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1.
J Drugs Dermatol ; 23(5): e132-e133, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709690

RESUMO

Skin self-examinations play a vital role in skin cancer detection and are often aided by online resources. Available reference photos must display the full spectrum of skin tones so patients may visualize how skin lesions can appear. This study investigated the portrayal of skin tones in skin cancer-related Google Images, discovering a significant underrepresentation of darker skin tones. J Drugs Dermatol. 2024;23(5):e132-e133.     doi:10.36849/JDD.7886e.


Assuntos
Neoplasias Cutâneas , Pigmentação da Pele , Humanos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Fotografação , Autoexame/métodos , Pele/patologia , Internet , Ferramenta de Busca
2.
Sci Rep ; 14(1): 10524, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719976

RESUMO

Extracellular matrix diseases like fibrosis are elusive to diagnose early on, to avoid complete loss of organ function or even cancer progression, making early diagnosis crucial. Imaging the matrix densities of proteins like collagen in fixed tissue sections with suitable stains and labels is a standard for diagnosis and staging. However, fine changes in matrix density are difficult to realize by conventional histological staining and microscopy as the matrix fibrils are finer than the resolving capacity of these microscopes. The dyes further blur the outline of the matrix and add a background that bottlenecks high-precision early diagnosis of matrix diseases. Here we demonstrate the multiple signal classification method-MUSICAL-otherwise a computational super-resolution microscopy technique to precisely estimate matrix density in fixed tissue sections using fibril autofluorescence with image stacks acquired on a conventional epifluorescence microscope. We validated the diagnostic and staging performance of the method in extracted collagen fibrils, mouse skin during repair, and pre-cancers in human oral mucosa. The method enables early high-precision label-free diagnosis of matrix-associated fibrotic diseases without needing additional infrastructure or rigorous clinical training.


Assuntos
Microscopia de Fluorescência , Animais , Camundongos , Humanos , Microscopia de Fluorescência/métodos , Proteínas da Matriz Extracelular/metabolismo , Imagem Óptica/métodos , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Pele/metabolismo , Pele/patologia
3.
Skin Res Technol ; 30(5): e13706, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38721854

RESUMO

BACKGROUND: The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time-consuming. We describe the development of a novel approach to high-throughput sampling of tissue lipids using electroporation-based biopsy, termed e-biopsy. We report on the ability of the e-biopsy technique to harvest large amounts of lipids from human skin samples. MATERIALS AND METHODS: Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) providing cSCC, BCC, and healthy skin lipidomic profiles. RESULTS: Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso-phospholipids in cSCC compared to healthy skin tissue samples. CONCLUSION: The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e-biopsy technique for the analysis of lipidomic profiles of human skin tissues.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Eletroporação , Lipidômica , Neoplasias Cutâneas , Pele , Humanos , Carcinoma Basocelular/patologia , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/química , Lipidômica/métodos , Biópsia , Pele/patologia , Pele/metabolismo , Pele/química , Feminino , Masculino , Eletroporação/métodos , Pessoa de Meia-Idade , Idoso , Lipídeos/análise , Espectrometria de Massas em Tandem/métodos
4.
Int J Mol Sci ; 25(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732058

