Acne Vulgar/induzido quimicamente , Combinação Adapaleno e Peróxido de Benzoil/efeitos adversos , Resultado do Tratamento , Doenças do Tecido Conjuntivo/induzido quimicamente , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/tratamento farmacológico , Atrofia/induzido quimicamente , Combinação de Medicamentos
19.
J Ocul Pharmacol Ther ; 39(10): 716-724, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37669059

RESUMO

Purpose: To evaluate the effects of bevacizumab in 3 different application methods, subconjunctival injection (SCI), hyaluronic acid retardant (HAR), and eye drop (ED), on attenuating scar formation in the filtering bleb. Methods: Trabeculectomy (TRAB) was performed on New Zealand rabbits. TRAB rabbits were intervened with bevacizumab SCI, HAR, ED, or mitomycin C, respectively. Intraocular pressure (IOP) of 1, 7, 14, and 28 days after TRAB was recorded, and the bleb survival rate was analyzed. Bleb height, area, and vascularization were evaluated using anterior segment optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) at 7, 14 and 28 days after surgery. A histopathology examination of the bleb tissue was performed. The expression levels of vascular endothelial growth factor (VEGF)-A, interleukin (IL)-1α, tumor necrosis factor-alpha (TNF-α), transforming growth factor-ß1 (TGF-ß1), and α-smooth muscle actin (α-SMA) were measured by Western blot. Results: Bevacizumab significantly reduced postoperative IOP and increased the survival of the filtering bleb, especially in the ED group. Less vascularization was shown in the SCI, HAR, and ED groups. Histopathological results showed the fewest levels of scarring and fibrosis in the ED group. The local VEGF-A, IL-1α, and TNF-α expression levels after bevacizumab ED were decreased, combined with suppression of TGF-ß1 and α-SMA. Conclusions: Postoperative use of bevacizumab EDs was an effective application method for improving surgical outcomes after TRAB in rabbits. It might be effective in preventing scarring of the filtering bleb by antivascularization and anti-inflammation.


Assuntos
Glaucoma , Trabeculectomia , Coelhos , Animais , Trabeculectomia/métodos , Bevacizumab/farmacologia , Glaucoma/tratamento farmacológico , Glaucoma/cirurgia , Glaucoma/patologia , Fator A de Crescimento do Endotélio Vascular , Fator de Crescimento Transformador beta1 , Cicatriz/tratamento farmacológico , Cicatriz/prevenção & controle , Cicatriz/patologia , Fator de Necrose Tumoral alfa , Pressão Intraocular , Túnica Conjuntiva , Administração Tópica
20.
Acta Biomater ; 171: 289-307, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37683964

RESUMO

Corneal scarring and opacification are a significant cause of blindness affecting millions worldwide. The current standard of care for corneal blindness is corneal transplantation, which suffers from several drawbacks. One alternative approach that has shown promise is the use of xenogeneic corneal extracellular matrix (ECM), but its clinical applicability is challenging due to safety concerns. This study reports the innovative use of human cornea-derived ECM to prevent post-traumatic corneal scarring. About 30 - 40% of corneas donated to the eye banks do not meet the standards defined for clinical use and are generally discarded, although they are completely screened for their safety. In this study, human cornea-derived decellularized ECM hydrogel was prepared from the non-transplantation grade human cadaveric corneas obtained from an accredited eye-bank. The prepared hydrogel was screened for its efficacy against corneal opacification following an injury in an animal model. Our in vivo study revealed that, the control collagen-treated group developed corneal opacification, while the prophylactic application of human cornea-derived hydrogel effectively prevented corneal scarring and opacification. The human hydrogel-treated corneas were indistinguishable from healthy corneas and comparable to those treated with the xenogeneic bovine corneal hydrogel. We also demonstrated that the application of the hydrogel retained the biological milieu including cell behavior, protein components, optical properties, curvature, and nerve regeneration by remodeling the corneal wound after injury. The hydrogel application is also sutureless, resulting in faster corneal healing. We envision that this human cornea-derived ECM-based hydrogel has potential clinical application in preventing scarring from corneal wounding. STATEMENT OF SIGNIFICANCE: There are significant challenges surrounding corneal regeneration after injury due to extensive scarring. Although there is substantial research on corneal regeneration, much of it uses synthetic materials with chemical cross-linking methods or xenogeneic tissue-based material devices which have to undergo exhaustive safety analysis before clinical trials. Herein, we demonstrate the potential application of a human corneal extracellular matrix hydrogel without any additional materials for scarless corneal tissue regeneration, and a method to reduce the wasting of donated allogenic corneal tissue from eye banks. We found no difference in efficacy between the usage of human tissues compared to xenogeneic sources. This may help ease clinical translation and can be used topically without sutures as an outpatient procedure.


Assuntos
Cicatriz , Lesões da Córnea , Humanos , Animais , Bovinos , Cicatriz/prevenção & controle , Cicatriz/tratamento farmacológico , Hidrogéis/farmacologia , Hidrogéis/química , Córnea/cirurgia , Matriz Extracelular/química , Cegueira
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