RESUMEN
Thickening of the ligamentum flavum is the main factor in the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported factors related to ligamentum flavum thickening, its etiology has not been clarified. Furthermore, it is often difficult to set proper controls to investigate the pathologies of thickening due to differences in patient characteristics, such as age, sex, obesity, and comorbidities. This study aimed to elucidate the pathologies of ligamentum flavum thickening by comparing the dural and dorsal sides of the thickened ligamentum flavum in patients with LSCS. Ligamentum flavum samples were collected from 19 patients with LSCS. The samples were divided into the dural and dorsal sides. The dural side was used as a control to assess the pathologies occurring on the dorsal side. Elastic Masson staining was used to assess the elastic fibres. Gene expression levels were comprehensively assessed using quantitative reverse transcription polymerase chain reaction and DNA microarray analyses. Gene ontology analysis was used to identify biological processes associated with differentially expressed genes. The elastic fibres were significantly decreased on the dorsal side of the thickened ligamentum flavum. Genes related to fibrosis, inflammation, tissue repair, remodeling, and chondrometaplasia, such as COL1A2, COL3A1, COL5A1, TGFB1, VEGFA, TNFA, MMP2, COL10A1, and ADAMTS4, were highly expressed on the dorsal side of the thickened ligamentum flavum. The biological processes occurring on the dorsal side of the thickened ligamentum flavum were extracellular matrix organization, cell adhesion, extracellular matrix disassembly, and proteolysis.These are considered important pathologies of ligamentum flavum thickening.
Asunto(s)
Duramadre , Perfilación de la Expresión Génica , Ligamento Amarillo , Vértebras Lumbares , Estenosis Espinal , Humanos , Ligamento Amarillo/patología , Ligamento Amarillo/metabolismo , Estenosis Espinal/genética , Estenosis Espinal/patología , Masculino , Femenino , Vértebras Lumbares/patología , Anciano , Duramadre/patología , Duramadre/metabolismo , Regulación de la Expresión Génica , Persona de Mediana Edad , Ontología de Genes , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
Background: Considering the diversity of tumors, it is of great significance to develop a simple, effective, and low-cost method to prepare personalized cancer vaccines. Methods: In this study, a facile one-pot synthetic route was developed to prepare cancer vaccines using model antigen or autologous tumor antigens based on the coordination interaction between Fe3+ ions and endogenous fumarate ligands. Results: Herein, Fe-based metal organic framework can effectively encapsulate tumor antigens with high loading efficiency more than 80%, and act as both delivery system and adjuvants for tumor antigens. By adjusting the synthesis parameters, the obtained cancer vaccines are easily tailored from microscale rod-like morphology with lengths of about 0.8 µm (OVA-ML) to nanoscale morphology with sizes of about 50~80 nm (OVA-MS). When cocultured with antigen-presenting cells, nanoscale cancer vaccines more effectively enhance antigen uptake and Th1 cytokine secretion than microscale ones. Nanoscale cancer vaccines (OVA-MS, dLLC-MS) more effectively enhance lymph node targeting and cross-presentation of tumor antigens, mount antitumor immunity, and inhibit the growth of established tumor in tumor-bearing mice, compared with microscale cancer vaccines (OVA-ML, dLLC-ML) and free tumor antigens. Conclusions: Our work paves the ways for a facile, rapid, and low-cost preparation approach for personalized cancer vaccines.