RESUMO

Monitoring inflammatory cytokines is crucial for assessing healing process and photobiomodulation (PBM) enhances wound healing. Meanwhile, cAMP response element-binding protein (CREB) is a regulator of cellular metabolism and proliferation. This study explored potential links between inflammatory cytokines and the activity of CREB in PBM-treated wounds. A total of 48 seven-week-old male SD rats were divided into four groups (wound location, skin or oral; treatment method, natural healing or PBM treatment). Wounds with a 6 mm diameter round shape were treated five times with an 808 nm laser every other day (total 60 J). The wound area was measured with a caliper and calculated using the elliptical formula. Histological analysis assessed the epidermal regeneration and collagen expression of skin and oral tissue with H&E and Masson's trichrome staining. Pro-inflammatory (TNF-α) and anti-inflammatory (TGF-ß) cytokines were quantified by RT-PCR. The ratio of phosphorylated CREB (p-CREB) to unphosphorylated CREB was identified through Western blot. PBM treatment significantly reduced the size of the wounds on day 3 and day 7, particularly in the skin wound group (p < 0.05 on day 3, p < 0.001 on day 7). The density of collagen expression was significantly higher in the PBM treatment group (in skin wound, p < 0.05 on day 3, p < 0.001 on day 7, and p < 0.05 on day 14; in oral wound, p < 0.01 on day 7). The TGF-ß/TNF-α ratio and the p-CREB/CREB ratio showed a parallel trend during wound healing. Our findings suggested that the CREB has potential as a meaningful marker to track the wound healing process.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Terapia com Luz de Baixa Intensidade , Ratos Sprague-Dawley , Cicatrização , Animais , Cicatrização/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Masculino , Ratos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Pele/metabolismo , Pele/efeitos da radiação , Pele/patologia , Pele/lesões , Citocinas/metabolismo , Fosforilação/efeitos da radiação , Fator de Necrose Tumoral alfa/metabolismo , Colágeno/metabolismo , Fator de Crescimento Transformador beta/metabolismo
5.
Arch Dermatol Res ; 316(5): 156, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734816

RESUMO

Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1ß and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1ß, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1ß expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1ß (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1ß, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1ß, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1ß in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Caspase 1 , Dermatite Atópica , Inflamassomos , Interleucina-18 , Interleucina-1beta , Peptídeos e Proteínas de Sinalização Intracelular , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas de Ligação a Fosfato , Humanos , Inflamassomos/metabolismo , Inflamassomos/imunologia , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Macrófagos/metabolismo , Macrófagos/imunologia , Interleucina-1beta/metabolismo , Masculino , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Adulto , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Caspase 1/metabolismo , Pele/patologia , Pele/imunologia , Pele/metabolismo , Índice de Gravidade de Doença , Pessoa de Meia-Idade , Antígenos de Diferenciação Mielomonocítica/metabolismo , Adulto Jovem , Proteínas Reguladoras de Apoptose/metabolismo , Antígenos CD/metabolismo , Proteínas NLR/metabolismo , Estudos de Casos e Controles , Epiderme/imunologia , Epiderme/metabolismo , Epiderme/patologia , Gasderminas , Molécula CD68 , Proteínas de Ligação a DNA
6.
J Investig Med High Impact Case Rep ; 12: 23247096241253337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742532

RESUMO

Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.


Assuntos
Linfo-Histiocitose Hemofagocítica , Linfoma de Células T , Paniculite , Humanos , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Paniculite/patologia , Paniculite/diagnóstico , Linfoma de Células T/patologia , Linfoma de Células T/complicações , Linfoma de Células T/diagnóstico , Evolução Fatal , Adulto , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/complicações , Pele/patologia , Biópsia , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/complicações , Linfoma Cutâneo de Células T/diagnóstico , Diagnóstico Diferencial
7.
PLoS One ; 19(5): e0302991, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722855

RESUMO

Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene. The Col7a1 gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the Col7a1 gene can cause aberrant collagen type VII formation, causing an associated lack or absence of anchoring fibrils. This presents clinically as chronic blistering, scarring, and fibrosis, often leading to the development of cutaneous squamous cell carcinoma. Patients also experience persistent pain and pruritus. Pain management and supportive bandaging remain the primary treatment options. The pathology of recessive dystrophic epidermolysis bullosa was first described in the 1980s, and there has since been a multitude of encouraging treatment options developed. However, in vivo research has been hindered by inadequate models of the disease. The various mouse models in existence possess longevity and surface area constraints, or do not adequately model a normal human disease state. In this paper, we describe a novel rat model of recessive dystrophic epidermolysis bullosa that offers an alternative to previous murine models. An 8-base pair deletion was induced in the Col7a1 gene of Lewis rats, which was subsequently found to cause a premature stop codon downstream. Homozygous mutants presented with a fragile and chronically blistered phenotype postnatally. Further histological analysis revealed subepidermal clefting and the absence of anchoring fibrils. The generation of this novel model offers researchers an easily maintained organism that possesses a larger surface area for experimental topical and transfused therapies to be tested, which may provide great utility in the future study of this debilitating disease.


