RESUMEN
Introduction: Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism's pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets. Methods: Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed. Results: MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol's binding to IRF3, indicating a stable interaction. Conclusion: This study comprehensively elucidates inflammation, immune response, and metabolism's intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo's etiology, informing future research and drug development endeavors.
Asunto(s)
Mano , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Adulto , Femenino , HumanosAsunto(s)
Vesícula/diagnóstico , Pénfigo/diagnóstico , Diagnóstico Diferencial , Humanos , Recién Nacido , MasculinoAsunto(s)
Enfermedades de los Párpados/inmunología , Dermatosis Facial/inmunología , Infecciones por VIH/inmunología , Huésped Inmunocomprometido , Molusco Contagioso/inmunología , Enfermedades de los Párpados/diagnóstico , Enfermedades de los Párpados/patología , Dermatosis Facial/diagnóstico , Dermatosis Facial/patología , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Molusco Contagioso/complicaciones , Molusco Contagioso/diagnóstico , Molusco Contagioso/patologíaRESUMEN
Objective of the study was to investigate the expression and significance of XIAP and c-jun in Condyloma acuminatum. The immunohistochemistry SABC method was adopted to detect the expression of XIAP and c-jun in Condyloma acuminatum. The positive expression rate of XIAP and c-jun in Condyloma acuminatum was 80% (32/40) and 90% (36/40) separately and the intensity of expression was usually ++ ~ +++. While in control group, the positive expression rate of XIAP and c-jun was 27.8% (5/18) and 16.7 % (3/18) separately, and the intensity of expression was - ~ ++. There was statistical significance of the positive expression rate and the expression intensity of XIAP and c-jun between the two groups (P<0.05). Besides, the positive correlation existed between expression of XIAP and c-jun (r=0.306 P<0.01). The over-expression of XIAP and c-jun in Condyloma acuminatum may be associated with the growth of Condyloma acuminatum.
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Condiloma Acuminado/metabolismo , Proteínas Proto-Oncogénicas c-jun/análisis , Proteína Inhibidora de la Apoptosis Ligada a X/análisis , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Toxoplasma gondii has been shown to trigger strong cellular immune responses to heterologous antigens expressed by the parasite in the inbred mouse model. We studied the immune response induced by T. gondii as an effective vaccine vector in chickens and rabbits. RESULTS: T. gondii RH strain was engineered to express the yellow fluorescent protein (YFP) in the cytoplasm. A subcutaneous injection of the transgenic T. gondii YFP in chickens afforded partial protection against the infection of transgenic E. tenella YFP. T. gondii YFP induced low levels of antibodies to YFP in chickens, suggesting that YFP specific cellular immune response was probably responsible for the protective immunity against E. tenella YFP infection. The measurement of T-cell response and IFN-γ production further confirmed that YFP specific Th1 mediated immune response was induced by T. gondii YFP in immunized chickens. The transgenic T. gondii stimulated significantly higher YFP specific IgG titers in rabbits than in chickens, suggesting greater immunogenicity in a T. gondii susceptible species than in a resistant species. Priming with T. gondii YFP and boosting with the recombinant YFP can induce a strong anti-YFP antibody response in both animal species. CONCLUSIONS: Our findings suggest that T. gondii can be used as an effective vaccine vector and future research should focus on exploring avirulent no cyst-forming strains of T. gondii as a live vaccine vector in animals.