Accumulating evidence indicates the occurrence and development of diabetic complications relates to not only constant high plasma glucose, but also glucose fluctuations which affect various kinds of molecular mechanisms in various target cells and tissues. In this review, we detail reactive oxygen species and their potentially damaging effects upon glucose fluctuations and resultant downstream regulation of protein signaling pathways, including protein kinase C, protein kinase B, nuclear factor-κB, and the mitogen-activated protein kinase signaling pathway. A deeper understanding of glucose-fluctuation-related molecular mechanisms in the development of diabetic complications may enable more potential target therapies in future.

BACKGROUND AND PURPOSELipopolysaccharides (LPS) and oligodeoxynucleotides containing CpG motifs (CpG DNA) are important pathogenic molecules for the induction of sepsis, and thus are drug targets for sepsis treatment. The present drugs for treating sepsis act only against either LPS or CpG DNA. Hence, they are not particularly efficient at combating sepsis as the latter two molecules usually cooperate during sepsis. In this study, a natural alkaloid compound kukoamine B (KB) is presented as a potent dual inhibitor for both LPS and CpG DNA. EXPERIMENTAL APPROACHThe affinities of KB for LPS and CpG DNA were assessed using biosensor technology. Direct interaction of KB with LPS and CpG DNA were evaluated using neutralization assays. Selective inhibitory activities of KB on pro-inflammatory signal transduction and cytokine expression induced by LPS and CpG DNA were analysed by cellular assays. Protective effects of KB in a sepsis model in mice were elucidated by determining survival and circulatory LPS and tumour necrosis factor-alpha (TNF-a) concentrations. KEY RESULTSKB had high affinities for LPS and CpG DNA. It neutralized LPS and CpG DNA and prevented them from interacting with mouse macrophages. KB selectively inhibited LPS-and CpG DNA-induced signal transduction and expression of pro-inflammatory mediators without interfering with signal pathways or cell viability in macrophages. KB protected mice challenged with heat-killed Escherichia coli, and reduced the circulatory levels of LPS and TNF-a. CONCLUSIONS AND IMPLICATIONSThis is the first report of a novel dual inhibitor of LPS and CpG DNA. KB is worthy of further investigation as a potential candidate to treat sepsis. Abbreviations

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The aim of this study was to investigate lipolysis and lipid oxidation of stored eggs at different temperatures (4 and 22°C) by evaluating the changes in physicochemical index, lipid profiles, enzymatic activity, and oxidative index. The results showed that the changes in physicochemical index were more significant at 22°C than at 4°C. Weight loss, moisture content, and pH of egg yolk increased significantly (P < 0.05), whereas the yolk index decreased during storage. However, there was no significant difference in lipid profiles between 4 and 22°C storage temperature. The lipid composition analysis demonstrated that lipid hydrolysis took place during egg storage and resulted in a marked decrease of PL and increase of FFA. It was also found that the content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) decreased significantly during storage. The correlation analysis showed that the lipid degradation is significantly positively related to lipase activity (P < 0.05), and the marked changes of lipid fractions are results of both hydrolysis and oxidation. It can be concluded that the egg physicochemical index and lipase activity were greatly influenced by temperature during storage, but the yolk lipid stability was not significantly influenced by storage temperature.