BACKGROUND:Ferroptosis and pyroptosis may play a role in the development of postmenopausal osteoporosis.There may be relevant biomarkers for the diagnosis of postmenopausal osteoporosis. OBJECTIVE:To search for the key genes related to ferroptosis and pyroptosis in postmenopausal osteoporosis using bioinformatics so as to further elucidate their biological mechanisms. METHODS:The data sets GSE56815 and GSE7429 of postmenopausal osteoporosis were downloaded from the GEO database,the national comprehensive gene expression database of the United States,and the two data sets were preprocessed.The differential expression analysis of the data was carried out by the limma package of R software,and the enrichment analysis was performed by DIVID and KOBAS.The protein-protein interaction network was mapped by STRING and Cytoscape,the Hub gene was selected by CytoHubba,and the key genes were screened by the ferroptosis database and pyroptosis database.The CIBERSORT package was used to determine the immune infiltration of postmenopausal osteoporosis samples and to analyze the correlation between key genes and immune cells RESULTS AND CONCLUSION:A total of 30 differential genes of postmenopausal osteoporosis were screened in the experimental samples,of which 9 genes were up-regulated and 21 genes were down-regulated.The enrichment of GO and KEGG pathways showed that the differences were mainly in"serine-type endopeptidase activity,""innate immune response,""special particle lumen,"and"renin secretion."The protein-protein interaction network showed the correlation of differential genes and the top 10 Hub genes with"Degree"value were selected using CytoHubba.Hub gene was intersected with the FerrDb database and cell pyroptosis dataset to obtain key genes ELANE and LCN2.Receiver operating characteristic curve and box diagram showed that the expression of ELANE and LCN2 in serum samples of postmenopausal osteoporosis was significantly lower than that in normal samples,indicating a good diagnostic value.Immune infiltration analysis showed that ELANE may be related to memory resting CD4+ T cells,M0 and M2 macrophages.LCN2 may be related to M0 macrophages.

Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy. Among vascular coagulation agents, the extracellular domain of coagulation-inducing protein tissue factor, truncated tissue factor (tTF), is the most widely used. Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation, free tTF cannot be used for cancer treatment on its own but must be combined with other moieties. We here developed a novel, tumor-specific tTF delivery system through coupling tTF with the DNA aptamer, AS1411, which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells. Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors, thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects. This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.