RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. AIM OF THE STUDY: To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. MATERIALS AND METHODS: The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. RESULTS: FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and ß-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. CONCLUSIONS: FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.
Assuntos
Congelamento das Extremidades , Microcirculação , Cicatrização , Congelamento das Extremidades/tratamento farmacológico , Animais , Microcirculação/efeitos dos fármacos , Masculino , Cicatrização/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/irrigação sanguínea , Pele/patologia , Apoptose/efeitos dos fármacos , Ratos , Modelos Animais de Doenças , Camundongos , Administração Tópica , Ratos Sprague-Dawley , Óleos de Plantas/farmacologia , Óleos de Plantas/uso terapêutico , Extratos Vegetais/farmacologiaRESUMO
This paper aims to evaluate the acoustic radiation characteristics of thin plates featuring a layer of small-scale biomimetic shark skin type additive surface treatment. The shark skin dermal denticles are modelled as point masses arranged in a bi-directional pattern on both the upper and lower surfaces of the plate. The governing equations are obtained through a variational approach, incorporating the Dirac Delta function in the derivation of the proposed semi-analytical model for the shark skin layer. A semi-analytical method based on the Rayleigh-Ritz formulation is utilized to analyze the vibrations of these plates with surface modification. The sound radiation characteristics are then derived from the solution of the Rayleigh integral. A comprehensive investigation is performed on the influence of surface modification on different vibro-acoustic characteristics, using a continuous structural mode and power transfer matrix-based approach. Notable observations include a reduction in peak vibro-acoustic responses with dense denticle arrangements, especially at resonance, demonstrating a direct relationship with mass ratios, i.e., the ratio of denticle mass to plate mass. The study further reveals a shift of vibro-acoustic responses towards low frequencies with an increase in mass ratios. A thorough comparative study indicates that while additive surface modifications inspired by shark skin may weaken sound radiation characteristics at resonance frequencies, a reverse effect can be observed at intermittent operational frequencies.
Assuntos
Acústica , Tubarões , Pele , Animais , Pele/efeitos da radiação , Som , Propriedades de Superfície , Vibração , Biomimética/métodosRESUMO
Apparent skin age can be determined by several clinical measurements and may differ from chronological age, hence defining age acceleration/deceleration (Age A/D). Using data from 360 women with dermatological scoring of 21 clinical signs, we defined 3 well-separated co-occurring classes capturing the dryness, the elasticity and the oily nature of the skin. We related the risk of each clinical signs to the stratum corneum levels of 5 pre-selected proteins, we identified specific chronological age-adjusted signatures of each clinical sign. Using variable selection approaches, we identified 6 (of the 21) clinical signs which were jointly predictive of chronological age and used to define the clinical skin age, and subsequently age A/D. Applying univariate and multivariate approaches we found that stratum corneum levels of insulin degrading enzyme (IDE) was protective against (ß = - 1.74, p = 3.3 × 10-6; selection proportion > 90%) accelerated skin ageing. In conclusion, our results support the fact that molecular markers found in the stratum corneum could predict skin ageing acceleration/deceleration.
Assuntos
Biomarcadores , Envelhecimento da Pele , Humanos , Feminino , Envelhecimento da Pele/fisiologia , Biomarcadores/metabolismo , Pessoa de Meia-Idade , Adulto , Epiderme/metabolismo , Idoso , Pele/metabolismo , Adulto JovemRESUMO
The development of effective therapy is necessary because the patients have to contend with long-term therapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certain shortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7 nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. The solubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.
