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1.
Front Immunol ; 15: 1360618, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827737

RESUMEN

Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (i.e., IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed.


Asunto(s)
Biomarcadores , Vesículas Extracelulares , Psoriasis , Humanos , Psoriasis/inmunología , Psoriasis/metabolismo , Psoriasis/etiología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/inmunología , Animales , Piel/patología , Piel/inmunología , Piel/metabolismo , Microambiente Celular/inmunología
2.
Arch Dermatol Res ; 316(6): 316, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822884

RESUMEN

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.


Asunto(s)
Liberación de Fármacos , Emulsiones , Geles , Metotrexato , Absorción Cutánea , Metotrexato/administración & dosificación , Metotrexato/química , Metotrexato/farmacocinética , Humanos , Absorción Cutánea/efectos de los fármacos , Reología , Lípidos/química , Administración Cutánea , Piel/metabolismo , Piel/efectos de los fármacos , Administración Tópica , Sistemas de Liberación de Medicamentos/métodos , Animales , Tamaño de la Partícula , Portadores de Fármacos/química , Nanogeles/química
3.
Front Cell Infect Microbiol ; 14: 1355679, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841110

RESUMEN

Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid-derived metabolites: trans-10-cis-15-octadecadienoic acid (t10,c15-18:2) and cis-9-cis-15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2-but not c9,c15-18:2-attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid-derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis-induced inflammation.


Asunto(s)
Modelos Animales de Enfermedad , Regulación hacia Abajo , Ácidos Grasos Omega-3 , Factor A de Crecimiento Endotelial Vascular , Animales , Ratones , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/farmacología , Dermatitis por Contacto/metabolismo , Dinitrofluorobenceno , Piel/metabolismo , Piel/patología , Queratinocitos/metabolismo , Queratinocitos/efectos de los fármacos , Femenino , Dermatitis Alérgica por Contacto/metabolismo , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Heces/química , Heces/microbiología
4.
AAPS PharmSciTech ; 25(5): 130, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844611

RESUMEN

Naringenin (NRG) inhibits the fungal 17ß-hydroxysteroid dehydrogenase accountable for ergosterol synthesis in Candida albicans (C. albicans), a causative agent for cutaneous candidiasis. In present research, NRG was complexed with ZnO nanomaterial (NRG-Zn2+) to synthesize NRG-Zn2+ nanocomposites. The particle size and ζ-potential of NRG-Zn2+ nanocomposites were respectively estimated to be 180.33 ± 1.22-nm and - 3.92 ± 0.35-mV. In silico data predicted the greater affinity of NRG-Zn2+ nanocomposite for 14α-demethylase and ceramide in comparison to NRG alone. Later, NRG-Zn2+ nanocomposites solution was transformed in to naringenin-zinc oxide nanocomposites loaded chitosan gel (NRG-Zn-CS-Gel) with viscosity and firmness of 854806.7 ± 52386.43 cP and 698.27 ± 10.35 g, respectively. The ex-vivo skin permeation demonstrated 70.49 ± 5.22% skin retention, significantly greater (P < 0.05) than 44.48 ± 3.06% of naringenin loaded chitosan gel (NRG-CS-Gel) and 31.24 ± 3.28% of naringenin solution (NRG Solution). NRG-Zn-CS-Gel demonstrated 6.71 ± 0.84% permeation of NRG with a flux value of 0.046 ± 0.01-µg/cm2/h. The MIC50 of NRG-Zn-CS-Gel against C. albicans was estimated to be 0.156-µg/mL with FICI (fractional inhibitory concentration index) of 0.018 that consequently exhibited synergistic efficacy. Further, NRG-Zn-CS-Gel demonstrated superior antifungal efficacy in C. albicans induced cutaneous candidiasis infection in Balb/c mice. The fungal burden in NRG-Zn-CS-Gel treated group was 109 ± 25 CFU/mL, significantly lower (P < 0.05) than positive control (2260 ± 446 CFU/mL), naringenin loaded chitosan gel (NRG-CS-Gel; 928 ± 127 CFU/mL) and chitosan gel (CS-Gel; 2116 ± 186 CFU/mL) treated mice. Further, histopathology examination and cytokine profiling of TNF-α, IL-1ß and IL-10 revealed the healing of skin and inflammation associated with cutaneous candidiasis infection. In conclusion, NRG-Zn-CS-Gel may be a potential candidate for translating in to a clinical viable topical nanotherapeutic.


