Background Anemia is one of the most common complications of sepsis. Sepsis-related anemia is associated mainly with inflammation. We aimed to observe the changes in the inflammatory anemia-associated parameters of patients with sepsis in the early stage of intensive care unit (ICU) admission and to evaluate their association with 28-day mortality. Methods A total of 198 patients with sepsis were divided into survivor ( n = 110) and non-survivor ( n = 88) groups on the basis of 28-day survival. Healthy volunteers ( n = 20) were enrolled as a control group. Plasma levels of iron, ferritin, erythropoietin (EPO), soluble transferrin receptor (sTfR), hepcidin, interleukin-6 (IL-6), hemoglobin and the red blood cell distribution width (RDW) were measured on days 1, 3 and 7 of ICU admission. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score was calculated. Results Patients with sepsis showed significant decreases in hemoglobin, plasma iron and sTfR/log ferritin and significant increases in plasma EPO, sTfR, hepcidin, ferritin and IL-6 on days 1, 3 and 7 of ICU admission compared with healthy volunteers. Hemoglobin was correlated negatively with plasma IL-6 and hepcidin. In patients with sepsis, non-survivors had significantly lower plasma iron, EPO and sTfR/log ferritin, but higher plasma hepcidin, ferritin and IL-6 than survivors on days 1, 3 and 7 of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality but to a varying extent. In particular, in predicting 28-day mortality, plasma hepcidin had an area under the receiver operating curve of 0.808 and 87.3% specificity, which was the highest among the inflammatory anemia-associated parameters tested. Conclusions Inflammatory anemia-associated parameters changed significantly in patients with sepsis in the first week of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality. Plasma hepcidin might have a superior predictive value, with high specificity, compared with other inflammatory anemia-associated parameters for 28-day mortality of sepsis patients in the ICU. Electronic supplementary material The online version of this article (10.1186/s13613-019-0542-7) contains supplementary material, which is available to authorized users.

Multidrug resistance among various bacterial strains is leading to worldwide resistance to a wide range of antibiotics. Combination therapy involving current antibiotics and other biological or chemical molecules represents an attractive novel strategy. In this study, we investigated the synergistic antibacterial activity of a series of Trp-containing antimicrobial peptides (AMPs) with four classes of traditional chemical antibiotics that are inactive against multidrug-resistant Staphylococcus epidermidis (MRSE) in vitro and in vivo. Among the antibiotics that we studied, penicillin, ampicillin and erythromycin showed a distinct synergistic effect in combination with all of the Trp-containing AMPs, represented by a fractional inhibitory concentration index (FICI) of <0.5. The antibacterial activities were noticeably improved, with 32-to 64-fold reductions in the MIC values for ampicillin and 16- to 32-fold reductions in the MIC values for erythromycin and penicillin. Tetracycline showed synergistic activity with only I1WL5W but additive activity with L11W, L12W, and I4WL5W. Ceftazidime exhibited additive activity with the Trp-containing peptides. In addition, the antibiotics in combination with the peptide significantly inhibited biofilm formation by MRSE 1208. A mechanistic study demonstrated that the Trp-containing peptides, especially I1WL5W and I4WL5W, which contain two tryptophan residues, disrupted bacterial inner and outer membranes, which promoted antibiotic delivery into the cytoplasm and access to cytoplasmic targets; however, L11W and L12W may have increased intracellular antibiotic concentrations by decreasing blaZ, tet(m) and msrA expression. Importantly, strong synergistic activity against the MRSE 1208 strain was observed for the combination of I1WL5W and penicillin in a mouse infection model. Thus, the combination of AMPs and traditional antibiotics could be a promising option for the prevention of acute and chronic infections caused by MRSE.

Background: Increasing evidence suggests that glutathione peroxidase 2 (GPX2) plays important roles in the tumorigenesis and progression of various human cancers, such as colorectal carcinomas and lung adenocarcinomas. However, the role of GPX2 in cervical cancer is unclear. In this study, we identified the role of GPX2 in cervical cancer tissues and cell lines. Materials and methods: The basal mRNA and protein expression of GPX2 in cervical cancer cells and a series of key molecules in the epithelial to mesenchymal transition (EMT) and WNT/β-catenin pathways were examined via real time fluorescence quantitative PCR (qRT-PCR) and Western blot assays. The biological phenotype of the cervical cancer cell lines was detected by the cloning formation and transwell assays, and intracellular reactive oxygen species (ROS) levels were detected by flow cytometry. Finally, the GPX2 expression level in 100 clinical cervical tissues was examined by immunohistochemistry. Results: We found that GPX2 was highly expressed in cervical cancer tissues compared to normal individuals and promoted the proliferation and metastasis of cervical cancer cells, and this promotion correlated with the activation of EMT and WNT/β-catenin signaling in vitro. GPX2 was determined to reduce apoptotic damage by reducing hydroperoxides. According to the characteristics and verification of GPX2, this series of phenotypes is clearly related to oxidative stress in cells. Furthermore, we verified that GPX2 was highly expressed in cervical cancer tissues and promoted the metastasis of cervical cancer. Conclusion: In summary, we found that GPX2 was highly expressed in cervical cancer cells and promoted the proliferation and metastasis of cervical cancer by affecting oxidative stress. Our study provides a new target for the clinical treatment of cervical cancer.

Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a series of Trp-containing peptides on the QS-regulated virulence and biofilm development of multidrug-resistant P. aeruginosa, as well as their synergistic antibacterial activity with three classes of traditional chemical antibiotics were investigated. The results showed that Trp-containing peptides at low concentrations reduced the production of QS-regulated virulence factors by downregulating the gene expression of both the las and rhl systems in the strain MRPA0108. Biofilm formation was inhibited in a concentration-dependent manner, which was associated with extracellular polysaccharide production inhibition by downregulating pelA, algD, and pslA transcription. These changes correlated with alterations in the extracellular production of pseudomonal virulence factors and swarming motility. In addition, the combination of Trp-containing peptides at low concentration with the antibiotics ceftazidime and piperacillin provided synergistic effects. Notably, L11W and L12W showed the highest synergy with ceftazidime and piperacillin. A mechanistic study demonstrated that the Trp-containing peptides, especially L12W, significantly decreased β-lactamase activity and expression of efflux pump genes OprM, MexX, and MexA, resulting in a reduction in antibiotic efflux from MRPA0108 cells and thus increasing the antibacterial activity of these antibiotics against MRPA0108.