Assuntos
Antifúngicos , Géis , Imidazóis , Nanopartículas , Tamanho da Partícula , Pele , Solubilidade , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Nanopartículas/química , Pele/metabolismo , Pele/efeitos dos fármacos , Animais , Imidazóis/administração & dosagem , Imidazóis/farmacocinética , Imidazóis/química , Imidazóis/farmacologia , Administração Tópica , Química Farmacêutica/métodos , Absorção Cutânea/efeitos dos fármacos , Lipídeos/química , Portadores de Fármacos/química , Administração Cutânea , Excipientes/química , Liberação Controlada de FármacosRESUMO
A novel bacterial isolate A520T (A520T = CBAS 737T = CAIM 1944T) was obtained from the skin of bandtail puffer fish Sphoeroides spengleri (Tetraodontidae Family), collected in Arraial do Cabo (Rio de Janeiro, Brazil). A520T is Gram-stain-negative, flagellated and aerobic bacteria. Optimum growth occurs at 25-30 °C in the presence of 3% NaCl. The genome sequence of the novel isolate consisted of 4.5 Mb (4082 coding genes and G+C content of 41.1%). The closest phylogenetic neighbor was Pseudoalteromonas shioyasakiensis JCM 18891T (97.9% 16S rRNA sequence similarity, 94.8% Average Amino Acid Identity, 93% Average Nucleotide Identity and 51.8% similarity in Genome-to-Genome-Distance). Several in silico phenotypic features are useful to differentiate A520T from its closest phylogenetic neighbors, including trehalose, D-mannose, cellobiose, pyrrolidonyl-beta-naphthylamide, starch hydrolysis, D-xylose, lactose, tartrate utilization, sucrose, citrate, glycerol, mucate and acetate utilization, malonate, glucose oxidizer, gas from glucose, nitrite to gas, L-rhamnose, ornithine decarboxylase, lysine decarboxylase and yellow pigment. The genome of the novel species contains 3 gene clusters (~ 66.81 Kbp in total) coding for different types of bioactive compounds that could indicate ecological roles pertaining to the bandtail puffer fish host. Based on genome-based taxonomic approach, strain A520T (A520T = CBAS 737T = CAIM 1944T) is proposed as a new species, Pseudoalteromonas simplex sp. nov.
Assuntos
Composição de Bases , DNA Bacteriano , Filogenia , Pseudoalteromonas , RNA Ribossômico 16S , Pele , Tetraodontiformes , Animais , Pseudoalteromonas/genética , Pseudoalteromonas/classificação , Pseudoalteromonas/isolamento & purificação , RNA Ribossômico 16S/genética , Tetraodontiformes/microbiologia , DNA Bacteriano/genética , Pele/microbiologia , Genoma Bacteriano , Brasil , Técnicas de Tipagem Bacteriana , Ácidos Graxos/química , Ácidos Graxos/análise , Análise de Sequência de DNARESUMO
Measurement of ethanol above the skin surface (supradermal) is used to monitor blood alcohol concentrations (BAC) in both legal and consumer settings. Previously, the relationship between supradermal alcohol concentration (SAC) and BAC was described using partial and ordinary differential equations (PDE model: J. Appl. Physiol. 100: 649-55, 2006). Using a range of BAC profiles by varying absorption times and peak concentrations, the PDE model accurately predicted experimental measures of SAC. Recently, other mathematical models have relied on the PDE model. This paper proposes a new approach to modeling transdermal ethanol kinetics using a mass transfer coefficient and only ordinary differential equations (ODE model). Using a range of BAC profiles, the ODE model performed very similarly to the PDE model. The ODE model had slightly slower washout rates and slightly slower times to peak SAC and to zero SAC. Similar to the PDE model, a sensitivity analysis on the ODE model showed changes in solubility and diffusivity within the stratum corneum, stratum corneum thickness, and the volume of gas above the skin affected model performance. This new model will streamline integration into larger physiologic models, reduce computation time, and decrease the time to transform skin alcohol measurements to blood alcohol concentrations.
Assuntos
Etanol , Modelos Biológicos , Absorção Cutânea , Pele , Etanol/administração & dosagem , Etanol/farmacocinética , Etanol/sangue , Humanos , Pele/metabolismo , Cinética , Concentração Alcoólica no Sangue , Administração CutâneaRESUMO
BACKGROUND: Histopathological analysis represents the gold standard in clinical practice for diagnosing skin neoplasms. While the current diagnostic workflow has specialized in producing robust and accurate results, interpreting tissue architecture and malignant cellular morphology correctly remains one of the greatest challenges for pathologists. This paper aims to explore the prospect of applying x-ray virtual histology to human skin tumor excisions and correlating it with the histological validation. MATERIALS AND METHODS: Seven skin biopsies containing intriguing melanoma types and pigmented skin lesions were scanned using x-ray Computed micro-Tomography (µCT) and then sectioned for conventional histology assessment. RESULTS: The tissue microarchitecture reconstructed by µCT offers detailed insights into diagnosing the malignancy or benignity of the skin lesions. Three-dimensional reconstruction via x-ray virtual histology reveals infiltrative patterns in basal cell carcinoma and evaluated invasiveness in melanoma. The technology enables the identification of pagetoid distributions of neoplastic cells and the assessment of melanoma depth in three dimensions. CONCLUSION: Although the proposed approach is not intended to replace conventional histology, the non-destructive nature of the sample and the clarity provided by virtual inspection demonstrate the promising impact of µCT as a valid support method prior to conventional histological sectioning. Indeed, µCT images can suggest the optimal sectioning position before using a microtome, as is commonly performed in histological practice. Moreover, the three-dimensional nature of the proposed approach paves the way for a more accurate assessment of significant prognostic factors in melanoma, such as Breslow thickness, by considering the whole micro-volume rather than a two-dimensional observation.