Asunto(s)
Antifúngicos , Candida albicans , Quitosano , Flavanonas , Geles , Ratones Endogámicos BALB C , Nanocompuestos , Óxido de Zinc , Animales , Flavanonas/administración & dosificación , Flavanonas/farmacología , Ratones , Candida albicans/efectos de los fármacos , Quitosano/química , Quitosano/administración & dosificación , Nanocompuestos/química , Nanocompuestos/administración & dosificación , Antifúngicos/administración & dosificación , Antifúngicos/farmacología , Antifúngicos/farmacocinética , Óxido de Zinc/administración & dosificación , Óxido de Zinc/farmacología , Óxido de Zinc/química , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Piel/efectos de los fármacos , Piel/microbiología , Candidiasis/tratamiento farmacológico , Polímeros/química , Absorción Cutánea/efectos de los fármacos , Tamaño de la Partícula , Administración Cutánea
5.
J Drugs Dermatol ; 23(6): 463-465, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38834213

RESUMEN

BACKGROUND: Evaluating cleansers and moisturizers provides important information to guide clinicians in the recommendation of these products. This project was performed to visualize skin hydration via heatmap after the use of a gentle skin cleanser (GSC) and moisturizing lotion (ML). METHODS: Half-face, intra-individual open-label study in healthy volunteers. Cleanser was administered in a single application that was then wiped off the face. Moisturizing lotion was applied at least once-daily for one week. Hydration measurements were made at 30 pre-defined points on half of the face, at baseline, and 30 minutes post-application; an additional assessment at week 1 was made for the moisturizing lotion. Heatmaps were generated using Python programming software to interpolate hydration values to colors that were then superimposed onto the volunteer's facial image.  Results: Five subjects completed the cleanser assessments, and 5 subjects completed the 30-minute evaluation for the lotion, with 4 completing the week 1 assessment. There was a visible shift in skin hydration post-GSC application from values approximately in the 12-42 AU (arbitrary unit) range to 30-60 AU at 30 minutes. Similarly, there was a shift in hydration from baseline to 30 minutes that continued to increase through week 1 of ML use. CONCLUSIONS: This innovative heatmap data generation showed a clear, visual change in hydration over time. There was a visible shift in hydration values from baseline to 30 minutes after application of cleanser; hydration also improved after use of moisturizing lotion at 30 minutes and increased after week 1 application.  J Drugs Dermatol. 2024;23(6):463-465.     doi:10.36849/JDD.8221.


Asunto(s)
Cara , Crema para la Piel , Humanos , Crema para la Piel/administración & dosificación , Crema para la Piel/química , Adulto , Femenino , Masculino , Programas Informáticos , Voluntarios Sanos , Persona de Mediana Edad , Emolientes/administración & dosificación , Emolientes/química , Piel/efectos de los fármacos , Piel/metabolismo , Adulto Joven , Cuidados de la Piel/métodos , Administración Cutánea
6.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 85-91, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836676

