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IntroductionPsoriasis is a chronic inflammatory disease of the skin. A few studies have shown that psoriasis is an immune-mediated disease in which multiple immune cells play crucial roles. However, the association between circulating immune cells and psoriasis remains elusive.MethodsTo explore the role of circulating immune cells in psoriasis, 361,322 individuals from the UK Biobank (UKB) and 3,971 patients with psoriasis from China were included to investigate the association between white blood cells and psoriasis via an observational study. Genome-wide association studies (GWAS) and Mendelian randomization (MR) were used to evaluate the causal relationship between circulating leukocytes and psoriasis.ResultsThe risk of psoriasis increased with high levels of monocytes, neutrophils, and eosinophils (relative risks and 95% confidence intervals, respectively: 1.430 (1.291–1.584) for monocytes, 1.527 (1.379–1.692) for neutrophils, and 1.417 (1.294–1.551) for eosinophils). Upon further MR analysis, eosinophils showed a definite causal relationship with psoriasis (odds ratio of inverse-variance weighted: 1.386, 95% confidence intervals: 1.092–1.759) and a positive correlation with the psoriasis area and severity index (PASI) score (P = 6.6 × 10-5). The roles of the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) in psoriasis were also assessed. More than 20,000 genetic variations associated with NLR, PLR, and LMR were discovered in a GWAS analysis using the UKB data. Following adjustment for covariates in the observational study, NLR and PLR were shown to be risk factors for psoriasis, whereas LMR was a protective factor. MR results indicated that there was no causal relationship between these three indicators and psoriasis; however, NLR, PLR, and LMR correlated with the PASI score (NLR: rho = 0.244, P = 2.1 × 10-21; PLR: rho = 0.113, P = 1.4 × 10-5; LMR: rho = -0.242, P = 3.5×10-21).DiscussionOur findings revealed an important association between circulating leukocytes and psoriasis, which is instructive for the clinical practice of psoriasis treatment.

Immunotherapy has demonstrated the potential to cure melanoma, while the current response rate is still unsatisfactory in clinics. Extensive evidence indicates the correlation between the efficacy and pre-existing T-cell in tumors, whereas the baseline T-cell infiltration is lacking in low-response melanoma patients. Herein, we demonstrated the critical contribution of dendritic cells (DCs) on melanoma survival and baseline T-cell level, as well as the efficacy of immunotherapy. Capitalized on this fact, we developed a photothermal nano-vaccine to simultaneously promote tumor antigens presentation and DCs infiltration for enhanced immunotherapy. The nano-vaccine was composed of polyserotonin (PST) core and tannic acid (TA)/Mn2+ coordination-based metal-organic-framework (MOF) shell for β-catenin silencing DNAzyme loading, which was further integrated into dissolving microneedles to allow noninvasive and transdermal administration at melanoma skin. The nano-vaccine could rapidly penetrate skin upon microneedles insertion and exert a synergistically amplified photothermal effect to induce immunogenic cell death (ICD). The MOF shell then dissociated and released Mn2+ as a cofactor to self-activate DNAzyme for β-catenin suppression, which in turn caused a persistent CCL4 excretion to promote the infiltration of DCs into the tumor. Meanwhile, the liberated PST core could effectively capture and facilitate tumor antigens presentation to DCs. As a result, potent antitumor efficacies were achieved for both primary and distal tumors without any extra treatment, indicating the great promise of such a nano-vaccine for on-demand personalized immunotherapy of melanoma.

Staphylococcus aureus is a common commensal of humans, and its translocation from gastrointestine to peripheral organs and tissues could cause severe diseases and complications. This study focuses on the screening and characterization of Lactobacillus strains with significant inhibitory effect on the translocation of S. aureus through Caco-2 monolayers. First, strains with strong affinity for mucin and Caco-2 cells were obtained, via microtiter plate assay and adhesion assay, respectively. Obtained bacteria were further tested for their inhibitory effects on the growth of S. aureus by well diffusion assay. Subsequently, two strains preincubated with Caco-2 monolayers were found to inhibit the translocation of S. aureus CMCC26003 by 80.95 and 43.96%, respectively, via the transcellular translocation assay. These two strains were then identified to be Lactobacillus fermentum NCU3087 and L. fermentum NCU3088. Second, the mechanism of inhibition was investigated by analyzing the relative concentration of tight junction proteins and proinflammatory cytokines of Caco-2 cells, by Western blot and enzyme-linked immunosorbent assay, respectively. Results showed that both NCU3087 and NCU3088 significantly attenuated the degradation of occludin, claudin-1, ZO-1, and JAM-1 and suppressed the secretion of interleukin 6 and tumor necrosis factor-α induced by S. aureus, to different extent. Moreover, two Lactobacillus strains could barely translocate the Caco-2 monolayers, had no hemolytic activity, displayed strong resistance to gastrointestinal fluids, and were sensitive or moderate sensitive to nine clinically relevant antibiotics. Collectively, this study identified two Lactobacillus strains with significant inhibitory effect on the translocation of S. aureus, and their safeness for application was evaluated, thereby providing potential solutions for prevention of S. aureus and prophylaxis of related diseases.