Assuntos
Carcinoma Basocelular , Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Melanoma/diagnóstico por imagem , Melanoma/patologia , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/patologia , Microtomografia por Raio-X/métodos , Imageamento Tridimensional/métodos , Biópsia , Pele/diagnóstico por imagem , Pele/patologiaRESUMO
Th17 cells play crucial roles in host defense and the pathogenesis of autoimmune diseases in the skin. While their differentiation mechanisms have been extensively studied, the origin of skin Th17 cells remains unclear. In this study, we analyzed single-cell RNA-sequencing data and identify the presence of Th17 cells in the human thymus. Thymic Th17 cells were characterized by high expression levels of Sphingosine-1-Phosphate Receptor 1 (S1PR1), a receptor crucial for T cell egress from lymphoid tissues. In mice, Th17 cell-specific knockout of S1pr1 resulted in the accumulation of Th17 cells in the thymus and a corresponding decrease in their numbers in the skin. Th17 cells that accumulated in the thymus exhibited a lower IL-17A production capacity compared to those in the skin, indicating that the local environment in the skin is important for maintaining the Th17 cell phenotype. Additionally, using a murine psoriasis model, we demonstrated that Th17 cell-specific knockout of S1pr1 reduced their migration to the inflamed skin, thereby ameliorating disease progression. Collectively, our data suggest that S1PR1 mediates Th17 cell migration from the thymus to the skin, thereby modulating their functional engagement in both homeostatic and inflammatory conditions.
Assuntos
Movimento Celular , Camundongos Knockout , Psoríase , Pele , Receptores de Esfingosina-1-Fosfato , Células Th17 , Timo , Animais , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/genética , Células Th17/imunologia , Células Th17/metabolismo , Pele/imunologia , Pele/metabolismo , Pele/patologia , Camundongos , Humanos , Timo/imunologia , Timo/metabolismo , Timo/citologia , Psoríase/imunologia , Psoríase/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , FemininoRESUMO
PURPOSE: This study aimed to evaluate the effects of ozone therapy applied topically and/or by bagging on the healing of clean wounds induced in rat's skin. METHODS: One hundred and twenty male rats of about 16 weeks old was divided into five groups: G1) saline solution (0.9%); G2) sunflower oil; G3) ozonated sunflower oil; G4) ozone bagging; G5) association of ozonated sunflower oil and ozone bagging. The wounds were evaluated through macroscopic, morphometric, histopathologic, and tensile strength analyses. RESULTS: Analysis among groups showed a lower percentage of wound contraction in G1 compared to G4 only in M7D. The tensile strength of the wounds showed differences among groups in the seventh (M7D) and the 14th (M14D) postoperative day, and among time points in G1 (M14D > M7D). The elongation of the wounds showed differences in G3 (M7D > M14D). Histological evaluation of the wounds showed significant change in bleeding, mixed to mononuclear infiltrate, congestion, and tissue disorganization for tissue organization between groups and time points. CONCLUSIONS: Ozone therapy applied topically and/or by bagging was not deleterious to the healing of clean wounds induced in rat's skin, but ozone bagging showed the best contribution to the healing process.
Assuntos
Ozônio , Ratos Wistar , Pele , Resistência à Tração , Cicatrização , Animais , Ozônio/administração & dosagem , Ozônio/uso terapêutico , Ozônio/farmacologia , Cicatrização/efeitos dos fármacos , Masculino , Pele/lesões , Pele/efeitos dos fármacos , Pele/patologia , Ratos , Resistência à Tração/efeitos dos fármacos , Óleo de Girassol , Administração Tópica , Fatores de Tempo , Resultado do Tratamento , Modelos Animais de Doenças , Reprodutibilidade dos TestesRESUMO
It's crucial for skin to establish efficient defense strategies. Liu et al. reveal that the transcription factor ZNF750 recruits the histone demethylase KDM1A to silence pattern recognition receptors in the outer epidermis, making their expression limited to deeper, undifferentiated keratinocytes to address threats penetrating the skin.