RESUMEN

Skin photoaging is a skin degenerative disease that causes patients to develop malignant tumors. The existing clinical treatment of photoaging has limitations. This greatly reduces the recovery rate of photoaging patients. Studies have confirmed that Ligusticum wallichii Franch (LWF) monomer tetramethylpyrazine (TMP) alleviates various skin diseases. The combination of traditional Chinese medicine and Western medicine helps with this process. Our research aimed to explore the specific treatment mode and molecular mechanism of TMP in treating skin photoaging. CCK-8 assays were used to evaluate the activity and toxicity of HaCaT cells. ß-galactosidase aging, Carbonyl compound and nitrosylated tyrosine assays were used to analyze the aging of HaCaT cells. ROS assays and ELISA were used to analyze the enrichment of ROS. The molecular docking experiment analyzed the binding of TMP and HIF-1α. qRT-PCR and Western blot were used to detect the activation of skin aging-related pathways. HE staining was used to analyze the thickness of the stratum corneum skin on the back skin of mice. 200µg/L LWF alleviates cellular photoaging and mouse skin photoaging by reducing ROS enrichment. Its monomer TMP plays an important role in this process. The combination of TMP and HIF-1α accelerates the degradation of ROS by activating the Nrf2/ARE signaling pathway. This process reduces the apoptosis of cells damaged by light. In addition, we also found that the combination of TMP and retinoic acid (RA) is more beneficial for the treatment of skin damage caused by light in mice. The combination therapy of TMP and RA alleviates skin oxidative stress response through overexpression of HIF-1α. This plan is beneficial for the treatment of skin photoaging.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia , Pirazinas , Especies Reactivas de Oxígeno , Transducción de Señal , Envejecimiento de la Piel , Vitamina A , Pirazinas/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Animales , Humanos , Especies Reactivas de Oxígeno/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Vitamina A/farmacología , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Células HaCaT , Simulación del Acoplamiento Molecular
7.
Cell Metab ; 36(6): 1287-1301.e7, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38838641

RESUMEN

Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage-tracing mouse studies revealed that sWAT would enter into the large wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested that beige adipocytes in sWAT abundantly express neuregulin 4 (NRG4), which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.


Asunto(s)
Tejido Adiposo Blanco , Piel , Cicatrización de Heridas , Animales , Tejido Adiposo Blanco/metabolismo , Ratones , Piel/metabolismo , Piel/patología , Ratones Endogámicos C57BL , Grasa Subcutánea/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Neurregulinas/metabolismo , Neurregulinas/genética , Masculino , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Tejido Adiposo Pardo/metabolismo , Adipocitos Beige/metabolismo , Macrófagos/metabolismo , Humanos , Miofibroblastos/metabolismo
8.
Arch Dermatol Res ; 316(6): 326, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822910

RESUMEN

Skin aging is one of the visible characteristics of the aging process in humans. In recent years, different biological clocks have been generated based on protein or epigenetic markers, but few have focused on biological age in the skin. Arrest the aging process or even being able to restore an organism from an older to a younger stage is one of the main challenges in the last 20 years in biomedical research. We have implemented several machine learning models, including regression and classification algorithms, in order to create an epigenetic molecular clock based on miRNA expression profiles of healthy subjects to predict biological age-related to skin. Our best models are capable of classifying skin samples according to age groups (18-28; 29-39; 40-50; 51-60 or 61-83 years old) with an accuracy of 80% or predict age with a mean absolute error of 10.89 years using the expression levels of 1856 unique miRNAs. Our results suggest that this kind of epigenetic clocks arises as a promising tool with several applications in the pharmaco-cosmetic industry.


Asunto(s)
Epigénesis Genética , Aprendizaje Automático , MicroARNs , Envejecimiento de la Piel , Piel , Humanos , MicroARNs/genética , Persona de Mediana Edad , Anciano , Adulto , Envejecimiento de la Piel/genética , Anciano de 80 o más Años , Piel/metabolismo , Piel/patología , Femenino , Adulto Joven , Masculino , Adolescente , Perfilación de la Expresión Génica , Relojes Biológicos/genética
9.
J Nanobiotechnology ; 22(1): 307, 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38825668

