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.
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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/farmacologíaRESUMEN
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.
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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/metabolismoRESUMEN
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.
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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 AbajoRESUMEN
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.
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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/metabolismoRESUMEN
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.
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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 , CarbolinasRESUMEN
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.
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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/patologíaRESUMEN
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.
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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/patologíaRESUMEN
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.
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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-22RESUMEN
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.
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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 terapéuticoRESUMEN
Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 µmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.
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Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Envejecimiento de la Piel , Rayos Ultravioleta , Envejecimiento de la Piel/efectos de los fármacos , Animales , Humanos , Rayos Ultravioleta/efectos adversos , Ratones , Estrés Oxidativo/efectos de los fármacos , Metaloproteinasas de la Matriz/metabolismo , Queratinocitos/efectos de los fármacos , Ratones Desnudos , Piel/efectos de los fármacos , Piel/patología , Piel/metabolismo , Piel/efectos de la radiación , Células HaCaT , Masculino , Melaninas/metabolismo , Colágeno/metabolismo , FemeninoRESUMEN
BACKGROUND: Regenerative aesthetics has garnered significant attention. In this toolkit, exosomes are small extracellular vesicles derived from various sources such as platelets. OBJECTIVE: To characterize the cosmetic effect and tolerability of topical human platelet-derived extract (HPE), Intense Serum (Rion Aesthetics, Inc., Rochester, MN), on facial skin rejuvenation after 12 weeks of twice daily use without any confounding aesthetic procedures. MATERIALS AND METHODS: This prospective, single-arm, non-randomized, evaluator-blinded clinical study evaluated subjects at baseline and 12 weeks using participant questionnaires and photo-documentation with Canfield VISIA-CR 3D PRIMOS. The histological evaluation included Masson's Trichrome for collagen and Verhoeff-Van Gieson staining for elastin. Electron microscopy characterized collagen bundle thickness. RESULTS: Fifty-six participants (mean age: 54 years old) were enrolled. Following topical HPE use, 87.3% of subjects reported improvement in facial skin aging including sustained pigment reduction and improvement in luminosity and color evenness at 12 weeks (P≤0.001). Histology revealed a significant increase in collagen fibril thickness at 12 weeks (P≤0.0001). No serious adverse effects. CONCLUSION: This study demonstrates improvement in facial skin health after topical HPE use, supported by collagen and elastin formation in the dermis. The product is well-tolerated, and participants were satisfied with the overall cosmetic outcome. J Drugs Dermatol. 2024;23(9):735-740. doi:10.36849/JDD.8162.
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Plaquetas , Colágeno , Elastina , Cara , Rejuvenecimiento , Envejecimiento de la Piel , Humanos , Persona de Mediana Edad , Envejecimiento de la Piel/efectos de los fármacos , Femenino , Estudios Prospectivos , Colágeno/metabolismo , Masculino , Plaquetas/efectos de los fármacos , Adulto , Anciano , Administración Cutánea , Resultado del Tratamiento , Técnicas Cosméticas/efectos adversos , Piel/efectos de los fármacos , Piel/patología , Método Simple CiegoRESUMEN
Wounds are most commonly caused by accidents, surgery and burns, and can be internal or external. Naturally, the wound healing process can take a long time and lead to scarring. In this study we present a technique to shorten wound healing time and prevent or mitigate scarring using D-mannose that is applied directly on the wound. The results showed that the healing time is almost halved compared to treatment with povidone-iodine solution which is an antiseptic widely used in surgery. D-Mannose is neither an antisepsis nor an antibiotic. We propose a posssible mechanism by which D-mannose binds to D-mannose binding lectin and immediately activates the innate immune system that ultimately phagocytizes pathogens and clears the wound of degraded cells and materials, which reduces inflammation and implicitly wound healing time. D-Mannose also intervenes in the coagulation process by binding to fibrinogen, generating a finer and denser fibrin, which visibly reduces collagen scars. Our findings show that applying D-mannose directly on the wound as a powder shortens wound healing time and visibly attenuates scarring. Apart from the unaesthetic appearance, these scars can also cause a certain tissue dysfunction, regardless of the affected organ.