Assuntos
Queratinócitos , Pele , Fatores de Transcrição , Humanos , Queratinócitos/metabolismo , Queratinócitos/imunologia , Pele/imunologia , Pele/metabolismo , Animais , Fatores de Transcrição/metabolismo , Histona Desmetilases/metabolismo , Epiderme/metabolismo , Epiderme/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Proteínas de Ligação a DNA/metabolismoRESUMO
Cellulite (CLT) is one of the commonly known lipodystrophy syndromes affecting post-adolescent women worldwide. It is topographically characterized by an orange-peel, dimpled skin appearance hence, it is an unacceptable cosmetic problem. CLT can be modulated by surgical procedures such as; liposuction and mesotherapy. But, these options are invasive, expensive and risky. For these reasons, topical CLT treatments are more preferred. Caffeine (CA), is a natural alkaloid that is well-known for its prominent anti-cellulite effects. However, its hydrophilicity hinders its cutaneous permeation. Therefore, in the present study CA was loaded into solid lipid nanoparticles (SLNs) by high shear homogenization/ultrasonication. CA-SLNs were prepared using Compritol® 888 ATO and stearic acid as solid lipids, and span 60 and brij™35, as lipid dispersion stabilizing agents. Formulation variables were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 350 nm), zeta potential (ZP < -25 mV) and polydispersity index (PDI < 0.5). CA-SLN-4 was selected and showed maximized EE (92.03 ± 0.16%), minimized PS (232.7 ± 1.90 nm), and optimum ZP (-25.15 ± 0.65 mV) and PDI values (0.24 ± 0.02). CA-SLN-4 showed superior CA release (99.44 ± 0.36%) compared to the rest CA-SLNs at 1 h. TEM analysis showed spherical, nanosized CA-SLN-4 vesicles. Con-LSM analysis showed successful CA-SLN-4 permeation transepidermally and via shunt diffusion. CA-SLN-4 incorporated into Noveon AA-1® hydrogel (CA-SLN-Ngel) showed accepted physical/rheological properties, and in vitro release profile. Histological studies showed that CA-SLN-Ngel significantly reduced mean subcutaneous fat tissue (SFT) thickness with 4.66 fold (p = 0.035) and 4.16 fold (p = 0.0001) compared to CA-gel, at 7th and 21st days, respectively. Also, significant mean SFT thickness reduction was observed compared to untreated group with 4.83 fold (p = 0.0005) and 3.83 fold (p = 0.0043), at 7th and 21st days, respectively. This study opened new avenue for CA skin delivery via advocating the importance of skin appendages. Hence, CA-SLN-Ngel could be a promising nanocosmeceutical gel for effective CLT treatment.
Assuntos
Cafeína , Celulite , Nanopartículas , Tamanho da Partícula , Animais , Cafeína/administração & dosagem , Cafeína/química , Cafeína/farmacocinética , Celulite/tratamento farmacológico , Ratos , Nanopartículas/química , Absorção Cutânea/fisiologia , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Pele/metabolismo , Pele/efeitos dos fármacos , Permeabilidade , Lipídeos/química , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Ratos Wistar , Administração Tópica , Portadores de Fármacos/química , Feminino , LipossomosRESUMO
Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.