RESUMEN

Skin aging is characterized by the disruption of skin homeostasis and impaired skin injury repair. Treatment of aging skin has long been limited by the unclear intervention targets and delivery techniques. Engineering extracellular vesicles (EVs) as an upgraded version of natural EVs holds great potential in regenerative medicine. In this study, we found that the expression of the critical antioxidant and detoxification gene Gstm2 was significantly reduced in aging skin. Thus, we constructed the skin primary fibroblasts-derived EVs encapsulating Gstm2 mRNA (EVsGstm2), and found that EVsGstm2 could significantly improve skin homeostasis and accelerate wound healing in aged mice. Mechanistically, we found that EVsGstm2 alleviated oxidative stress damage of aging dermal fibroblasts by modulating mitochondrial oxidative phosphorylation, and promoted dermal fibroblasts to regulate skin epidermal cell function by paracrine secretion of Nascent Polypeptide-Associated Complex Alpha subunit (NACA). Furthermore, we confirmed that NACA is a novel skin epidermal cell protective molecule that regulates skin epidermal cell turnover through the ROS-ERK-ETS-Cyclin D pathway. Our findings demonstrate the feasibility and efficacy of EVs-mediated delivery of Gstm2 for aged skin treatment and unveil novel roles of GSTM2 and NACA for improving aging skin.


Asunto(s)
Vesículas Extracelulares , Fibroblastos , Glutatión Transferasa , ARN Mensajero , Envejecimiento de la Piel , Cicatrización de Heridas , Animales , Ratones , Fibroblastos/metabolismo , Glutatión Transferasa/metabolismo , Vesículas Extracelulares/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genética , Epidermis/metabolismo , Ratones Endogámicos C57BL , Estrés Oxidativo , Piel/metabolismo , Masculino , Humanos , Células Epidérmicas/metabolismo , Células Cultivadas
10.
Sci Rep ; 14(1): 12779, 2024 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834729

RESUMEN

To evaluate the safety and efficacy of combining EW-7197 with irreversible electroporation (IRE) for improving wound healing, 16 male Sprague-Dawley rats were randomly divided into four groups of four rats each after dorsal excisional wound induction: sham control group; oral administration of EW-7197 for 7 days group; one-time application of IRE group; and one-time application of IRE followed by oral administration of EW-7197 for 7 days group. Measurement of wound closure rate, laser Doppler scanning, histological staining (hematoxylin and eosin and Masson's trichrome), and immunohistochemical analyses (Ki-67 and α-SMA) were performed to evaluate the efficacy. Fifteen of 16 rats survived throughout the study. Statistically significant differences in wound closure rates were observed between the combination therapy group and the other three groups (all P < 0.05). The degrees of inflammation, α-SMA, and Ki-67 were reduced in the EW-7197 and IRE monotherapy groups; however, not statistically significant. The fibrosis score exhibited significant reduction in all three treatment groups, with the most prominent being in the combination therapy group. This study concludes that oral administration of EW-7197 combined with IRE demonstrated effectiveness in improving skin wound in a rat excisional model and may serve as a potential alternative for promoting healing outcomes.


Asunto(s)
Electroporación , Ratas Sprague-Dawley , Piel , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Masculino , Ratas , Electroporación/métodos , Piel/metabolismo , Piel/patología , Factor de Crecimiento Transformador beta/metabolismo , Modelos Animales de Enfermedad , Terapia Combinada/métodos
11.
AAPS PharmSciTech ; 25(5): 126, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834910

RESUMEN

In the dynamic landscape of pharmaceutical advancements, the strategic application of active pharmaceutical ingredients to the skin through topical and transdermal routes has emerged as a compelling avenue for therapeutic interventions. This non-invasive approach has garnered considerable attention in recent decades, with numerous attempts yielding approaches and demonstrating substantial clinical potential. However, the formidable barrier function of the skin, mainly the confinement of drugs on the upper layers of the stratum corneum, poses a substantial hurdle, impeding successful drug delivery via this route. Ultradeformable vesicles/carriers (UDVs), positioned within the expansive realm of nanomedicine, have emerged as a promising tool for developing advanced dermal and transdermal therapies. The current review focuses on improving the passive dermal and transdermal targeting capacity by integrating functionalization groups by strategic surface modification of drug-loaded UDV nanocarriers. The present review discusses the details of case studies of different surface-modified UDVs with their bonding strategies and covers the recent patents and clinical trials. The design of surface modifications holds promise for overcoming existing challenges in drug delivery by marking a significant leap forward in the field of pharmaceutical sciences.