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Cicatriz , Lectina de Unión a Manosa , Manosa , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Cicatriz/patología , Cicatriz/prevención & control , Lectina de Unión a Manosa/metabolismo , Animales , Humanos , Masculino , Piel/patología , Piel/efectos de los fármacos , Piel/metabolismo , Femenino , Inmunidad Innata/efectos de los fármacosRESUMEN
Lumpy skin disease (LSD) is one of the most economically significant viral diseases of cattle caused by the Lumpy Skin Disease Virus (LSDV), classified as a member of the genus Capripoxvirus and belongs to the family Poxviridae. Nodular skin samples were collected from clinically sick cattle in the districts of Amuru and Wara Jarso Ethiopia to isolate LSD virus. The virus was isolated using primary lamb testis and kidney cells. The isolated LSDV was infected into a healthy calf while maintaining the necessary biosecurity measures to generate skin lesions and to assess disease progression using postmortem examinations. On the fourth day after virus inoculation, the calf developed typical LSD skin nodules with increased rectal temperature, which lasted until the 12th day, when they began to decrease. Viral shedding was detected in nasal, oral, and conjunctival swabs from 6 to 14 days after infection using real-time PCR. Post-mortem tissue specimens tested positive for LSD virus using real-time PCR and virus isolation. This study showed that LSDV were responsible for the LSD outbreaks, and the appearance of typical skin nodules accompanied by fever (> 39.5 °C) defined the virus's virulent status. The experimental infection with the isolated infectious LSDV could serve as a platform for future vaccine evaluation study using an LSDV challenge model.
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Dermatosis Nodular Contagiosa , Virus de la Dermatosis Nodular Contagiosa , Animales , Virus de la Dermatosis Nodular Contagiosa/aislamiento & purificación , Virus de la Dermatosis Nodular Contagiosa/genética , Dermatosis Nodular Contagiosa/virología , Dermatosis Nodular Contagiosa/patología , Bovinos , Piel/virología , Piel/patología , Esparcimiento de Virus , Etiopía , Ovinos , MasculinoRESUMEN
The plasma membrane protein caveolin-1 (CAV-1) regulates signaling by inhibiting a wide range of kinases and other enzymes. Our previous study demonstrated that the downregulation of CAV-1 in psoriatic epidermal cells contributes to inflammation by enhancing JAK/STAT signaling, cell proliferation, and chemokine production. Administration of the CAV-1 scaffolding domain (CSD) peptide suppressed imiquimod (IMQ)-induced psoriasis-like dermatitis. To identify an optimal therapeutic peptide derived from CAV-1, we have compared the efficacy of CSD and subregions of CSD that have been modified to make them water soluble. We refer to these modified peptides as sCSD, sA, sB, and sC. In IMQ-induced psoriasis-like dermatitis, while all four peptides showed major beneficial effects, sB caused the most significant improvements of skin phenotype and number of infiltrating cells, comparable or superior to the effects of sCSD. Phosphorylation of STAT3 was also inhibited by sB. Furthermore, sB suppressed angiogenesis both in vivo in the dermis of IMQ-induced psoriasis mice and in vitro by blocking the ability of conditioned media derived from CAV-1-silenced keratinocytes to inhibit tube formation by HUVEC. In conclusion, sB had similar or greater beneficial effects than sCSD not only by cytokine suppression but by angiogenesis inhibition adding to its ability to target psoriatic inflammation.
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Caveolina 1 , Citocinas , Imiquimod , Neovascularización Patológica , Psoriasis , Factor de Transcripción STAT3 , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Psoriasis/patología , Psoriasis/metabolismo , Caveolina 1/metabolismo , Animales , Ratones , Citocinas/metabolismo , Humanos , Factor de Transcripción STAT3/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Péptidos/farmacología , Péptidos/química , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Modelos Animales de Enfermedad , Agua/química , Solubilidad , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , AngiogénesisRESUMEN
Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant S. aureus (MRSA) strains being a major contributor in both community and hospital settings. S. aureus relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both in vitro and in vivo. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the ΔyjbIH mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the ΔyjbH mutant. This work continues to define the importance of YjbH in the pathogenesis of S. aureus infection as well as identify a new pathway important for Hla production.
