Exploring the roles and potential therapeutic strategies of inflammation and metabolism in the pathogenesis of vitiligo: a mendelian randomization and bioinformatics-based investigation.

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.

The relationship between history of thyroid diseases and risk of in-hospital cardiovascular outcomes in patients with atrial fibrillation: Findings From the CCC-AF (Improving Care for Cardiovascular Disease in China-Atrial Fibrillation) Project

Background: Atrial fibrillation (AF) has the close relation to thyroid dysfunction and these two diseases lead to poor cardiovascular outcomes. But the prognostic value of thyroid diseases in AF remains unclear. We aimed to determine whether history of thyroid diseases is associated with risk of in-hospital cardiovascular outcomes in AF.MethodsBased on the data from the CCC-AF (Improving Care for Cardiovascular Diseases in China-Atrial Fibrillation) project, 31,486 inpatients with a definitive diagnosis of AF and record of history of thyroid diseases were included. Logistic regression analysis was performed to investigate the relationship between history of thyroid diseases and risk of in-hospital major adverse cardiovascular events (MACE) in AF.ResultsAmong AF patients, 503 (1.6%) had a history of hypothyroidism, 642 (2.0%) had a history of hyperthyroidism and 30,341 (96.4%) had no thyroid dysfunction. During this hospitalization, 5146 (16.3%) AF patients suffered from MACE. The incidence was 13.1% in hypothyroidism, 16.3% in euthyroidism and 19.0% in hyperthyroidism, in which there was a significant difference among three groups (p=0.028). Multivariable logistic regression analysis revealed that history of hypothyroidism decreased but history of hyperthyroidism increased the risk of in-hospital MACE in AF patients (adjusted odds ratio [OR]=0.603; 95% confidence interval [CI], 0.449–0.811; p=0.001 versus adjusted OR=1.327; 95% CI, 1.060–1.661; p=0.013).ConclusionHistory of hypothyroidism was an independent protective factor, whereas history of hyperthyroidism was an independent risk factor for in-hospital cardiovascular outcomes in AF. Our study indicated that hyperthyroidism should be treated aggressively in order to improve the prognosis of AF. (AU)

Antecedentes: La fibrilación auricular (FA) está estrechamente relacionada con la disfunción tiroidea, y estas 2 enfermedades conducen a resultados cardiovasculares deficientes. Pero el valor pronóstico de las enfermedades tiroideas en la FA sigue sin estar claro. Nuestro objetivo era determinar si la historia de enfermedades tiroideas está asociada con el riesgo de resultados cardiovasculares intrahospitalarios en la FA.MétodosEn base a los datos del proyecto de mejora de la atención de las enfermedades cardiovasculares en China - fibrilación auricular (CCC-FA, por sus siglas en inglés), se incluyeron 31.486 pacientes hospitalizados con un diagnóstico definitivo de FA y un registro de antecedentes de enfermedades tiroideas. Se realizó un análisis de regresión logística para investigar la relación entre la historia de las enfermedades tiroideas y el riesgo de eventos cardiovasculares adversos importantes intrahospitalarios (MACE) en FA.ResultadosEntre los pacientes con FA, 503 (1,6%) tenían antecedentes de hipotiroidismo, 642 (2,0%) antecedentes de hipertiroidismo y 30.341 (96,4%) no tenía disfunción tiroidea. Durante esta hospitalización, 5.146 (16,3%) pacientes con FA sufrieron de MACE. La incidencia fue del 13,1% en hipotiroidismo, del 16,3% en eutiroidismo y del 19,0% en hipertiroidismo, en los que hubo una diferencia significativa entre 3 grupos (p=0,028). El análisis de regresión logística multivariable reveló que la historia de hipotiroidismo disminuyó, pero la historia de hipertiroidismo aumentó el riesgo de MACE intrahospitalario en pacientes con FA (relación de probabilidades ajustadas [OR]: 0,603; intervalo de confianza [IC] del 95%: 0,449-0,811; p=0,001 frente a OR ajustado 1,327; IC del 95%: 1,060-1,661; p=0,013). (AU)