RESUMEN

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.

Asunto(s)

Congelación de Extremidades , Microcirculación , Cicatrización de Heridas , Congelación de Extremidades/tratamiento farmacológico , Animales , Microcirculación/efectos de los fármacos , Masculino , Cicatrización de Heridas/efectos de los fármacos , Piel/efectos de los fármacos , Piel/irrigación sanguínea , Piel/patología , Apoptosis/efectos de los fármacos , Ratas , Modelos Animales de Enfermedad , Ratones , Administración Tópica , Ratas Sprague-Dawley , Aceites de Plantas/farmacología , Aceites de Plantas/uso terapéutico , Extractos Vegetales/farmacología

RESUMEN

In defying conventional views that dismissed itch as trivial, I persisted in studying basophils and ILC2s in human skin and atopic dermatitis. My research on JAK inhibitors for itch ultimately led to FDA-approved drugs. This is my story of disregarding categories and definitions-a story about an unconventional path in science that emphasizes innovation over conformity.

Asunto(s)

Dermatitis Atópica , Modelos Animales de Enfermedad , Prurito , Humanos , Animales , Ratones , Dermatitis Atópica/patología , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Historia del Siglo XX , Historia del Siglo XXI , Basófilos/metabolismo , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/farmacología , Piel/patología , Piel/metabolismo

RESUMEN

UV radiation causes long- and short-term skin damage, such as erythema and skin cancer. Therefore, the use of sunscreens is extremely important. However, concerns about UV filter safety have prompted exploration into alternative solutions, with nanotechnology emerging as a promising avenue. This systematic review identified 23 experimental studies utilizing nanocarriers to encapsulate sunscreens with the aim of enhancing their efficacy and safety. Polymeric and lipid nanoparticles are frequently employed to encapsulate both organic and inorganic UV filters along with natural antioxidants. Nanocarriers have demonstrated benefits including reduced active ingredient usage, increased sun protection factor, and mitigated photoinstability. Notably, they also decreased the skin absorption of UV filters. In summary, nanocarriers represent a viable strategy for improving sunscreen formulations, offering enhanced physicochemical properties and bolstered photoprotective effects, thereby addressing concerns regarding UV filter safety and efficacy in cosmetic applications.

Asunto(s)

Nanopartículas , Nanotecnología , Protectores Solares , Rayos Ultravioleta , Protectores Solares/química , Protectores Solares/administración & dosificación , Humanos , Nanopartículas/química , Rayos Ultravioleta/efectos adversos , Nanotecnología/métodos , Portadores de Fármacos/química , Animales , Absorción Cutánea/efectos de los fármacos , Polímeros/química , Antioxidantes/administración & dosificación , Antioxidantes/química , Antioxidantes/farmacología , Piel/metabolismo , Piel/efectos de los fármacos , Factor de Protección Solar/métodos , Lípidos/química

RESUMEN

Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by widespread fibrosis in the skin and several internal organs. Nudix Hydrolase 21 (NUDT2 or CFIm25) downregulation in fibroblasts is known to play detrimental roles in both skin and lung fibrosis. This study aims to investigate the upstream mechanisms that lead to NUDT21 repression in skin fibrosis. We identified transforming growth factor ß (TGFß1) as the primary cytokine that downregulated NUDT21 in normal skin fibroblasts. In the bleomycin-induced dermal fibrosis model, consistent with the peak activation of TGFß1 at the late fibrotic stage, NUDT21 was downregulated at this stage, and delayed NUDT21 knockdown during this fibrotic phase led to enhanced fibrotic response to bleomycin. Further investigation suggested TGFß downregulated NUDT21 through microRNA (miRNA) 181a and 181b induction. Both miR-181a and miR-181b were elevated in bleomycin-induced skin fibrosis in mice and primary fibroblasts isolated from SSc patients, and they directly targeted NUDT21 and led to its downregulation in skin fibroblasts. Functional studies demonstrated that miR-181a and miR-181b inhibitors attenuated bleomycin-induced skin fibrosis in mice in association with decreased NUDT21 expression, while miR-181a and miR-181b mimics promoted bleomycin-induced fibrosis. Overall, these findings suggest a novel role for miR-181a/b in SSc pathogenesis by repressing NUDT21 expression.

