RESUMO
Inflammatory responses are associated with the development of vascular dementia (VaD). Circulating cytokines modulate the inflammatory response and are important for the immune system. To further elucidate the role of the immune system in VaD, we used Mendelian randomization (MR) to comprehensively and bi-directionally assess the role of circulating cytokines in VaD. Using state-of-the-art genome-wide association studies, we primarily assessed whether different genetic levels of 41 circulating cytokines affect the risk of developing VaD and, in turn, whether the genetic risk of VaD affects these circulating cytokines. We used inverse variance weighting (IVW) and several other MR methods to assess the bidirectional causality between circulating cytokines and VaD, and performed sensitivity analyses. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was inversely associated with VaD risk [odds ratio (OR): 0.74, 95 % confidence interval (CI): 0.60-0.92, P = 0.007, 0.007]. VaD was associated with seven circulating cytokines: macrophage inflammatory protein 1b (MIP-1 beta) [OR: 1.05, 95 % CI: 1.01-1.08, P = 0.009], Interleukin-12p70 (IL-12) [OR: 1.04, 95 % CI: 1.00-1.08, P = 0.047], Interleukin-17 (IL-17) [OR: 1.04, 95 % CI: 1.00-1.07, P = 0.038], Interleukin-7 (IL-7) [OR: 1.07, 95 % CI: 1.02-1.12, P = 0.009], Interferon gamma (IFN-γ) [OR: 1.03, 95 % CI: 1.00-1.07, P = 0.046], Granulocyte-colony stimulating factor (GCSF) [OR: 1.06, 95 % CI: 1.02-1.09, P = 0.001], Fibroblast growth factor (FGF) [P = 0.001], and Fibroblast growth factor (FGF) [P = 0.001]. Fibroblast growth factor basic (FGF-Basic) [OR: 1.04, 95 % CI: 1.01-1.08, P = 0.02] were positively correlated. Circulating cytokines are associated with VaD, and further studies are needed to determine whether they are effective targets for intervention to prevent or treat VaD.
Assuntos
Citocinas , Demência Vascular , Humanos , Demência Vascular/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Fatores de Crescimento de FibroblastosRESUMO
Cholesterol is an indispensable component of most liposomes, heavily influencing their physical and surface properties. In this study, cholesterol in non-PEGylated liposomes was replaced by its analog, asiatic acid (AA), to generate liposomes with an alternative composition. These AA liposomes are generally smaller and more rigid than conventional liposomes, circulate longer in the body, and accumulate more in primary tumors and lung metastases in vivo. On the other hand, as an active ingredient, AA can decrease TGF-ß secretion to inhibit the epithelial-mesenchymal transition (EMT) process, increase the sensitivity of tumor cells to doxorubicin (DOX), and synergize with DOX to enhance the immune response, thus improving their antitumor and anti-metastasis efficiency. Based on this rationale, DOX-loaded AA liposomes were fabricated and tested against triple-negative breast cancer (TNBC). Results showed that compared with conventional liposomes, the DOX-AALip provided approximately 28.4% higher tumor volume reduction with almost no metastatic nodules in the mouse model. Our data demonstrate that AA liposomes are safe, simple, and efficient, and thus in many situations may be used instead of conventional liposomes, having good potential for further clinical translational development.
Assuntos
Colesterol , Doxorrubicina/análogos & derivados , Lipossomos , Triterpenos Pentacíclicos , Camundongos , Animais , Linhagem Celular Tumoral , PolietilenoglicóisRESUMO
ABSTRACT Objective: Based on the evaluation method with fuzzy integrals, this paper analyzes the results of physical health tests of college students. Methods: Principal component analysis was used to extract the psychological factors. The evaluation model was organized into three levels to evaluate the physical health of college students. Results: The physical health status of University Q students is below average. Most of the students' physical examination results are concentrated in the passing areas, and few students have an excellent to good ratio. Conclusion: The fitness assessment model of university students, based on an assessment with fuzzy integrals, has certain generalizability and applicability. The established index system and the comprehensive evaluation model are suitable for thoroughly evaluating each student and comprehensive fitness evaluation of all boys and girls in a class or college. Level of evidence II; Therapeutic studies - investigation of treatment results.
RESUMO Objetivo: Com base no método de avaliação com integrais fuzzy, este documento analisa os resultados dos testes de saúde física dos estudantes universitários. Métodos: Foi utilizada a análise de componentes principais para extrair os fatores psicológicos. O modelo de avaliação foi organizado em três níveis para avaliar a saúde física dos estudantes universitários. Resultados: O estado de saúde física dos estudantes da Universidade Q está abaixo da média. A maioria dos resultados dos exames físicos dos estudantes está concentrada nas áreas de aprovação, e poucos estudantes têm uma proporção excelente e boa. Conclusão: O modelo de avaliação da aptidão física dos estudantes universitários, baseado em uma avaliação com integrais fuzzy, tem certa generalização e aplicabilidade. O sistema de índice estabelecido e o modelo de avaliação abrangente não só são adequados para avaliação abrangente de cada estudante, mas também para avaliação abrangente da aptidão física de todos os meninos e meninas de uma classe ou faculdade. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.
Resumen Objetivo: Basándose en el método de evaluación con integrales difusas, este artículo analiza los resultados de las pruebas de salud física de los estudiantes universitarios. Métodos: Se utilizó el análisis de componentes principales para extraer los factores psicológicos. El modelo de evaluación se organizó en tres niveles para evaluar la salud física de los estudiantes universitarios. Resultados: El estado de salud física de los estudiantes de la Universidad Q está por debajo de la media. La mayoría de los resultados de los exámenes físicos de los estudiantes se concentran en las zonas de aprobado, y son pocos los que tienen una proporción excelente y buena. Conclusión: El modelo de evaluación de la aptitud física de los estudiantes universitarios basado en una evaluación con integrales difusas tiene cierta generalizabilidad y aplicabilidad. El sistema de índices establecido y el modelo de evaluación integral no sólo son adecuados para la evaluación integral de cada estudiante, sino también para la evaluación integral de la aptitud de todos los chicos y chicas de una clase o colegio. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.