Assuntos
Fibroblastos , Rosácea , Análise de Célula Única , Pele , Transcriptoma , Rosácea/genética , Rosácea/imunologia , Rosácea/patologia , Fibroblastos/metabolismo , Animais , Humanos , Pele/metabolismo , Pele/patologia , Pele/imunologia , Camundongos , Feminino , Interferon gama/metabolismo , Queratinócitos/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Macrófagos/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/imunologia , Células de Schwann/metabolismo , Células de Schwann/patologia , AdultoRESUMO
Bacterial and food allergens are associated with immune-mediated food allergies via the gut-skin axis. However, there has been no data on the potential use of phages to rescue this pathological process. A human triple cell co-culture model incorporating colonocytes (T84 cells), macrophages (THP-1 cells), and hepatocytes (Huh7 cells) was established and infected with Pseudomonas aeruginosa PAO1 (P.a PAO1) in the absence or presence of its KPP22 phage in Dulbecco's Modified Eagle's Medium (DMEM), DMEM+ ovalbumin (OVA), or DMEM+ß-casein media. The physiological health of cells was verified by assessing cell viability and Transepithelial electrical resistance (TEER) across the T84 monolayer. The immune response of cells was investigated by determining the secretions of IL-1ß, IL-8, IL-22, and IL-25. The ability of P.a PAO1 to adhere to and invade T84 cells was evaluated. The addition of either OVA or ß-casein potentiated the P.a PAO1-elicited secretion of cytokines. The viability and TEER of the T84 monolayer were lower in the P.a PAO1+OVA group compared to the P.a PAO1 alone and PAO1+ß-casein groups. OVA and ß-casein significantly increased the adherence and invasion of P.a PAO1 to T84 cells. In the presence of the KPP22 phage, these disruptive effects were abolished. These results imply that: (1) food allergens and bacterial toxic effector molecules exacerbate each other's disruptive effects; (2) food allergen and bacterial signaling at the gut-skin mucosal surface axis depend on a network of bacteria-phage-eukaryotic host interactions; and (3) phages are complementary for the evaluation of pathobiological processes that occur at the interface between bacteria, host cellular milieu, and food antigens because phages intervene in P.a PAO1-, OVA-, and ß-casein-derived inflammation.
Assuntos
Alérgenos , Hipersensibilidade Alimentar , Humanos , Alérgenos/imunologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Pseudomonas aeruginosa/fisiologia , Bacteriófagos/fisiologia , Pele/imunologia , Pele/virologia , Pele/microbiologia , Citocinas/metabolismo , Técnicas de CoculturaRESUMO
Persistent racial disparities in health outcomes have catalyzed legislative reforms and heightened scientific focus recently. However, despite the well-documented properties of skin pigments in binding drug compounds, their impact on therapeutic efficacy and adverse drug responses remains insufficiently explored. This perspective examines the intricate relationships between variation in melanin-based skin pigmentation and pharmacokinetics and -dynamics, highlighting the need for considering diversity in skin pigmentation as a variable to advance the equitability of pharmacological interventions. The article provides guidelines on the selection of New Approach Methods (NAMs) to foster inclusive study designs in preclinical drug development pipelines, leading to an improved level of translatability to the clinic.
Assuntos
Pigmentação da Pele , Humanos , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/genética , Pele/efeitos dos fármacos , Pele/metabolismo , Melaninas , Desenvolvimento de MedicamentosRESUMO
Background: Despite relevant research, the relationship between skin microbiomes and prostate cancer remains controversial. This study utilizes bidirectional Mendelian randomization (MR) analysis combined with meta-analysis to explore the potential link between the two. Objective: This study aims to identify the causal relationship between 150 skin microbiomes and prostate cancer (PCa) using bidirectional Mendelian randomization (MR) and meta-analysis. Methods: This study employed a comprehensive Bidirectional Two-sample MR analysis using publicly available genetic data to ascertain the relationship between 150 skin microbiomes and PCa. We conducted extensive sensitivity analyses, tests for heterogeneity, and assessments of horizontal pleiotropy to ensure the accuracy of our results. Subsequently, we conducted a meta-analysis to strengthen our conclusions' robustness further. Finally, we performed reverse causal verification on the positive skin microbiomes and PCa. Results: After conducting a meta-analysis and multiple corrections of the MR analysis results, our findings reveal a correlation between Neisseria in dry skin and PCa risk, identifying it as a risk factor. The IVW result shows an Odds Ratio (OR) of 1.009 (95% Confidence Interval [CI]: 1.004-1.014, P = 0.027). Furthermore, the reverse MR analysis indicates the absence of an inverse causal relationship between the two. Apart from the identified skin microbiome, no significant associations were found between the other microbiomes and PCa. Conclusions: The study identified a correlation between Neisseria in dry skin, one of the 150 skin microbiomes, and the risk of developing PCa, establishing it as a risk factor for increased susceptibility to PCa.
Assuntos
Análise da Randomização Mendeliana , Microbiota , Neoplasias da Próstata , Pele , Humanos , Neoplasias da Próstata/genética , Neoplasias da Próstata/microbiologia , Masculino , Pele/microbiologia , Pele/patologia , Fatores de RiscoRESUMO
In current toxicological research, 2D cell cultures and animal models are well- accepted and commonly employed methods. However, these approaches have many drawbacks and are distant from the actual environment in human. To embrace this, great efforts have been made to provide alternative methods for non-animal skin models in toxicology studies with the need for more mechanistically informative methods. This review focuses on the current state of knowledge regarding the in vitro 3D skin model methods, with different functional states that correspond to the sustainability in the field of toxicology testing. We discuss existing toxicology testing methods using in vitro 3D skin models which provide a better understanding of the testing requirements that are needed. The challenges and future landscape in using the in vitro 3D skin models in toxicology testing are also discussed. We are confident that the in vitro 3D skin models application may become an important tool in toxicology in the context of risk assessment.