Asunto(s)

Bleomicina , Fibroblastos , Fibrosis , MicroARNs , Esclerodermia Sistémica , Piel , MicroARNs/genética , MicroARNs/metabolismo , Animales , Humanos , Ratones , Fibrosis/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Esclerodermia Sistémica/metabolismo , Esclerodermia Sistémica/patología , Esclerodermia Sistémica/genética , Esclerodermia Sistémica/inducido químicamente , Bleomicina/toxicidad , Bleomicina/efectos adversos , Piel/patología , Piel/metabolismo , Femenino , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Ratones Endogámicos C57BL , Factor de Especificidad de Desdoblamiento y Poliadenilación/metabolismo , Factor de Especificidad de Desdoblamiento y Poliadenilación/genética , Células Cultivadas , Regulación hacia Abajo

RESUMEN

The natural process of skin aging is influenced by a variety of factors, including oxidative stress, inflammation, collagen degradation, and UV radiation exposure. The potential of polyphenols in controlling skin aging has been the subject of much investigation throughout the years. Due to their complex molecular pathways, polyphenols, a broad class of bioactive substances present in large quantities in plants, have emerged as attractive candidates for skin anti-aging therapies. This review aims to provide a comprehensive overview of the molecular mechanisms through which polyphenols exert their anti-aging effects on the skin. Various chemical mechanisms contribute to reducing skin aging signs and maintaining a vibrant appearance. These mechanisms include UV protection, moisturization, hydration, stimulation of collagen synthesis, antioxidant activity, and anti-inflammatory actions. These mechanisms work together to reduce signs of aging and keep the skin looking youthful. Polyphenols, with their antioxidant properties, are particularly noteworthy. They can neutralize free radicals, lessening oxidative stress that might otherwise cause collagen breakdown and DNA damage. The anti-inflammatory effects of polyphenols are explored, focusing on their ability to suppress pro-inflammatory cytokines and enzymes, thereby alleviating inflammation and its detrimental effects on the skin. Understanding these mechanisms can guide future research and development, leading to the development of innovative polyphenol-based strategies for maintaining healthy skin.

Asunto(s)

Antiinflamatorios , Antioxidantes , Estrés Oxidativo , Polifenoles , Envejecimiento de la Piel , Piel , Envejecimiento de la Piel/efectos de los fármacos , Polifenoles/farmacología , Polifenoles/uso terapéutico , Humanos , Piel/efectos de los fármacos , Piel/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Rayos Ultravioleta/efectos adversos , Mediadores de Inflamación/metabolismo

RESUMEN

Vitiligo is an acquired autoimmune skin disease characterized by patchy depigmentation of the skin, often accompanied by white hair. The aetiology of vitiligo is complex and difficult to cure, and its disfiguring appearance significantly impacts patients' mental and physical health. Psychological stress is a major factor in inducing and exacerbating vitiligo, as well as affecting its treatment efficacy, though the specific mechanisms remain unclear. Increasing research on the brain-skin axis in skin immunity suggests that psychological stress can influence local skin immunity through this axis, which may play a crucial role in the pathogenesis of vitiligo. This review focuses on the role of brain-skin axis in the pathogenesis of vitiligo, and explores the possible mechanism of brain-skin axis mediating the pathogenesis of vitiligo from the aspects of sympathetic nervous system, hypothalamic-pituitary-adrenal (HPA) axis and hormones and neuropeptides, aiming to provide the necessary theoretical basis for psychological intervention in the prevention and treatment of vitiligo.

