This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Inappropriate inflammation responses contribute to mortality during sepsis. Through Toll-like receptors (TLRs), reactive oxygen species (ROS) produced by NADPH oxidase could modulate the inflammation responses. Parkinson disease (autosomal recessive, early onset) 7 (Park7) has a cytoprotective role by eliminating ROS. However, whether Park7 could modulate inflammation responses and mortality in sepsis is unclear. Here, we show that, compared with wild-type mice, Park7 −/− mice had significantly increased mortality and bacterial burdens in sepsis model along with markedly decreased systemic and local inflammation, and drastically impaired macrophage phagocytosis and bacterial killing abilities. Surprisingly, LPS and phorbol-12-myristate-13-acetate stimulation failed to induce ROS and proinflammatory cytokine production in Park7 −/− macrophages and Park7-deficient RAW264.7 cells. Through its C-terminus, Park7 binds to p47 phox , a subunit of the NADPH oxidase, to promote NADPH oxidase-dependent production of ROS. Restoration of Park7 expression rescues ROS production and improves survival in LPS-induced sepsis. Together, our study shows that Park7 has a protective role against sepsis by controlling macrophage activation, NA-DPH oxidase activation and inflammation responses.

Stress ulceration is a common complication in critically ill patients and can result in significant upper gastrointestinal bleeding associated with a high morbidity and mortality. At present, little is known of the molecular mechanisms underlying the incidence of this type of gastric damage. In the present study, we investigated the temporal activation of the redox-sensitive p38 signaling transduction cascade and its roles in a well-defined experimental model of cold immobilization stress-induced gastric ulceration. Exposure of Sprague-Dawley rats to 6 h of cold immobilization stress led to a rapid activation of p38 in the gastric mucosa at as early as 15 min after stress, and this activation was maximal after 1.5 h of stress and still persisted until the end of stress. Selectively blocking p38 by pretreatment with SB 239063, a potent and selective p38 inhibitor, suppressed the stress-promoted TNF-α, IL-1β, and CINC-1 production and then prevented the subsequent neutrophil infiltration, gastric mucosal epithelial necrosis and apoptosis, and the ulcerative lesions formation. Prior administration of the free radical scavengers, tempol and N-acetyl-l-cysteine, abolished the stress induction of p38 activation and the resulting mucosal inflammation and gastric injury. These results demonstrate that reactive oxygen species-mediated p38 activation plays an essential role in the pathogenesis of stress-induced gastric inflammatory damage in the rat model of cold immobilization stress. Our findings suggested that inhibition of p38 activation might be a potential strategy for the prophylaxis and treatment of stress ulceration.

As important lactic acid bacteria, Enterococcus species are widely used in the production of fermented food. However, as some strains of Enterococcus are opportunistic pathogens, their safety has not been generally accepted. In recent years, a large number of new species have been described and classified within the genus Enterococcus, so a better understanding of the genetic relationships and evolution of Enterococcus species is needed. In this study, the genomes of 29 type strains of Enterococcus species were sequenced. In combination with eight complete genome sequences from the Genbank database, the whole genomes of 37 strains of Enterococcus were comparatively analyzed. The average length of Enterococcus genomes was 3.20Mb and the average GC content was 37.99%. The core- and pan- genomes were defined based on the genomes of the 37 strains of Enterococcus. The core-genome contained 605 genes, a large proportion of which were associated with carbohydrate metabolism, protein metabolism, DNA and RNA metabolism. The phylogenetic tree showed that habitat is very important in the evolution of Enterococcus. The genetic relationships were closer in strains that come from similar habitats. According to the topology of the time tree, we found that humans and mammals may be the original hosts of Enterococcus, and then species from humans and mammals made a host-shift to plants, birds, food and other environments. However, it was just an evolutionary scenario, and more data and efforts were needed to prove this postulation. The comparative genomic analysis provided a snapshot of the evolution and genetic diversity of the genus Enterococcus, which paves the way for follow-up studies on its taxonomy and functional genomics.

No abstract

The corrosion behavior at open circuit potential (OCP) and the discharge performance under impressed anodic current of Mg-5Li-3Al-1Zn (LAZ531) alloy sheets with different rolling reductions are investigated using hydrogen evolution, potentiodynamic polarization, electrochemical impedance spectroscopy, and galvanostatic discharge measurements. The results show that rolling increases the corrosion resistance and strengthens the discharge ability of LAZ531 alloy, which is attributed to the increased density of twins and the change of grain orientation. Of those, the LAZ531 alloy with 20% rolling reduction (LAZ531%-20%) has high and steady discharge voltage at small current density for long time, with the values of 1.490 V at 2.5 mA cm −2 and 1.411 V at 10 mA cm −2 . The grain boundaries and twins play the same roles on the corrosion and discharge processes, which are attacked preferentially than the grain interiors and accelerate the dissolution of LAZ531 alloy.

No abstract

Chronic liver inflammation and injuries play a critical role in development of hepatocellular carcinoma (HCC). Parkinson disease (autosomal recessive, early onset) 7, encoding PARK7 protein (also called DJ-1), plays important roles in many carcinogenesis processes and is essential in modulating inflammation. However, whether DJ-1 is involved in HCC development remains largely unknown. To determine the effect of DJ-1 on HCC development, we accessed the correlation of hepatic DJ-1 expression with overall survival (OS) and TNM stage in 96 HCC patients and found a significant inverse correlation between DJ-1 expression and OS. By adopting a classic diethylnitrosamine (DEN)-induced murine HCC model, DJ-1 knockout (KO) mice displayed reduced tumorigenesis and cell proliferation, accompanied by decreased hepatic inflammation and IL-6/STAT3 activation. Furthermore, after an acute DEN challenge, DJ-1 KO mice showed significant decreases in liver injury, hepatocyte proliferation and DNA damage. In a human HCC cell line (MHCC-97L), cancer cell proliferation was induced by overexpression of DJ-1 and is related to oncogenic signaling of MAPKs and AKT. Induction of DJ-1 may serve as a novel regulator for HCC cell proliferation and HCC development possibly through enhanced MAPK signaling and inflammation.