Asunto(s)
Administración Cutánea , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Absorción Cutánea , Piel , Humanos , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Absorción Cutánea/fisiología , Absorción Cutánea/efectos de los fármacos , Portadores de Fármacos/química , Animales , Nanopartículas/química , Propiedades de Superficie , Preparaciones Farmacéuticas/administración & dosificación , Preparaciones Farmacéuticas/química , Nanomedicina/métodos
12.
Front Immunol ; 15: 1395479, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835782

RESUMEN

The skin, being a multifaceted organ, performs a pivotal function in the complicated wound-healing procedure, which encompasses the triggering of several cellular entities and signaling cascades. Aberrations in the typical healing process of wounds may result in atypical scar development and the establishment of a persistent condition, rendering patients more vulnerable to infections. Chronic burns and wounds have a detrimental effect on the overall quality of life of patients, resulting in higher levels of physical discomfort and socio-economic complexities. The occurrence and frequency of prolonged wounds are on the rise as a result of aging people, hence contributing to escalated expenditures within the healthcare system. The clinical evaluation and treatment of chronic wounds continue to pose challenges despite the advancement of different therapeutic approaches. This is mainly owing to the prolonged treatment duration and intricate processes involved in wound healing. Many conventional methods, such as the administration of growth factors, the use of wound dressings, and the application of skin grafts, are used to ease the process of wound healing across diverse wound types. Nevertheless, these therapeutic approaches may only be practical for some wounds, highlighting the need to advance alternative treatment modalities. Novel wound care technologies, such as nanotherapeutics, stem cell treatment, and 3D bioprinting, aim to improve therapeutic efficacy, prioritize skin regeneration, and minimize adverse effects. This review provides an updated overview of recent advancements in chronic wound healing and therapeutic management using innovative approaches.


Asunto(s)
Piel , Cicatrización de Heridas , Humanos , Piel/metabolismo , Piel/inmunología , Piel/patología , Piel/lesiones , Animales , Trasplante de Piel
13.
RNA Biol ; 21(1): 31-44, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38828710

RESUMEN

Non-thermal plasma, a partially ionized gas, holds significant potential for clinical applications, including wound-healing support, oral therapies, and anti-tumour treatments. While its applications showed promising outcomes, the underlying molecular mechanisms remain incompletely understood. We thus apply non-thermal plasma to mouse auricular skin and conducted non-coding RNA sequencing, as well as single-cell blood sequencing. In a time-series analysis (five timepoints spanning 2 hours), we compare the expression of microRNAs in the plasma-treated left ears to the unexposed right ears of the same mice as well as to the ears of unexposed control mice. Our findings indicate specific effects in the treated ears for a set of five miRNAs: mmu-miR-144-5p, mmu-miR-144-3p, mmu-miR-142a-5p, mmu-miR-223-3p, and mmu-miR-451a. Interestingly, mmu-miR-223-3p also exhibits an increase over time in the right non-treated ear of the exposed mice, suggesting systemic effects. Notably, this miRNA, along with mmu-miR-142a-5p and mmu-miR-144-3p, regulates genes and pathways associated with wound healing and tissue regeneration (namely ErbB, FoxO, Hippo, and PI3K-Akt signalling). This co-regulation is particularly remarkable considering the significant seed dissimilarities among the miRNAs. Finally, single-cell sequencing of PBMCs reveals the downregulation of 12 from 15 target genes in B-cells, Cd4+ and Cd8+ T-cells. Collectively, our data provide evidence for a systemic effect of non-thermal plasma.


