RESUMO
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer associated with poor prognosis, and accounts for the majority of RCC-related deaths. The lack of comprehensive diagnostic and prognostic biomarkers has limited further understanding of the pathophysiology of ccRCC. Super-enhancers (SEs) are congregated enhancer clusters that have a key role in tumor processes such as epithelial-mesenchymal transition, metabolic reprogramming, immune escape and resistance to apoptosis. RCC may also be immunogenic and sensitive to immunotherapy. In the present study, an Arraystar human SE-long non-coding RNA (lncRNA) microarray was first employed to profile the differentially expressed SE-lncRNAs and mRNAs in 5 paired ccRCC and peritumoral tissues and to identify SE-related genes. The overlap of these genes with immune genes was then determined to identify SE-related immune genes. A model for predicting clinical prognosis and response to immunotherapy was built following the comprehensive analysis of a ccRCC gene expression dataset from The Cancer Genome Atlas (TCGA) database. The patients from TCGA were divided into high- and low-risk groups based on the median score derived from the risk model, and the Kaplan-Meier survival analysis showed that the low-risk group had a higher survival probability. In addition, according to the receiver operating characteristic curve analysis, the risk model had more advantages than other clinical factors in predicting the overall survival (OS) rate of patients with ccRCC. Using this model, it was demonstrated that the high-risk group had a more robust immune response. Furthermore, 61 potential drugs with half-maximal inhibitory concentration values that differed significantly between the two patient groups were screened to investigate potential drug treatment of ccRCC. In summary, the present study provided a novel index for predicting the survival probability of patients with ccRCC and may provide some insights into the mechanisms through which SE-related immune genes influence the diagnosis, prognosis and potential treatment drugs of ccRCC.
RESUMO
Bacterial infections pose a global concern due to high fatality rates, particularly with the rise of drug-resistant bacteria and biofilm formation. There is an urgent need for innovative strategies to combat this issue. A study on chemodynamic therapy (CDT) using nanozymes in conjunction with photothermal therapy (PTT) has displayed potential in addressing drug-resistant bacterial infections. However, the effectiveness of this combined approach is limited by inadequate light absorption. This work suggests the NiOx nanoparticles enriched with oxygen vacancies enhance CDT and PTT to overcome this challenge. The presence of oxygen vacancies in NiOx can reduce the energy gap between its valence band and conduction band, facilitating oxygen adsorption. NiOx has exhibited notable antibacterial properties and complete eradication of biofilms in both laboratory and animal trials. In animal abscess models, NiOx demonstrated antibacterial and anti-inflammatory effects in the initial stages, while also promoting wound healing and tissue regeneration by influencing immune factors and encouraging collagen deposition and neovascularization. With positive biosafety and biocompatibility profiles, the oxygen vacancy-enhanced CDT and PTT therapy proposed in this article hold promise for effective sterilization, deep biofilm removal, and treatment of infections caused by drug-resistant bacteria. STATEMENT OF SIGNIFICANCE: This study constructs oxygen vacancies NiOx nanoparticles (NiOx NPs) to improve the efficacy of photothermal therapy and chemodynamic therapy. The presence of oxygen vacancies in NiOx NPs helps bridge the energy gap between its valence band and conduction band, facilitating oxygen adsorption and improving catalytic efficiency. In both in vivo and in vitro antibacterial experiments, NiOx NPs demonstrate effective antibacterial and anti-inflammatory properties. Furthermore, it aids in wound healing and tissue regeneration by modulating immune factors, collagen deposition, and angiogenesis. This approach presents a promising collaborative strategy for utilizing nickel-based defective nanomaterials in combating deep drug-resistant bacterial infections.