RESUMO
To investigate the correlation between nucleolar spindle-associated protein 1 (NUSAP1) and cancer immunotherapy across 33 different types of human cancers. We conducted an analysis of The Cancer Genome Atlas (TCGA) database to retrieve gene expression data and clinical characteristics for 33 different cancer types. The immunotherapy cohorts encompassed GSE67501, GSE78220, and IMvigor210. Relevant information was extracted from the gene expression repository. We assessed the prognostic significance of NUSAP1 by examining various clinical parameters. The single-sample gene-set enrichment analysis (ssGSEA) method was utilized to gauge NUSAP1 activity and to contrast NUSAP1 transcriptome and protein levels. We delved into the correlation between NUSAP1 and various immune processes and components to gain insights into NUSAP1's role. We also discussed coherent pathways associated with NUSAP1 signal transduction and its impact on immunotherapy biomarkers. To authenticate and validate the differential expression patterns of NUSAP1 in bladder tumor tissues versus normal bladder counterparts, we utilized Western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry (IHC) techniques. NUSAP1 exhibits overexpression across a spectrum of malignancies, and its expression levels correlate with overall survival (OS), disease-specific survival, and tumor stage in specific cancer types. Furthermore, NUSAP1 expression is linked to mutations, methylation patterns, and immunotherapy responses in human cancers. Meanwhile, our experiments, involving WB, RT-qPCR, and IHC, consistently demonstrated significantly higher NUSAP1 expression in bladder tumor tissues compared to normal controls. Our study underscores the potential of NUSAP1 as a promising prognostic indicator and immunotherapeutic target for a range of malignant tumors.
RESUMO
Tissue culture techniques have been routinely used for banana propagation and offered rapid production of planting materials with favorable genotypes and free of pathogenic microorganisms in the banana industry. Meanwhile, extensive scientific work suggests that micropropagated plantlets are more susceptible to Fusarium oxysporum f. sp. cubense (Foc), the deadly strain that causes Fusarium wilt of bananas than conventional planting material due to the loss of indigenous endophytes. In this study, an endophytic bacterium Bacillus velezensis EB1 was isolated and characterized. EB1 shows remarkable in vitro antagonistic activity against Foc with an inhibition rate of 75.43% and induces significant morphological and ultrastructural changes and alterations in the hyphae of Foc. Colony-forming unit (c.f.u.) counting and scanning electron microscopy (SEM) revealed that EB1 could colonize both the surface and inner tissues of banana tissue culture plantlets. Banana tissue culture plantlets of late rooting stage bioprimed with EB1 could efficiently ward off the invasive of Foc. The bio-priming effect could maintain in the acclimatized banana plants and significantly decrease the disease severity of Fusarium wilt and induce strong disease resistance by manipulating plant defense signaling pathways in a pot experiment. Our results provide the adaptability and potential of native endophyte EB1 in protecting plants from pathogens and infer that banana tissue culture plantlets bio-priming with endophytic microbiota could be a promising biological solution in the fight against the Fusarium wilt of banana.
RESUMO
As a typical triazole fungicide, prothioconazole (Pro) has been used extensively due to its broad spectrum and high efficiency. However, as a racemic mixture of two enantiomers (R-Pro and S-Pro), the enantiomer-specific outcomes on the bioactivity have not been fully elucidated. Here, we investigate how chirality affects the activity and mechanism of action of Pro enantiomers on Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), the notorious virulent strain causing Fusarium wilt of banana (FWB). The Pro enantiomers were evaluated in vivo and in vitro with the aid of three bioassay methods for their fungicidal activities against TR4 and the results suggested that the fungicidal activities of Pro enantiomers are stereoselective in a dose-dependent manner with R-Pro making a major contribution to the treatment outcomes. We found that R-Pro led to more severe morphological changes and impairment in membrane integrity than S-Pro. R-Pro also led to the increase of more MDA contents and the reduction of more SOD and CAT activities compared with the control and S-Pro groups. Furthermore, the expression of Cytochrome P450 14α-sterol demethylases (CYP51), the target for triazole fungicides, was significantly increased upon treatment with R-Pro rather than S-Pro, at both transcriptional and translational levels; so were the activities of the Cytochrome P450 enzymes. In addition, surface plasmon resonance (SPR) and molecular docking illuminated the stereoselective interactions between the Pro enantiomers and CYP51 of TR4 at the target site, and R-Pro showed a better binding affinity with CYP51 than S-Pro. These results suggested an enantioselective mechanism of Pro against TR4, which may rely on the enantioselective damages to the fungal cell membrane and the enantiospecific CYP51 binding affinity. Taken together, our study shed some light on the mechanisms underlying the differential activities of the Pro enantiomers against TR4 and demonstrated that Pro can be used as a potential candidate in the treatment of FWB.