Asunto(s)
Regulación de la Expresión Génica , MicroARNs , Gases em Plasma , Piel , MicroARNs/genética , Animales , Ratones , Piel/metabolismo , Gases em Plasma/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica , Cicatrización de Heridas/efectos de los fármacos , Transducción de Señal , Sistema Inmunológico/metabolismo
14.
J Exp Med ; 221(8)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38861030

RESUMEN

Germline gain-of-function (GOF) variants in STAT3 cause an inborn error of immunity associated with early-onset poly-autoimmunity and immune dysregulation. To study tissue-specific immune dysregulation, we used a mouse model carrying a missense variant (p.G421R) that causes human disease. We observed spontaneous and imiquimod (IMQ)-induced skin inflammation associated with cell-intrinsic local Th17 responses in STAT3 GOF mice. CD4+ T cells were sufficient to drive skin inflammation and showed increased Il22 expression in expanded clones. Certain aspects of disease, including increased epidermal thickness, also required the presence of STAT3 GOF in epithelial cells. Treatment with a JAK inhibitor improved skin disease without affecting local Th17 recruitment and cytokine production. These findings collectively support the involvement of Th17 responses in the development of organ-specific immune dysregulation in STAT3 GOF and suggest that the presence of STAT3 GOF in tissues is important for disease and can be targeted with JAK inhibition.


Asunto(s)
Mutación con Ganancia de Función , Imiquimod , Factor de Transcripción STAT3 , Células Th17 , Animales , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Células Th17/inmunología , Ratones , Humanos , Imiquimod/farmacología , Piel/patología , Piel/metabolismo , Piel/inmunología , Interleucina-22 , Dermatitis/inmunología , Dermatitis/genética , Dermatitis/patología , Dermatitis/metabolismo , Ratones Endogámicos C57BL , Interleucinas/genética , Interleucinas/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Inflamación/genética , Inflamación/metabolismo , Inflamación/inmunología , Inflamación/patología
15.
Photodermatol Photoimmunol Photomed ; 40(4): e12985, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38845468

RESUMEN

BACKGROUND: Photoprotection is the first measure in the prevention and treatment of the deleterious effects that sunlight can cause on the skin. It is well known that prolonged exposure to solar radiation leads to acute and chronic complications, such as erythema, accelerated skin aging, proinflammatory and procarcinogenic effects, and eye damage, among others. METHODS: A better understanding of the molecules that can protect against ultraviolet radiation and their effects will lead to improvements in skin health. RESULTS: Most of these effects of the sunlight are modulated by oxidative stress and proinflammatory mechanisms, therefore, the supplementation of substances that can regulate and neutralize reactive oxygen species would be beneficial for skin protection. Current evidence indicates that systemic photoprotection should be used as an adjunctive measure to topical photoprotection. CONCLUSION: Oral photoprotectors are a promising option in improving protection against damage induced by UVR, as they contain active ingredients that increase the antioxidant effects of the body, complementing other photoprotection measures. We present a review of oral photoprotectors and their effects.


Asunto(s)
Sustancias Protectoras , Rayos Ultravioleta , Humanos , Administración Oral , Antioxidantes/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Piel/metabolismo , Piel/efectos de la radiación , Piel/efectos de los fármacos , Luz Solar/efectos adversos , Rayos Ultravioleta/efectos adversos , Sustancias Protectoras/administración & dosificación
16.
Arch Dermatol Res ; 316(7): 368, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850361

RESUMEN

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids.