Assuntos
Colágeno Tipo VII , Modelos Animais de Doenças , Epidermólise Bolhosa Distrófica , Mutação da Fase de Leitura , Fenótipo , Colágeno Tipo VII/genética , Animais , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Distrófica/patologia , Ratos , Genes Recessivos , Ratos Endogâmicos Lew , Vesícula/genética , Vesícula/patologia , Pele/patologia , Masculino
8.
BMC Immunol ; 25(1): 30, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734636

RESUMO

BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an idiopathic inflammatory myopathy (IIM). Though patients with IMNM were not considered to show skin rash, several reports have showed atypical skin conditions in patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive IMNM (HMGCR-IMNM). The incidence and phenotype of skin conditions in patients with HMGCR-IMNM are not fully known. RESULTS: Among the 100 IIM patients diagnosed from April 2015 through August 2022, 34 (34%) presented some form of skin condition, with 27 having typical skin rashes; this included 13 patients with dermatomyositis (DM), 8 with anti-synthetase syndrome (ASS), and 6 with IMNM. Meanwhile, 8 of 19 patients with HMGCR-IMNM (42%) presented atypical skin lesions, but no patients with other IIMs did (p < 0.001). Skin eruption with ash-like scales was observed in four HMGCR-IMNM patients, and non-scaly red patches and lumps in the other four patients; accordingly, their skin manifestations were considered as other dermal diseases except for IIM. However, skin and muscle biopsies revealed the atypical skin conditions of patients with HMGCR-IMNM to have the same pathological background, formed by Bcl-2-positive lymphocyte infiltrations. CONCLUSIONS: HMGCR-IMNM patients frequently have atypical skin conditions of the neck and back. Skin biopsy specimens from these lesions showed the same Bcl-2-positive lymphocytic infiltrations as muscle biopsy specimens regardless of the different gross dermal findings. Thus, such atypical skin conditions may be suggestive for HMGCR-IMNM.


Assuntos
Autoanticorpos , Hidroximetilglutaril-CoA Redutases , Miosite , Pele , Humanos , Hidroximetilglutaril-CoA Redutases/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Autoanticorpos/imunologia , Autoanticorpos/sangue , Adulto , Pele/patologia , Pele/imunologia , Miosite/imunologia , Miosite/diagnóstico , Idoso , Dermatopatias/imunologia , Dermatopatias/etiologia , Doenças Musculares/imunologia , Doenças Musculares/diagnóstico , Biópsia
9.
Eur J Med Res ; 29(1): 282, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735974

RESUMO

BACKGROUND: Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. METHODS: Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 - (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 - and AST 2 + groups and cutoff value calculations. RESULTS: Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71-0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. CONCLUSIONS: This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.


Assuntos
Neoplasias da Mama , Aprendizado de Máquina , Humanos , Feminino , Neoplasias da Mama/radioterapia , Pessoa de Meia-Idade , Adulto , Idoso , Pele/efeitos da radiação , Pele/patologia , Lesões por Radiação/etiologia , Lesões por Radiação/diagnóstico , Dosagem Radioterapêutica
10.
Front Immunol ; 15: 1383263, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736879

RESUMO

Acne vulgaris is one of the most common skin diseases. The current understanding of acne primarily revolves around inflammatory responses, sebum metabolism disorders, aberrant hormone and receptor expression, colonization by Cutibacterium acnes, and abnormal keratinization of follicular sebaceous glands. Although the precise mechanism of action remains incompletely understood, it is plausible that macrophages exert an influence on these pathological features. Macrophages, as a constituent of the human innate immune system, typically manifest distinct phenotypes across various diseases. It has been observed that the polarization of macrophages toward the M1 phenotype plays a pivotal role in the pathogenesis of acne. In recent years, extensive research on acne has revealed an increasing number of natural remedies exhibiting therapeutic efficacy through the modulation of macrophage polarization. This review investigates the role of cutaneous macrophages, elucidates their potential significance in the pathogenesis of acne, a prevalent chronic inflammatory skin disorder, and explores the therapeutic mechanisms of natural plant products targeting macrophages. Despite these insights, the precise role of macrophages in the pathogenesis of acne remains poorly elucidated. Subsequent investigations in this domain will further illuminate the pathogenesis of acne and potentially offer guidance for identifying novel therapeutic targets for this condition.