Asunto(s)

Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Piel , Estrés Psicológico , Vitíligo , Vitíligo/psicología , Vitíligo/terapia , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Estrés Psicológico/inmunología , Estrés Psicológico/psicología , Piel/patología , Piel/inmunología , Sistema Hipófiso-Suprarrenal/metabolismo , Encéfalo , Sistema Nervioso Simpático/fisiopatología , Neuropéptidos/metabolismo

RESUMEN

BACKGROUND: Abnormal biological behaviour of keratinocytes (KCs) is a critical pathophysiological manifestation of psoriasis. Ferroptosis is programmed cell death induced by the accumulation of lipid reactive oxygen species (ROS) in the presence of increased intracellular iron ions or inhibition of GPX4. OBJECTIVES: The purpose of this study was to investigate the effects of ferroptosis on the biological behaviour of Keratinocytes (KCs) in psoriasis vulgaris and its possible regulatory mechanisms in clinical samples, cells, and mouse models. METHODS: We first examined the differences in the expression of GPX4 and 4-HNE between psoriasis and normal human lesions. And detected KRT6, FLG, and inflammatory cytokines after inducing ferroptosis in animal and cell models by RT-qPCR, Western blot, immunohistochemistry, and flow cytometry. RESULTS: We found that GPX4 was decreased and that the oxidation product 4-hydroxy-2-nonenal (HNE) was increased in the skin lesions of patients with psoriasis vulgaris. The expression level of GPX4 correlates with the severity of skin lesions. Moreover, inducing ferroptosis promoted the expression of FLG and reduced the expression of KRT6 and inflammatory cytokines in vitro, and alleviated the phenotype of skin lesions in vivo. LIMITATIONS: Our study has limitations, notably small sample size. Larger clinical trials are necessary to investigate the association between ferroptosis and disease progression further. More research is necessary to explore how the ferroptosis inducer RSL3 regulates the abnormal biological behaviour of KCs at both cellular and animal levels and establish ferroptosis inhibitors as controls. CONCLUSIONS: This study confirms the existence of ferroptosis in psoriatic lesions, which may be inversely correlated with disease severity. The ferroptosis inducer RSL3 ameliorated psoriatic symptoms by improving the abnormal biological behaviour of KCs.

Asunto(s)

Modelos Animales de Enfermedad , Ferroptosis , Queratinocitos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Psoriasis , Psoriasis/patología , Psoriasis/metabolismo , Psoriasis/inmunología , Ferroptosis/fisiología , Queratinocitos/metabolismo , Queratinocitos/patología , Humanos , Animales , Ratones , Proyectos Piloto , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Aldehídos/metabolismo , Femenino , Masculino , Adulto , Queratina-6/metabolismo , Citocinas/metabolismo , Piel/patología , Piel/metabolismo , Piel/inmunología , Persona de Mediana Edad , Resorcinoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Carbolinas

RESUMEN

Percutaneous delivery is explored as alternative pathway for addressing the drawbacks associated with the oral administration of otherwise efficacious drugs. Short of breaching the skin by physical means, the preference goes to formulation strategies that augment passive diffusion across the skin. One such strategy lies in the use of skin penetration and permeation enhancers notably of hydroxylated solvents like propylene glycol (PG), ethanol (EtOH), and diethylene glycol monoethyl ether (Transcutol®, TRC). In a previous publication, we focused on the role of Transcutol® as enhancer in neat or diluted systems. Herein, we explore its' role in complex formulation systems, including patches, emulsions, vesicles, solid lipid nanoparticles, and micro or nanoemulsions. This review discusses enhancement mechanisms associated with hydroalcoholic solvents in general and TRC in particular, as manifested in multi-component formulation settings alongside other solvents and enhancers. The principles that govern skin penetration and permeation, notably the importance of drug diffusion due to solubilization and thermodynamic activity in the vehicle (formulation), drug solubilization and partitioning in the stratum corneum (SC), and/or solvent drag across the skin into deeper tissue for systemic absorption are discussed. Emphasized also are the interplay between the drug properties, the skin barrier function and the formulation parameters that are key to successful (trans)dermal delivery.

