Identification of biomarkers and potential therapeutic targets of kidney stone disease using bioinformatics.

PURPOSE: Kidney stone disease (KSD) is a common urological disease, but its pathogenesis remains unclear. In this study, we screened KSD-related hub genes using bioinformatic methods and predicted the related pathways and potential drug targets. METHODS: The GSE75542 and GSE18160 datasets in the Gene Expression Omnibus (GEO) were selected to identify common differentially expressed genes (DEGs). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify enriched pathways. Finally, we constructed a hub gene-miRNA network and drug-DEG interaction network. RESULTS: In total, 44 upregulated DEGs and 1 downregulated DEG were selected from the GEO datasets. Signaling pathways, such as leukocyte migration, chemokine activity, NF-κB, TNF, and IL-17, were identified in GO and KEGG. We identified 10 hub genes using Cytohubba. In addition, 21 miRNAs were predicted to regulate 4 or more hub genes, and 10 drugs targeted 2 or more DEGs. LCN2 expression was significantly different between the GEO datasets. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses showed that seven hub gene expressions in HK-2 cells with CaOx treatment were significantly higher than those in the control group. CONCLUSION: The 10 hub genes identified, especially LCN2, may be involved in kidney stone occurrence and development, and may provide new research targets for KSD diagnosis. Furthermore, KSD-related miRNAs may be targeted for the development of novel drugs for KSD treatment.

Biomimetic Hydrogel-Mediated Mechano-Immunometabolic Therapy for Inhibition of ccRCC Recurrence After Surgery.

The unique physical tumor microenvironment (TME) and aberrant immune metabolic status are two obstacles that must be overcome in cancer immunotherapy to improve clinical outcomes. Here, an in situ mechano-immunometabolic therapy involving the injection of a biomimetic hydrogel is presented with sequential release of the anti-fibrotic agent pirfenidone, which softens the stiff extracellular matrix, and small interfering RNA IDO1, which disrupts kynurenine-mediated immunosuppressive metabolic pathways, together with the multi-kinase inhibitor sorafenib, which induces immunogenic cell death. This combination synergistically augmented tumor immunogenicity and induced anti-tumor immunity. In mouse models of clear cell renal cell carcinoma, a single-dose peritumoral injection of a biomimetic hydrogel facilitated the perioperative TME toward a more immunostimulatory landscape, which prevented tumor relapse post-surgery and prolonged mouse survival. Additionally, the systemic anti-tumor surveillance effect induced by local treatment decreased lung metastasis by inhibiting epithelial-mesenchymal transition conversion. The versatile localized mechano-immunometabolic therapy can serve as a universal strategy for conferring efficient tumoricidal immunity in "cold" tumor postoperative interventions.