Assuntos
Acne Vulgar , Macrófagos , Acne Vulgar/imunologia , Acne Vulgar/tratamento farmacológico , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Produtos Biológicos/uso terapêutico , Produtos Biológicos/farmacologia , Animais , Pele/imunologia , Pele/patologia , Pele/metabolismo
11.
Skin Res Technol ; 30(5): e13727, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38711343

RESUMO

Wound healing is a complex, intricate, and dynamic process that requires effective therapeutic management. The current study evaluates the wound healing potentials of methanolic extract of Cuminum cyminum L. seeds (CCS) in rats. Sprague Dawley (24) rats were distributed into four cages, wounds produced on the back of the neck, and received two daily topical treatments for 14 days: A, rats received normal saline; B, wounded rats treated with intrasite gel; C and D, rats received 0.2 mL of 250 and 500 mg/kg of CCS, respectively. After that, wound area and closure percentage were evaluated, and wound tissues were dissected for histopathological, immunohistochemical, and biochemical examinations. Acute toxicity trials of methanolic extract of CCS showed the absence of any physiological changes or mortality in rats. CCS application caused a significant reduction in wound size and a statistically elevated percentage of wound contraction than those of vehicle rats. CCS treatment caused significant up-regulation of collagen fiber, fibroblasts, and fewer inflammatory cells (inflammation) in granulation tissues. TGF-ß1 (angiogenetic factor) was significantly more expressed in CCS-treated rats in comparison to normal saline-treated rats; therefore, more fibroblasts transformed into myofibroblasts (angiogenesis). CCS-treated rats showed remarkable antioxidant potentials (higher SOD and CAT enzymes) and decreased MDA (lipid peroxidation) levels in their wound tissue homogenates. Hydroxyproline amino acid (collagen) was significantly up-regulated by CCS treatment, which is commonly related to faster wound closure area. The outcomes suggest CCS as a viable new source of pharmaceuticals for wound treatment.


Assuntos
Cuminum , Extratos Vegetais , Ratos Sprague-Dawley , Sementes , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Sementes/química , Ratos , Extratos Vegetais/farmacologia , Cuminum/química , Masculino , Pele/lesões , Pele/efeitos dos fármacos , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo
12.
J Drugs Dermatol ; 23(5): 360-365, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709707

RESUMO

BACKGROUND: The use of ointments can be beneficial for dry, chapped, or cracked skin and also for supporting wound healing. We describe the results of 2 studies with an over-the-counter healing ointment (HO) to evaluate the effects on skin hydration and in the setting of wound healing after dermatologic procedures.  Methods: Study 1 was a single-center, in-use study using HO on qualified areas at least once daily for 4 weeks in subjects with dry, cracked body skin and self-perceived sensitive skin. Study 2 was a multi-center study of wound healing in subjects using HO on a daily basis after having dermatologic surgical procedures.  Results: In Study 1, there was a significant reduction in skin dryness after 1 and 4 weeks of HO use (P<0.05). Image analysis of the skin revealed a significant increase in skin smoothness after the first application of HO in 100% of subjects (P<0.05). Tolerability and safety were excellent, and HO was well-perceived by subjects throughout the study. In Study 2, HO improved clinical assessments at all time points compared with baseline with a decrease in erythema, edema, scabbing/crusting, and an improvement in overall wound appearance (P<0.05). There was no worsening or significant increase in measures for tolerability parameters at any study visits. Additionally, HO achieved a favorable perception by study subjects.  Conclusions: HO has a well-established safety profile and has been shown to improve both skin hydration and the overall wound healing process after dermatologic surgical procedures. J Drugs Dermatol. 2024;23(5):360-365. doi:10.36849/JDD.8224.