Assuntos
Pele , Humanos , Pele/efeitos dos fármacos , Animais , Testes de Toxicidade/métodos , Modelos Biológicos , Técnicas de Cultura de Tecidos/métodos , Técnicas de Cultura de Células em Três Dimensões/métodosRESUMO
The skin microbiome is essential for skin barrier function because it inhibits pathogen colonization, and decreased microbiome diversity correlates with increased Staphylococcus aureus (S. aureus) burden and atopic dermatitis (AD) severity. Managing S. aureuss-driven AD in clinical practice remains problematic due to complications such as AD exacerbation, impetigo, abscesses, and invasive infections. This project used a modified Delphi process comprising face-to-face discussions followed by a blinded vote to define 5 final consensus statements. A panel of 6 pediatric dermatologists developed a consensus on S. aureus-driven AD exacerbation, challenges in current treatments for AD with secondary bacterial infections, and new developments to improve patient care and outcomes. The panel's 5 consensus statements provide recommendations for dermatologists, pediatricians, and healthcare providers treating patients with secondary infected AD. These recommendations underscore the importance of recognizing and managing S. aureus skin infection in AD clinical practice and promoting antibiotic stewardship to mitigate resistance. The panel defined a significant unmet need for a single topical AD therapy effective against all symptoms, including pruritus, S. aureus-driven AD exacerbation, infection, and inflammation, across AD severity levels. J Drugs Dermatol. 2024;23(10):825-832. doi:10.36849/JDD.8240.
Assuntos
Antibacterianos , Consenso , Técnica Delphi , Dermatite Atópica , Infecções Cutâneas Estafilocócicas , Staphylococcus aureus , Dermatite Atópica/microbiologia , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/terapia , Humanos , Staphylococcus aureus/isolamento & purificação , Infecções Cutâneas Estafilocócicas/diagnóstico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/terapia , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Índice de Gravidade de Doença , Administração Cutânea , Pele/microbiologia , Pele/patologia , Gestão de Antimicrobianos/normas , Progressão da DoençaRESUMO
BACKGROUND: Primary hyperhidrosis (PHH) is a disorder of excessive sweating caused by aberrant cholinergic signaling. Sensitive skin (SS) is a condition of subjective cutaneous hyperreactivity to innocuous stimuli, impacting 40% to 70% of the population. SS is exacerbated by sweat, stress, and heat, suggesting that cholinergic stimulation may contribute to SS flares. OBJECTIVE: To survey PHH sufferers to assess hyperhidrosis (HH) and SS symptom burden. METHODS: An International Review Board (IRB)-exempt survey was disseminated by the International Hyperhidrosis Society. A predictive classification model for SS was built using random forest machine learning algorithms. RESULTS: Of the 637 respondents with PHH, 89% reported SS; and there was a significant association between HH and SS severity scores. Importantly, SS occurred on body sites affected and unaffected by HH. Predictive modeling designated Sensitive Scale-10 (SS-10), a validated questionnaire to gauge SS severity, to be the most helpful in predicting SS in this cohort. LIMITATIONS: Self-reported data. CONCLUSION: These data are the first to propose and support a relationship between SS and HH. SS occurred with greatest frequency at HH-afflicted body sites, but also occurred on unaffected sites, suggesting that sweat is not the sole causative link. Future work can explore cholinergic signaling as a potential link between these conditions. Screening HH patients for SS may be warranted. J Drugs Dermatol. 2024;23(10):882-888. doi:10.36849/JDD.8461.
Assuntos
Hiperidrose , Aprendizado de Máquina , Índice de Gravidade de Doença , Humanos , Hiperidrose/diagnóstico , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Pele/patologia , Sudorese/fisiologia , Inquéritos e Questionários , Adulto Jovem , Autorrelato/estatística & dados numéricosRESUMO
Objective: To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests. Methods: Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope® hybridization and electron microscopy. Results: All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri's bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope® hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions: The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.