ABSTRACT
BACKGROUND: Sepsis is a major medical challenge. Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects, but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear. AIM: To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms. METHODS: Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue in animal studies. The histopathological changes of the ileal mucosa in different groups were observed under a microscope. Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced decrease in permeability. Immunofluorescence and Western blot assays were used to detect the levels of RANTES, inhibitor of nuclear factor kappa-B kinase ß (IKKß), phosphorylated IKKß (p-IKKß), inhibitor of nuclear factor kappa-B kinase α (IκBα), p65, and p-p65 proteins in different groups in vitro. RESULTS: In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol, magnolol inhibited the expression of proinflammatory cytokines, IL-1ß, IL-6, and TNF-α in a dose-dependent manner. In addition, magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats. Moreover, in vitro studies suggested that magnolol inhibited the increase of p65 nucleation, thereby markedly downregulating the production of the phosphorylated form of IKKß in LPS-treated Caco2 cells. Specifically, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells. CONCLUSION: Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways, thereby suppressing IL-1ß, IL-6, and TNF-α expression to alleviate the mucosal barrier dysfunction in sepsis.
ABSTRACT
PURPOSE: The objective of this study was to retrospectively research the clinical characteristics, pathogen distribution, prognosis of nosocomial bloodstream infection (nBSI), and the associated risk factors for nBSI. MATERIALS AND METHODS: The clinical and microbiological data of patients with nBSI were retrospectively studied. Patients were treated at the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Hangzhou, China) between January 2013 and December 2016. RESULTS: Our study spanned a four-year period and included 704 episodes of nBSI. The incidence rate was 4.11 per 1000 admissions. Of these cases, 96.7% were monomicrobial: gram-negative bacteria (56.4%), gram-positive bacteria (33.4%), and fungal (7%). Of all the Escherichia coli isolates, 41.5% were extended-spectrum ß-lactamase-producing (ESBL)-positive. Of the Klebsiella pneumoniae isolates, 50.9% were resistant to imipenem. Of the Staphylococcus aureus isolates, 42.1% were methicillin-resistant. The overall 28-day mortality rate in all patients with nBSI was 24.4%. Parenteral nutrition (PN) and sequential organ failure assessment (SOFA) scores (≥5) were closely related to the 28-day mortality rate of nBSI, while removal of venous catheters and appropriate empirical therapy were protective factors of 28-day mortality. CONCLUSIONS: Gram-negative bacteria predominantly developed in nBSI. Timely removal of venous catheters (catheter retention timeâ¯≥â¯7â¯days) and implementation of appropriate empirical therapy improved the nBSI outcomes.
