Integrated Bioinformatics Analysis Reveals Diagnostic Biomarkers and Immune Cell Infiltration Characteristics of Solar Lentigines.

Background: Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers. Objective: The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features. Methods: In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model's classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs. Results: The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells. Conclusion: Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.

Antifungal Activity and Potential Action Mechanism of Allicin against Trichosporon asahii.

Trichosporon asahii is an emerging opportunistic pathogen that causes potentially fatal disseminated trichosporonosis. The global prevalence of coronavirus disease 2019 (COVID-19) poses an increasing fungal infection burden caused by T. asahii. Allicin is the main biologically active component with broad-spectrum antimicrobial activity in garlic. In this study, we performed an in-depth analysis of the antifungal characteristics of allicin against T. asahii based on physiological, cytological, and transcriptomic assessments. In vitro, allicin inhibited the growth of T. asahii planktonic cells and biofilm cells significantly. In vivo, allicin improved the mean survival time of mice with systemic trichosporonosis and reduced tissue fungal burden. Electron microscopy observations clearly demonstrated damage to T. asahii cell morphology and ultrastructure caused by allicin. Furthermore, allicin increased intracellular reactive oxygen species (ROS) accumulation, leading to oxidative stress damage in T. asahii cells. Transcriptome analysis showed that allicin treatment disturbed the biosynthesis of cell membrane and cell wall, glucose catabolism, and oxidative stress. The overexpression of multiple antioxidant enzymes and transporters may also place an additional burden on cells, causing them to collapse. Our findings shed new light on the potential of allicin as an alternative treatment strategy for trichosporonosis. IMPORTANCE Systemic infection caused by T. asahii has recently been recognized as an important cause of mortality in hospitalized COVID-19 patients. Invasive trichosporonosis remains a significant challenge for clinicians, due to the limited therapeutic options. The present work suggests that allicin holds great potential as a therapeutic candidate for T. asahii infection. Allicin demonstrated potent in vitro antifungal activity and potential in vivo protective effects. In addition, transcriptome sequencing provided valuable insights into the antifungal effects of allicin.

Pathogenicity of phospholipase B1 of Trichosporon asahii in immunosuppressed mice.

BACKGROUND: Trichosporon asahii is an opportunistic pathogenic yeast-like fungus. Phospholipase B1 (PLB1) is an important virulence factor of pathogenic fungi such as Candida albicans and Cryptococcus neoformans, and there are few studies on the role of PLB1 in the pathogenicity of T. asahii. OBJECTIVES: To investigate the role of PLB1 in the pathogenicity of T. asahii. METHODS: A strain with low secretion of PLB1 (4848) was screened, a PLB1 overexpression strain (PLB1OX ) was constructed, and the differences in histopathology, fungal load of organ, survival time of mice, the levels of IL-6, IL-10, TNF-α, and GM-GSF in the serum and organs caused by the two strains were compared. RESULTS: Histopathology showed that spores and hyphae were observed in both groups, and PLB1OX led to more fungal invasion. The fungal loads in the kidney, lung, spleen and liver in the PLB1OX group were significantly higher than those in the 4848 group, and the survival time of mice was significantly lower than that in the 4848 group. The levels of TNF-α in the serum, liver, spleen, lung and kidney of the PLB1OX group were lower than those of the 4848 group, while the level of IL-10 in the serum was higher than that of the 4848 group. CONCLUSIONS: These results suggest that PLB1 can enhance the invasive function of T. asahii and affect the secretion of TNF-α and IL-10 which may affect the host antifungal immune response, providing evidence that PLB1 plays a role in the pathogenic infection of T. asahii.