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Proteínas Bacterianas , Toxinas Bacterianas , Regulación Bacteriana de la Expresión Génica , Proteínas Hemolisinas , Staphylococcus aureus , Transactivadores , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/genética , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/inmunología , Toxinas Bacterianas/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Staphylococcus aureus/patogenicidad , Staphylococcus aureus/inmunología , Staphylococcus aureus/genética , Ratones , Animales , Transactivadores/genética , Transactivadores/metabolismo , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/patología , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/inmunología , Piel/microbiología , Piel/patología , Piel/inmunología , Factores de Virulencia/genética , Humanos , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/inmunología , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Citocinas/metabolismo , Citocinas/inmunología , Citocinas/genéticaAsunto(s)
Autoanticuerpos , Enfermedades del Colágeno , Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/tratamiento farmacológico , Enfermedades del Colágeno/patología , Enfermedades del Colágeno/diagnóstico , Diagnóstico Diferencial , Autoanticuerpos/sangre , Femenino , Piel/patología , Piel/inmunología , Piel/efectos de los fármacos , Anciano , Biopsia , Masculino , Valor Predictivo de las Pruebas , Autoantígenos/inmunología , LamininaRESUMEN
As it has been revealed that the activation of human immune cells through the activity of intestinal microorganisms such as pro- and prebiotics plays a vital role, controlling the proliferation of beneficial bacteria and suppressing harmful bacteria in the intestine has become essential. The importance of probiotics, especially for skin health and the immune system, has led to the emergence of products in various forms, including probiotics, prebiotics, and parabiotics. In particular, atopic dermatitis (AD) produces hypersensitive immunosuppressive substances by promoting the differentiation and activity of immune regulatory T cells. As a result, it has been in the Th1 and Th2 immune balance through a mechanism that suppresses skin inflammation or allergic immune responses caused by bacteria. Furthermore, an immune mechanism has recently emerged that simultaneously controls the expression of IL-17 produced by Th17. Therefore, the anti-atopic effect was investigated by administering doses of anti-atopic candidate substances (Lactobacilus sakei CVL-001, Lactobacilus casei MCL, and Lactobacilus sakei CVL-001 Lactobacilus casei MCL mixed at a ratio of 4:3) in an atopy model using 2,4-dinitrochlorobenzene and observing symptom changes for 2 weeks to confirm the effect of pro-, para-, and mixed biotics on AD. First, the body weight and feed intake of the experimental animals were investigated, and total IgG and IgM were confirmed through blood biochemical tests. Afterward, histopathological staining was performed using H&E staining, Toluidine blue staining, Filaggrin staining, and CD8 antibody staining. In the treatment group, the hyperproliferation of the epidermal layer, the inflammatory cell infiltration of the dermal layer, the expression of CD8, the expression of filaggrin, and the secretion of mast cells were confirmed to be significantly reduced. Lastly, small intestine villi were observed through a scanning microscope, and scoring evaluation was performed through skin damage. Through these results, it was confirmed that AD was reduced when treated with pro-, para-, and mixed biotics containing probiotics and parabiotics.
Asunto(s)
Dermatitis Atópica , Modelos Animales de Enfermedad , Proteínas Filagrina , Prebióticos , Probióticos , Piel , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Animales , Piel/patología , Piel/inmunología , Ratones , Ratones Endogámicos BALB C , Dinitroclorobenceno , FemeninoRESUMEN
Keloids are characterized histologically by excessive fibroblast proliferation and connective tissue deposition, and clinically by scar tissue extending beyond the original site of skin injury. These scars can cause pruritus, pain, physical disfigurement, anxiety, and depression. As a result, keloid patients often have a diminished quality of life with a disproportionate burden on ethnic minorities. Despite advances in understanding keloid pathology, there is no effective Food and Drug Administration (FDA)-approved pharmacotherapy. Recent studies have highlighted the possible pathologic role of T helper (Th)17 cells and interleukin (IL)-17 in keloid formation, as well as their implication in other inflammatory disorders. This systematic review characterizes the role of Th17 cells and IL-17 in keloid pathogenesis, highlighting this pathway as a potential therapeutic target. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search on PubMed, Embase, MEDLINE, and Web of Science databases on June 5, 2024. The search included terms related to Th17 cells, IL-17, and keloids. Thirteen studies met the inclusion criteria, comprising basic science and bioinformatic studies focusing on Th17 cells and IL-17. Key findings include increased Th17 cell infiltration and IL-17 expression in keloids, IL-17's role in amplifying the inflammatory and fibrotic response via the promotion of IL-6 expression, and IL-17's involvement in upregulating fibrotic markers via SDF-1 and HIF-1α pathways. IL-17 also activates the transforming growth factor beta (TGF-ß)/Smad pathway in keloid fibroblasts. Th17 cells and IL-17 significantly contribute to the inflammatory and fibrotic processes in keloid pathogenesis. Therefore, targeting the IL-17 pathway offers a potential new therapeutic target to improve keloid patients' outcomes. Future research could further elucidate the role of Th17 cells and IL-17 in keloid pathogenesis and assess the safety and efficacy of targeting this pathway in human studies.