Assuntos
Medicamentos sem Prescrição , Pomadas , Cicatrização , Humanos , Cicatrização/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Medicamentos sem Prescrição/administração & dosagem , Idoso , Resultado do Tratamento , Dermatopatias/tratamento farmacológico , Pele/efeitos dos fármacos , Pele/patologia , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Adulto Jovem , Administração Cutânea
13.
Am J Reprod Immunol ; 91(5): e13853, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38706383

RESUMO

BACKGROUND: The amniotic membrane (AM) has shown immense potential in repairing wounds due to its great regenerative qualities. Although the role of AM as a biological scaffold in repairing wounds has been studied well, the tissue regenerative potential of AM-derived mesenchymal stem cells (MSCs) and conditioned media (CM) derived from it remains to be discovered as of now. Here, we examined the wound healing abilities of fresh and frozen thawed rabbit AM (rAM) along with the MSCs and their lyophilised CM in rabbits challenged with skin wounds. METHODS: To elucidate the role of rAM-MSCs and its CM in repairing the wound, we isolated it from the freshly derived placenta and characterised their differentiation potential by performing an in vitro tri-lineage differentiation assay besides other standard confirmations. We compared the wound repair capacities of rAM-MSCs and lyophilised CM with the fresh and cryopreserved AM at different timelines by applying them to excision wounds created in rabbits. RESULTS: By monitoring wound contractions and tissue histology of wounded skin at different time points after the application, we observed that rAM-MSCs and rAM-MSC-derived CM significantly promoted wound closure compared to the control group. We also observed that the wound closure capacity of rAM-MSCs and rAM-MSC-derived CM is as efficient as fresh and cryopreserved rAM. CONCLUSION: Our findings suggest that rAM-MSCs and rAM-MSC derived CM can be effectively used to treat skin wounds in animals and correctly delivered to the damaged tissue using AM as a bioscaffold, either fresh or frozen.


Assuntos
Âmnio , Células-Tronco Mesenquimais , Cicatrização , Animais , Coelhos , Feminino , Células-Tronco Mesenquimais/citologia , Diferenciação Celular , Meios de Cultivo Condicionados/farmacologia , Transplante de Células-Tronco Mesenquimais/métodos , Pele/lesões , Pele/patologia , Gravidez , Modelos Animais de Doenças , Células Cultivadas , Transplante Homólogo
14.
J Transl Med ; 22(1): 449, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741129

RESUMO

Inherited deficiency of thymidine phosphorylase (TP), encoded by TYMP, leads to a rare disease with multiple mitochondrial DNA (mtDNA) abnormalities, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). However, the impact of TP deficiency on lysosomes remains unclear, which are important for mitochondrial quality control and nucleic acid metabolism. Muscle biopsy tissue and skin fibroblasts from MNGIE patients, patients with m.3243 A > G mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and healthy controls (HC) were collected to perform mitochondrial and lysosomal functional analyses. In addition to mtDNA abnormalities, compared to controls distinctively reduced expression of LAMP1 and increased mitochondrial content were detected in the muscle tissue of MNGIE patients. Skin fibroblasts from MNGIE patients showed decreased expression of LAMP2, lowered lysosomal acidity, reduced enzyme activity and impaired protein degradation ability. TYMP knockout or TP inhibition in cells can also induce the similar lysosomal dysfunction. Using lysosome immunoprecipitation (Lyso- IP), increased mitochondrial proteins, decreased vesicular proteins and V-ATPase enzymes, and accumulation of various nucleosides were detected in lysosomes with TP deficiency. Treatment of cells with high concentrations of dThd and dUrd also triggers lysosomal dysfunction and disruption of mitochondrial homeostasis. Therefore, the results provided evidence that TP deficiency leads to nucleoside accumulation in lysosomes and lysosomal dysfunction, revealing the widespread disruption of organelles underlying MNGIE.