Asunto(s)

Administración Cutánea , Glicoles de Etileno , Permeabilidad , Absorción Cutánea , Piel , Solventes , Absorción Cutánea/fisiología , Absorción Cutánea/efectos de los fármacos , Glicoles de Etileno/química , Humanos , Piel/metabolismo , Animales , Solventes/química , Química Farmacéutica/métodos , Solubilidad , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/química , Nanopartículas/química , Etanol/química , Etanol/administración & dosificación

RESUMEN

BACKGROUND: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. RESULTS: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. CONCLUSION: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.

Asunto(s)

Anticuerpos Antinucleares , Lupus Eritematoso Sistémico , Magnesio , Linfocitos T Reguladores , Animales , Lupus Eritematoso Sistémico/inmunología , Femenino , Ratones , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/sangre , Magnesio/administración & dosificación , Linfocitos T Reguladores/inmunología , Modelos Animales de Enfermedad , Administración Oral , Ratones Endogámicos MRL lpr , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Piel/patología , Piel/inmunología , Piel/efectos de los fármacos , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/patología

RESUMEN

Non-healing skin wounds pose significant clinical challenges, with biologic products like exosomes showing promise for wound healing. Saliva and saliva-derived exosomes, known to accelerate wound repair, yet their extraction is difficult due to the complex environment of oral cavity. In this study, as a viable alternative, we established human minor salivary gland organoids (hMSG-ORG) to produce exosomes (MsOrg-Exo). In vitro, MsOrg-Exo significantly enhanced cell proliferation, migration, and angiogenesis. When incorporated into a GelMA-based controlled-release system, MsOrg-Exo demonstrated controlled release, effectively improving wound closure, collagen synthesis, angiogenesis, and cellular proliferation in a murine skin wound model. Further molecular analyses revealed that MsOrg-Exo promotes proliferation, angiogenesis and the secretion of growth factors in wound sites. Proteomic profiling showed that MsOrg-Exo's protein composition is similar to human saliva and enriched in proteins essential for wound repair, immune modulation, and coagulation. Additionally, MsOrg-Exo was found to modulate macrophage polarization, inducing a shift towards M1 and M2 phenotypes in vitro within 48 h and predominantly towards the M2 phenotype in vivo after 15 days. In conclusion, our study successfully extracted MsOrg-Exo from hMSG-ORGs, confirmed the effectiveness of the controlled-release system combining MsOrg-Exo with GelMA in promoting skin wound healing, and explored the potential role of macrophages in this action.

Asunto(s)

Exosomas , Macrófagos , Organoides , Cicatrización de Heridas , Exosomas/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Humanos , Animales , Macrófagos/metabolismo , Organoides/metabolismo , Ratones , Proliferación Celular , Hidrogeles/química , Hidrogeles/farmacología , Glándulas Salivales/metabolismo , Saliva/química , Saliva/metabolismo , Movimiento Celular , Piel/metabolismo , Piel/lesiones

Asunto(s)

Herpes Simple , Femenino , Humanos , Mejilla/patología , Herpes Simple/diagnóstico , Herpes Simple/patología , Herpes Simple/virología , Herpesvirus Humano 1/aislamiento & purificación , Impétigo/diagnóstico , Piel/patología , Piel/virología , Niño

RESUMEN

Polyurethane materials have good biocompatibility, blood compatibility, mechanical properties, fatigue resistance and processability, and have always been highly valued as medical materials. Polyurethane fibers prepared by electrostatic spinning technology can better mimic the structure of natural extracellular matrices (ECMs), and seed cells can adhere and proliferate better to meet the requirements of tissue repair and reconstruction. The purpose of this review is to present the research progress of electrostatically spun polyurethane fibers in bone tissue engineering, skin tissue engineering, neural tissue engineering, vascular tissue engineering and cardiac tissue engineering, so that researchers can understand the practical applications of electrostatically spun polyurethane fibers in tissue engineering and regenerative medicine.