Asunto(s)
Queloide , Triamcinolona Acetonida , Queloide/tratamiento farmacológico , Queloide/patología , Humanos , Triamcinolona Acetonida/farmacocinética , Triamcinolona Acetonida/administración & dosificación , Adulto , Femenino , Distribución Tisular , Masculino , Persona de Mediana Edad , Inyecciones Intralesiones , Piel/metabolismo , Piel/patología , Piel/diagnóstico por imagen , Crioultramicrotomía/métodos , Adulto Joven , Imagenología Tridimensional , Sistemas de Liberación de Medicamentos/métodos
17.
Arch Dermatol Res ; 316(7): 349, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850434

RESUMEN

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) with its etiology not yet fully understood. Interleukin (IL)-35 is an inhibitory cytokine that belongs to the IL-12 family. Elevated IL-35 in the plasma and the tumor microenvironment increases tumorigenesis and indicates poor prognosis in different types of malignancies. The objective of this study is to estimate the expression levels of IL-35 in tissue and serum of MF patients versus healthy controls. This case-control study included 35 patients with patch, plaque, and tumor MF as well as 30 healthy controls. Patients were fully assessed, and serum samples and lesional skin biopsies were taken prior to starting treatment. The IL-35 levels were measured in both serum and tissue biopsies by ELISA technique. Both tissue and serum IL-35 levels were significantly higher in MF patients than in controls (P < 0.001) and tissue IL-35 was significantly higher than serum IL-35 in MF patients (P < 0.001). Tissue IL-35 was significantly higher in female patients and patients with recurrent MF compared to male patients and those without recurrent disease (P < 0.001). Since both tissue and serum IL-35 levels are increased in MF, IL-35 is suggested to have a possible role in MF pathogenesis. IL-35 can be a useful diagnostic marker for MF. Tissue IL-35 can also be an indicator of disease recurrence.


Asunto(s)
Interleucinas , Micosis Fungoide , Neoplasias Cutáneas , Humanos , Micosis Fungoide/sangre , Micosis Fungoide/diagnóstico , Micosis Fungoide/patología , Interleucinas/sangre , Interleucinas/metabolismo , Femenino , Masculino , Estudios de Casos y Controles , Persona de Mediana Edad , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Adulto , Piel/patología , Piel/metabolismo , Anciano , Biopsia , Biomarcadores de Tumor/sangre
18.
BMC Genomics ; 25(1): 574, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849762

RESUMEN

BACKGROUND: The Qinghai Tibetan sheep, a local breed renowned for its long hair, has experienced significant deterioration in wool characteristics due to the absence of systematic breeding practices. Therefore, it is imperative to investigate the molecular mechanisms underlying follicle development in order to genetically enhance wool-related traits and safeguard the sustainable utilization of valuable germplasm resources. However, our understanding of the regulatory roles played by coding and non-coding RNAs in hair follicle development remains largely elusive. RESULTS: A total of 20,874 mRNAs, 25,831 circRNAs, 4087 lncRNAs, and 794 miRNAs were annotated. Among them, we identified 58 DE lncRNAs, 325 DE circRNAs, 924 DE mRNAs, and 228 DE miRNAs during the development of medullary primary hair follicle development. GO and KEGG functional enrichment analyses revealed that the JAK-STAT, TGF-ß, Hedgehog, PPAR, cGMP-PKG signaling pathway play crucial roles in regulating fibroblast and epithelial development during skin and hair follicle induction. Furthermore, the interactive network analysis additionally identified several crucial mRNA, circRNA, and lncRNA molecules associated with the process of primary hair follicle development. Ultimately, by investigating DEmir's role in the ceRNA regulatory network mechanism, we identified 113 circRNA-miRNA pairs and 14 miRNA-mRNA pairs, including IGF2BP1-miR-23-x-novel-circ-01998-MSTRG.7111.3, DPT-miR-370-y-novel-circ-005802-MSTRG.14857.1 and TSPEAR-oar-miR-370-3p-novel-circ-005802- MSTRG.10527.1. CONCLUSIONS: Our study offers novel insights into the distinct expression patterns of various transcription types during hair follicle morphogenesis, establishing a solid foundation for unraveling the molecular mechanisms that drive hair development and providing a scientific basis for selectively breeding desirable wool-related traits in this specific breed.