Assuntos
DNA Mitocondrial , Fibroblastos , Lisossomos , Mitocôndrias , Encefalomiopatias Mitocondriais , Nucleosídeos , Timidina Fosforilase , Humanos , Lisossomos/metabolismo , Timidina Fosforilase/metabolismo , Timidina Fosforilase/deficiência , Timidina Fosforilase/genética , Encefalomiopatias Mitocondriais/metabolismo , Encefalomiopatias Mitocondriais/patologia , Encefalomiopatias Mitocondriais/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Nucleosídeos/metabolismo , Pseudo-Obstrução Intestinal/metabolismo , Pseudo-Obstrução Intestinal/patologia , Pseudo-Obstrução Intestinal/enzimologia , Pseudo-Obstrução Intestinal/genética , Oftalmoplegia/metabolismo , Oftalmoplegia/patologia , Oftalmoplegia/congênito , Distrofia Muscular Oculofaríngea/metabolismo , Distrofia Muscular Oculofaríngea/patologia , Masculino , Feminino , Pele/patologia , Pele/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo
15.
ACS Nano ; 18(19): 12341-12354, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38695772

RESUMO

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.


Assuntos
Nanofibras , Animais , Ratos , Nanofibras/química , Cicatrização/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Aderências Teciduais/prevenção & controle , Ratos Sprague-Dawley , Adesão Celular/efeitos dos fármacos , Cério/química , Cério/farmacologia , Propriedades de Superfície , Camundongos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
16.
Comput Biol Med ; 175: 108549, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704901

RESUMO

In this paper, we propose a multi-task learning (MTL) network based on the label-level fusion of metadata and hand-crafted features by unsupervised clustering to generate new clustering labels as an optimization goal. We propose a MTL module (MTLM) that incorporates an attention mechanism to enable the model to learn more integrated, variable information. We propose a dynamic strategy to adjust the loss weights of different tasks, and trade off the contributions of multiple branches. Instead of feature-level fusion, we propose label-level fusion and combine the results of our proposed MTLM with the results of the image classification network to achieve better lesion prediction on multiple dermatological datasets. We verify the effectiveness of the proposed model by quantitative and qualitative measures. The MTL network using multi-modal clues and label-level fusion can yield the significant performance improvement for skin lesion classification.


Assuntos
Pele , Humanos , Pele/diagnóstico por imagem , Pele/patologia , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Redes Neurais de Computação , Algoritmos , Dermatopatias/diagnóstico por imagem
17.
Int Immunopharmacol ; 133: 112082, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38652958

RESUMO

Psoriasis is an incurable immune-mediated disease affecting the skin or the joints. There are continuing studies on drugs for psoriasis prevention and treatment. This research found that Geniposide (GE) significantly thinned IMQ mice's skin lesions, reduced the scales, and lowered the presence of inflammatory cells in the pathology in a dose-dependent manner. GE inhibited IL-23, IL-22, IL-17A, IL-12, IL-6, and TNF-α levels in psoriatic mice serum. AKT1, TNF, TLR4, MMP9, MAPK3, and EGFR were selected as the top 6 targets of GE against psoriasis via network pharmacology, and GE-TLR4 has the most robust docking score value by molecular docking. Taken together, GE significantly inhibited TLR4 and MMP9 protein expression and influenced MyD88/NF-κB p65 signaling pathway. Finally, TLR4 was verified as the critical target of GE, which engaged in immunomodulatory activities and reduced MMP9 production in LPS and TAK-242-induced HaCaT cells. GE had a medium affinity for TLR4, and the KD value was 1.06 × 10-5 M. GE is an effective treatment and preventative strategy for psoriasis since it impacts TLR4.


Assuntos
Iridoides , Metaloproteinase 9 da Matriz , Fator 88 de Diferenciação Mieloide , Psoríase , Transdução de Sinais , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , Animais , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Humanos , Psoríase/tratamento farmacológico , Psoríase/imunologia , Iridoides/farmacologia , Iridoides/uso terapêutico , Camundongos , Fator de Transcrição RelA/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Pele/imunologia , Pele/metabolismo , Citocinas/metabolismo , Masculino , Simulação de Acoplamento Molecular , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células HaCaT , Imiquimode , Linhagem Celular
18.
Mol Med ; 30(1): 52, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641575

RESUMO

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.