Asunto(s)

Materiales Biocompatibles , Poliuretanos , Ingeniería de Tejidos , Ingeniería de Tejidos/métodos , Poliuretanos/química , Materiales Biocompatibles/química , Humanos , Andamios del Tejido/química , Medicina Regenerativa , Matriz Extracelular , Huesos , Piel/citología

RESUMEN

BACKGROUND: Atopic dermatitis (AD), psoriasis (PSO), rosacea, and other related immune skin diseases are affected by multiple complex factors such as genetic and microbial components. This research investigates the causal relationships between specific skin microbiota and these diseases by using Mendelian randomization (MR), and Bayesian weighted Mendelian randomization (BWMR). METHODS: We utilized genome-wide association study (GWAS) data to analyze the associations between various skin bacteria and three dermatological diseases. Single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) in MR methods, including inverse variance weighted (IVW), and MR Egger. BWMR was employed to validate results and address pleiotropy. RESULTS: The IVW analysis identified significant associations between specific skin microbiota and dermatological diseases. ASV006_Dry, ASV076_Dry, and Haemophilus_Dry were significantly positively associated with AD, whereas Kocuria_Dry was negatively associated. In PSO, ASV005_Dry was negatively associated, whereas ASV004_Dry, Rothia_Dry, and Streptococcus_Moist showed positive associations. For rosacea, ASV023_Dry was significantly positively associated, while ASV016_Moist, Finegoldia_Dry, and Rhodobacteraceae_Moist were significantly negatively associated. These results were corroborated by BWMR analysis. CONCLUSION: Bacterial species such as Finegoldia, Rothia, and Streptococcus play crucial roles in the pathogenesis of AD, PSO, and rosacea. Understanding these microbial interactions can aid in developing targeted treatments and preventive strategies, enhancing patient outcomes and quality of life.

Asunto(s)

Teorema de Bayes , Dermatitis Atópica , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Microbiota , Polimorfismo de Nucleótido Simple , Humanos , Microbiota/genética , Dermatitis Atópica/microbiología , Dermatitis Atópica/genética , Piel/microbiología , Rosácea/microbiología , Rosácea/genética , Enfermedades de la Piel/microbiología , Enfermedades de la Piel/genética , Psoriasis/microbiología , Psoriasis/genética

RESUMEN

BACKGROUND: Skin cancer is one of the highly occurring diseases in human life. Early detection and treatment are the prime and necessary points to reduce the malignancy of infections. Deep learning techniques are supplementary tools to assist clinical experts in detecting and localizing skin lesions. Vision transformers (ViT) based on image segmentation classification using multiple classes provide fairly accurate detection and are gaining more popularity due to legitimate multiclass prediction capabilities. MATERIALS AND METHODS: In this research, we propose a new ViT Gradient-Weighted Class Activation Mapping (GradCAM) based architecture named ViT-GradCAM for detecting and classifying skin lesions by spreading ratio on the lesion's surface area. The proposed system is trained and validated using a HAM 10000 dataset by studying seven skin lesions. The database comprises 10 015 dermatoscopic images of varied sizes. The data preprocessing and data augmentation techniques are applied to overcome the class imbalance issues and improve the model's performance. RESULT: The proposed algorithm is based on ViT models that classify the dermatoscopic images into seven classes with an accuracy of 97.28%, precision of 98.51, recall of 95.2%, and an F1 score of 94.6, respectively. The proposed ViT-GradCAM obtains better and more accurate detection and classification than other state-of-the-art deep learning-based skin lesion detection models. The architecture of ViT-GradCAM is extensively visualized to highlight the actual pixels in essential regions associated with skin-specific pathologies. CONCLUSION: This research proposes an alternate solution to overcome the challenges of detecting and classifying skin lesions using ViTs and GradCAM, which play a significant role in detecting and classifying skin lesions accurately rather than relying solely on deep learning models.