Asunto(s)
Redes Reguladoras de Genes , Folículo Piloso , MicroARNs , ARN Circular , ARN Largo no Codificante , ARN Mensajero , Animales , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , ARN Circular/genética , ARN Circular/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Ovinos/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Perfilación de la Expresión Génica , Piel/metabolismo , Transcriptoma , Feto/metabolismo
19.
Arch Dermatol Res ; 316(7): 348, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849562

RESUMEN

This study investigates the mechanism through which paeoniflorin inhibits TSLP expression to regulate dendritic cell activation in corticosteroid-dependent dermatitis treatment. Utilizing databases like TCMSP, we identified paeoniflorin's components, targets, and constructed networks. Molecular docking and gene enrichment analysis helped pinpoint key targets and pathways affected by paeoniflorin. In vitro and in vivo models were used to study CD80, CD86, cytokines, T-cell activation, skin lesions, histopathological changes, TSLP, CD80, and CD86 expression. Our study revealed paeoniflorin's active constituent targeting IL-6 in corticosteroid-dependent dermatitis. In vitro experiments demonstrated reduced TSLP expression, CD80, CD86, and cytokine secretion post-paeoniflorin treatment. In vivo, paeoniflorin significantly decreased skin lesion severity, cytokine levels, TSLP, CD80, and CD86 expression. The study highlights paeoniflorin's efficacy in inhibiting TSLP expression and suppressing dendritic cell activation in corticosteroid-dependent dermatitis, suggesting its potential as a therapeutic intervention. Additionally, it offers insights into the complex molecular mechanisms underlying paeoniflorin's anti-inflammatory properties in treating corticosteroid-dependent dermatitis.


Asunto(s)
Citocinas , Células Dendríticas , Glucósidos , Monoterpenos , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Glucósidos/farmacología , Glucósidos/uso terapéutico , Animales , Citocinas/metabolismo , Monoterpenos/farmacología , Monoterpenos/uso terapéutico , Humanos , Ratones , Dermatitis/tratamiento farmacológico , Dermatitis/inmunología , Dermatitis/metabolismo , Interleucina-6/metabolismo , Simulación del Acoplamiento Molecular , Piel/patología , Piel/efectos de los fármacos , Piel/inmunología , Piel/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Modelos Animales de Enfermedad , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Masculino , Linfopoyetina del Estroma Tímico , Activación de Linfocitos/efectos de los fármacos
20.
Exp Dermatol ; 33(6): e15100, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38840387

RESUMEN

Skin wound healing is driven by proliferation, migration and differentiation of several cell types that are controlled by the alterations in the gene expression programmes. Brahma Gene 1 (BRG1) (also known as SMARCA4) is a core ATPase in the BRG1 Associated Factors (BAF) ATP-dependent chromatin remodelling complexes that alter DNA-histone interaction in chromatin at the specific gene regulatory elements resulting in increase or decrease of the target gene transcription. Using siRNA mediated suppression of BRG1 during wound healing in a human ex vivo and in vitro (scratch assay) models, we demonstrated that BRG1 is essential for efficient skin wound healing by promoting epidermal keratinocytes migration, but not their proliferation or survival. BRG1 controls changes in the expression of genes associated with gene transcription, response to wounding, cell migration and cell signalling. Altogether, our data revealed that BRG1 play positive role in skin repair by promoting keratinocyte migration and impacting the genes expression programmes associated with cell migration and cellular signalling.


Asunto(s)
Movimiento Celular , ADN Helicasas , Queratinocitos , Proteínas Nucleares , Transducción de Señal , Factores de Transcripción , Cicatrización de Heridas , Humanos , Queratinocitos/metabolismo , ADN Helicasas/metabolismo , ADN Helicasas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Piel/metabolismo , Proliferación Celular , ARN Interferente Pequeño
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