Assuntos
Polietilenos , Polipropilenos , Dermatopatias , Fator de Crescimento Transformador beta , Animais , Camundongos , Bleomicina/efeitos adversos , Colágeno/metabolismo , Fibrose/tratamento farmacológico , Hidrogéis/química , Hidrogéis/farmacologia , Polietilenos/farmacologia , Polipropilenos/farmacologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Dermatopatias/induzido quimicamente , Dermatopatias/tratamento farmacológico , Dermatopatias/metabolismo , Proteínas Smad/efeitos dos fármacos , Proteínas Smad/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
19.
Sci Rep ; 14(1): 9336, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653997

RESUMO

Skin cancer is the most prevalent kind of cancer in people. It is estimated that more than 1 million people get skin cancer every year in the world. The effectiveness of the disease's therapy is significantly impacted by early identification of this illness. Preprocessing is the initial detecting stage in enhancing the quality of skin images by removing undesired background noise and objects. This study aims is to compile preprocessing techniques for skin cancer imaging that are currently accessible. Researchers looking into automated skin cancer diagnosis might use this article as an excellent place to start. The fully convolutional encoder-decoder network and Sparrow search algorithm (FCEDN-SpaSA) are proposed in this study for the segmentation of dermoscopic images. The individual wolf method and the ensemble ghosting technique are integrated to generate a neighbour-based search strategy in SpaSA for stressing the correct balance between navigation and exploitation. The classification procedure is accomplished by using an adaptive CNN technique to discriminate between normal skin and malignant skin lesions suggestive of disease. Our method provides classification accuracies comparable to commonly used incremental learning techniques while using less energy, storage space, memory access, and training time (only network updates with new training samples, no network sharing). In a simulation, the segmentation performance of the proposed technique on the ISBI 2017, ISIC 2018, and PH2 datasets reached accuracies of 95.28%, 95.89%, 92.70%, and 98.78%, respectively, on the same dataset and assessed the classification performance. It is accurate 91.67% of the time. The efficiency of the suggested strategy is demonstrated through comparisons with cutting-edge methodologies.


Assuntos
Algoritmos , Dermoscopia , Redes Neurais de Computação , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/patologia , Dermoscopia/métodos , Processamento de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/métodos , Pele/patologia , Pele/diagnóstico por imagem
20.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 233-240, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38650128

RESUMO

Skin photoaging affects appearance and is associated with a variety of skin diseases, even skin cancer. Therefore, the prevention and treatment of skin photoaging is very important. However, there is a lack of effective evaluation methods, so it is an urgent problem to explore a comprehensive, non-invasive and in vivo evaluation method. Adipose-derived mesenchymal stem cells (ADSCs) are widely used to improve skin conditions as easier to obtain and positive effects. Recently, as the development of ultrasound technology, skin ultrasound has been widely used. Changes in skin layer and structure can be observed by high-frequency ultrasound (HFUS). In addition, Shear wave elastography (SWE) technology can be used to monitor the change of skin hardness. However, it is necessary to further explore the ultrasound parameters in interpreting histological changes. We simulate the progression and treatment process of human skin photoaging by using UVB-induced nude mice skin photoaging model and ADSCs injection. The analysis of the degree and therapeutic effect of skin photoaging was conducted by HFUS, SWE and to verify with histopathology. Our study aims to clarify the value of HFUS combined SWE techniques in evaluating the degree and therapeutic efficacy of skin photoaging, which provides theoretical basis for diagnosis and treatment evaluation systems.


Assuntos
Células-Tronco Mesenquimais , Camundongos Nus , Envelhecimento da Pele , Pele , Raios Ultravioleta , Animais , Envelhecimento da Pele/efeitos da radiação , Células-Tronco Mesenquimais/citologia , Humanos , Pele/efeitos da radiação , Pele/patologia , Tecido Adiposo/citologia , Técnicas de Imagem por Elasticidade , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Feminino
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