Asunto(s)

Algoritmos , Aprendizaje Profundo , Dermoscopía , Neoplasias Cutáneas , Humanos , Dermoscopía/métodos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/patología , Interpretación de Imagen Asistida por Computador/métodos , Bases de Datos Factuales , Piel/diagnóstico por imagen , Piel/patología

RESUMEN

The aim of the present study was to evaluate the photothermal effects of a subdermal high-power diode laser at a wavelength (λ) of 1470 nm in the skin of rats. Twenty male Wistar rats were used, divided into 2 groups: placebo laser (PL) and active laser (AL). A high-power diode laser equipment was applied to 5 subdermal vectors on the animal's back region. The results demonstrated that active laser animals showed a better arrangement of collagen fiber bands, an increase in the thickness of the dermis and the number of vessels. Furthermore, animals treated with active laser showed an increased immunoexpression of TGF-ß and VEGF compared to the placebo. The present work demonstrated that the subdermal high-power diode laser increases the vascularization and the expression of factors that enhance skin regeneration and may be promising resource in the esthetic and dermatology clinical treatment of skin rejuvenation.

Asunto(s)

Láseres de Semiconductores , Ratas Wistar , Piel , Animales , Masculino , Ratas , Láseres de Semiconductores/uso terapéutico , Piel/efectos de la radiación , Piel/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Rejuvenecimiento , Modelos Animales

RESUMEN

Malassezia, the most abundant fungal commensal on the mammalian skin, has been linked to several inflammatory skin diseases such as atopic dermatitis, seborrheic dermatitis and psoriasis. This study reveals that epicutaneous application with Malassezia globosa (M. globosa) triggers skin inflammation in mice. RNA-sequencing of the resulting mouse lesions indicates activation of Interleukin-17 (IL-17) signaling and T helper 17 (Th17) cells differentiation pathways by M. globosa. Furthermore, our findings demonstrate a significant upregulation of IL-23, IL-23R, IL-17A, and IL-22 expressions, along with an increase in the proportion of Th17 and pathogenic Th17 cells in mouse skin exposed to M. globosa. In vitro experiments illustrate that M. globosa prompts human primary keratinocytes to secrete IL-23 via TLR2/MyD88/NF-κB signaling. This IL-23 secretion by keratinocytes is shown to be adequate for inducing the differentiation of pathogenic Th17 cells in the skin. Overall, these results underscore the significant role of Malassezia in exacerbating skin inflammation by stimulating IL-23 secretion by keratinocytes and promoting the differentiation of pathogenic Th17 cells.

Asunto(s)

Diferenciación Celular , Interleucina-23 , Queratinocitos , Malassezia , Células Th17 , Malassezia/inmunología , Queratinocitos/microbiología , Queratinocitos/inmunología , Queratinocitos/metabolismo , Células Th17/inmunología , Animales , Interleucina-23/metabolismo , Humanos , Ratones , Transducción de Señal , FN-kappa B/metabolismo , Receptor Toll-Like 2/metabolismo , Interleucina-17/metabolismo , Piel/microbiología , Piel/patología , Piel/inmunología , Modelos Animales de Enfermedad , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Células Cultivadas , Ratones Endogámicos C57BL , Interleucina-22

RESUMEN

Cutaneous mycobacterial infections cause substantial morbidity and are challenging to diagnose and treat. An improved understanding of the dermal immune response to mycobacteria may inspire new therapeutic approaches. We conducted a controlled human infection study with 10 participants who received 2 × 106 CFUs of Mycobacterium bovis bacillus Calmette-Guérin (Tice strain) intradermally and were randomized to receive isoniazid or no treatment. Peripheral blood was collected at multiple time points for flow cytometry, bulk RNA sequencing (RNA-seq), and serum Ab assessments. Systemic immune responses were detected as early as 8 d postchallenge in this M. bovis bacillus Calmette-Guérin-naive population. Injection-site skin biopsies were performed at days 3 and 15 postchallenge and underwent immune profiling using mass cytometry and single-cell RNA-seq, as well as quantitative assessments of bacterial viability and burden. Molecular viability testing and standard culture results correlated well, although no differences were observed between treatment arms. Single-cell RNA-seq revealed various immune and nonimmune cell types in the skin, and communication between them was inferred by ligand-receptor gene expression. Day 3 communication was predominantly directed toward monocytes from keratinocyte, muscle, epithelial, and endothelial cells, largely via the migration inhibitory factor pathway and HLA-E-KLRK1 interaction. At day 15, communication was more balanced between cell types. These data reveal the potential role of nonimmune cells in the dermal immune response to mycobacteria and the utility of human challenge studies to augment our understanding of mycobacterial infections.

