Lung cancer is a malignancy with high morbidity and mortality worldwide. More evidences indicated that gut microbiome plays an important role in the carcinogenesis and progression of cancers by metabolism, inflammation and immune response. However, the study about the characterizations of gut microbiome in lung cancer is limited. In this study, the fecal samples were collected from 16 healthy individuals and 30 lung cancer patients who were divided into 3 groups based on different tumor biomarkers (cytokeratin 19 fragment, neuron specific enolase and carcinoembryonic antigen, respectively) and were analyzed using 16S rRNA gene amplicon sequencing. Each lung cancer group has characterized gut microbial community and presents an elimination, low-density, and loss of bacterial diversity microbial ecosystem compared to that of the healthy control. The microbiome structures in family and genera levels are more complex and significantly varied from each group presenting more different and special pathogen microbiome such as Enterobacteriaceae, Streptococcus, Prevotella, etc and fewer probiotic genera including Blautia, Coprococcus, Bifidobacterium and Lachnospiraceae. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated decreased abundance of some dominant metabolism-related pathways in the lung cancer. This study explores for the first time the features of gut microbiome in lung cancer patients and may provide new insight into the pathogenesis of lung cancer system, with the implication that gut microbiota may serve as a microbial marker and contribute to the derived metabolites, development and differentiation in lung cancer system.

Pathological studies have shown an association between psoriasis and renal injury (RI), but the mechanism between RI and psoriasis was still unclear. This paper was designed to investigate the relationship and mechanism between psoriasis‐like inflammation and renal injury in BALB/C mice. Mice were topically smeared imiquimod followed by various analyses in skin lesions, urine protein, kidney/serum inflammatory cytokines, kidney function, podocyte membrane proteins, and toll‐like receptors/nuclear factor kappa‐b (TLR/NF‐κB) pathway‐associated proteins. Meanwhile, lipopolysaccharide (LPS) and dexamethasone (DEX) were intraperitoneally injected to promote and inhibit inflammation accompanied by imiquimod to elaborate the relevance between inflammatory levels and RI. In the model group, the Psoriasis Area and Severity Index (PASI) scores of scaly and erythema obviously increased (p < 0.01), creatinine and blood urea nitrogen significantly increased (p < 0.01), the positive area of hematoxylin‐eosin (HE) and periodic acid‐Schiff (PAS) staining in kidney increased (p < 0.01), malondialdehyde significantly increased with superoxide dismutase (SOD) decreased (p < 0.01), 24‐hour urine protein increased and the expressions of podocin and CD2 associate protein (CD2AP) decreased (p < 0.01), and kidney/serum inflammatory factors (IL‐17, IL‐1β, IL‐6, TNF‐α, and IL‐22) and TLR/NF‐κB‐related expression (TLR2, TLR4, MyD88, and NF‐κBp65) all increased (p < 0.01). The RI was aggravated with the TLR/NF‐κB related expression being upregulated by LPS (p < 0.05). On the contrary, the RI was alleviated by DEX (p < 0.05). Our data showed that psoriasis‐like inflammation damaged the renal function via the TLR/NF‐κB signal pathway. Inhibiting TLR/NF‐κB‐related protein expression may be effective for the treatment of RI caused by psoriasis.

The opportunistic pathogen Aspergillus fumigatus has developed worldwide resistance to azoles largely through mutations in cytochromeP450 enzyme Cyp51. In this study, we indicated that in vitro azole situation results in emergence of azole-resistant mutations. There are previously identified azole-resistant cyp51A mutations (M220K, M220I, M220R, G54E and G54W mutations) and we successfully identified in this study two new mutations (N248K/V436A, Y433N substitution) conferring azole resistance among 18 independent stable azole-resistant isolates. The Galleria mellonella model of A. fumigatus infection experiment verified that Cyp51A mutations N248K/V436A and Y433N reduce efficacy of azole therapy. In addition, a predicted Cyp51A 3D structural model suggested that Y433N mutation causes the reduced affinities between drug target Cyp51A and azole antifungals. This study suggests that drug selection pressure make it possible to isolate unidentified cyp51A mutations conferring azole resistance in A. fumigatus.

The incidence of aspergillosis continues to rise sharply, while the progress made in expanding the antifungal drug arsenal remains extremely slow, indicating an urgent need for new strategies. Previous studies have shown that the calcium signaling pathway, which is evolutionarily conserved in mammals and fungi, is involved in regulating the tolerance of azoles in fungi. In this study, we performed a preliminary screening among various combinations of different clinical calcium channel blockers and different antifungal drugs. We found that the combination of itraconazole and verapamil showed the best synergistic effect against Aspergillus fumigatus. Thereafter, using the checkboard assays we observed synergistic effects of the combination treatment against most of the A. fumigatus strains tested, including itraconazole-sensitive and itraconazole-resistant strains, with a fractional inhibitory concentration index (FICI) < 0.5. Furthermore, we showed that verapamil strongly decreased the cytosolic calcium transients following itraconazole stimulation by an aequorin-mediated method. Moreover, verapamil influenced the efflux of rhodamine 6G, an azole mimic substance. An ergosterol assay revealed that verapamil alone had no effect on ergosterol biosynthesis, but the combination of itraconazole and verapamil treatment decreased the ergosterol level. Further murine assays were performed using a luciferase-probed bioluminescence imaging method. Drug combination therapy reduced lung burden and improved survival rate. In conclusion, verapamil is a promising candidate to enhance the antifungal activity of itraconazole against A. fumigatus. In addition, our study suggests the effectiveness of an emerging approach based on bioluminescence imaging in monitoring the efficacy of drug combination therapy for invasive aspergillosis.