Severe sepsis represents a common, expensive, and deadly health care issue with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis would help develop new therapeutic strategies against severe sepsis. In this study, we identified the crucial role of cell-free DNA (cfDNA) in the regulation of the Toll-like receptor 9–mediated proinflammatory pathway in severe sepsis progression. Hypothesizing that removing cfDNA would be beneficial for sepsis treatment, we used polyethylenimine (PEI) and synthesized PEI-functionalized, biodegradable mesoporous silica nanoparticles with different charge densities as cfDNA scavengers. These nucleic acid–binding nanoparticles (NABNs) showed superior performance compared with their nucleic acid–binding polymer counterparts on inhibition of cfDNA-induced inflammation and subsequent multiple organ injury caused by severe sepsis. Furthermore, NABNs exhibited enhanced accumulation and retention in the inflamed cecum, along with a more desirable in vivo safety profile. Together, our results revealed a key contribution of cfDNA in severe sepsis and shed a light on the development of NABN-based therapeutics for sepsis therapy, which currently remains intractable.
This cross-sectional study aimed at measuring the correlation and association between serum levels of cortisol, inflammatory cytokines, and depression and to measure the detection accuracy of serum levels of cortisol in serum samples. In total, 89 male participants were recruited into this study from June 15, 2017, to September 31, 2017. The Hamilton Depression Rating Scale, Beck Anxiety Inventory, and Pittsburgh Sleep Quality Index were used to investigate the mental health status of the participants. Serum concentrations of cortisol and inflammatory cytokines were determined. The serum cortisol concentration, anxiety level, and sleep quality were included in the final logistic regression model. Serum cortisol was able to accurately distinguish between patients with depression and those without depression. There was a significant positive correlation between serum cortisol levels and Hamilton Depression Rating Scale scores.
Our observation suggested that Berberine could inhibit the chemotherapy-induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation.
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