Asunto(s)

Mycobacterium bovis , Piel , Humanos , Mycobacterium bovis/inmunología , Piel/inmunología , Piel/microbiología , Piel/patología , Masculino , Adulto , Isoniazida/uso terapéutico , Isoniazida/farmacología , Femenino , Tuberculosis/inmunología , Tuberculosis/microbiología , Adulto Joven , Antituberculosos/uso terapéutico

Asunto(s)

Brazo , Piel , Humanos , Piel/patología , Brazo/patología , Masculino , Niño

RESUMEN

INTRODUCTION: Skin tear (ST) will prolong the hospitalisation time of an older person, increase the cost of medical expenses and the difficulty in care for nursing staff, and seriously affect the quality of life of the older person. Early identification and intervention of the elderly at risk of ST are key factors in preventing the occurrence of ST in older persons. At present, risk factors for ST in older persons have not been systematically evaluated, let alone summarised to analyse risk factors for ST in older persons. Therefore, this systematic review and meta-analysis aims to synthesise existing research on risk factors for ST in older populations. METHODS AND ANALYSIS: The protocol is being reported by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. On 17 September 2023, we will start literature search in PubMed, Embase, Web of Science, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Medline, Chinese Scientific Journal Database, Wan Fang Data Knowledge Service Platform, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database. The language of the included literature is Chinese or English. Using RevMan V.5.4 software, we will perform a systematic review and meta-analysis of the final set of included studies to synthesise the data and draw meaningful conclusions. The Newcastle-Ottawa Quality Assessment Scale and the Agency for Healthcare Research and Quality will be used to assess the quality of the literature. The I2 test will be used to test heterogeneity. ETHICS AND DISSEMINATION: Ethical approval is not needed for this systematic review, as the study will not directly use information from human participants, and the data we use will be extracted from original studies. This systematic review and meta-analysis has been registered at the International Prospective Register of Systematic Reviews (PROSPERO). Once the systematic review and meta-analysis have been completed, we will publish our study in an academic journal. PROSPERO REGISTRATION NUMBER: CRD42023460810.

Asunto(s)

Metaanálisis como Asunto , Piel , Revisiones Sistemáticas como Asunto , Humanos , Factores de Riesgo , Piel/lesiones , Anciano , Proyectos de Investigación , Laceraciones/epidemiología , Calidad de Vida

RESUMEN

The limitations and complexity of traditional noncontact sensors in terms of sensitivity and threshold settings pose great challenges to extend the traditional five human senses. Here, we propose tele-perception to enhance human perception and cognition beyond these conventional noncontact sensors. Our bionic multi-receptor skin employs structured doping of inorganic nanoparticles to enhance the local electric field, coupled with advanced deep learning algorithms, achieving a ΔV/Δd sensitivity of 14.2, surpassing benchmarks. This enables precise remote control of surveillance systems and robotic manipulators. Our long short-term memory-based adaptive pulse identification achieves 99.56% accuracy in material identification with accelerated processing speeds. In addition, we demonstrate the feasibility of using a two-dimensional (2D) sensor matrix to integrate real object scan data into a convolutional neural network to accurately discriminate the shape and material of 3D objects. This promises transformative advances in human-computer interaction and neuromorphic computing.

Asunto(s)

Redes Neurales de la Computación , Humanos , Piel , Aprendizaje Profundo , Algoritmos