Proteomic and microbial assessments on the effect of Antrodia cinnamomea in C57BL/6 mice.

Antrodia cinnamomea (AC) is a nutraceutical fungus and studies have suggested that AC has the potential to prevent or alleviate diseases. However, little is known about the AC-induced phenotypes on the intestine-liver axis and gut microbial alterations. Here, we performed two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-Biotyper to elaborate the AC-induced phenotypes on the intestine-liver axis and gut microbial distribution of C57BL/6 mice. The experimental outcomes showed that the hepatic density may increase by elevating hepatic redox regulation, lipid degradation and glycolysis-related proteins and alleviating cholesterol biosynthesis and transport-related proteins in C57BL/6 mice with AC treatment. Moreover, AC facilitates intestinal glycolysis, TCA cycle, redox and cytoskeleton regulation-related proteins, but also reduces intestinal vesicle transport-related proteins in C57BL/6 mice. However, the body weight, GTT, daily food/water intake, and fecal/urine weight were unaffected by AC supplementation in C57BL/6 mice. Notably, the C57BL/6-AC mice had a higher gut microbial abundance of Alistipes shahii (AS) than C57BL/6-Ctrl mice. In summary, the AC treatment affects intestinal permeability by regulating redox and cytoskeleton-related proteins and elevates the gut microbial abundance of AS in C57BL/6 mice that might be associated with increasing hepatic density and metabolism-related proteins of the liver in C57BL/6 mice. Our study provides an insight into the mechanisms of AC-induced phenotypes and a comprehensive assessment of AC's nutraceutical effect in C57BL/6 mice.

Statin-conferred enhanced cellular resistance against bacterial pore-forming toxins in airway epithelial cells.

Statins are widely used to prevent cardiovascular disease. In addition to their inhibitory effects on cholesterol synthesis, statins have beneficial effects in patients with sepsis and pneumonia, although molecular mechanisms have mostly remained unclear. Using human airway epithelial cells as a proper in vitro model, we show that prior exposure to physiological nanomolar serum concentrations of simvastatin (ranging from 10-1,000 nM) confers significant cellular resistance to the cytotoxicity of pneumolysin, a pore-forming toxin and the main virulence factor of Streptococcus pneumoniae. This protection could be demonstrated with a different statin, pravastatin, or on a different toxin, α-hemolysin. Furthermore, through the use of gene silencing, pharmacological inhibitors, immunofluorescence microscopy, and biochemical and metabolic rescue approaches, we demonstrate that the mechanism of protection conferred by simvastatin at physiological nanomolar concentrations could be different from the canonical mevalonate pathways seen in most other mechanistic studies conducted with statins at micromolar levels. All of these data are integrated into a protein synthesis-dependent, calcium-dependent model showing the interconnected pathways used by statins in airway epithelial cells to elicit an increased resistance to pore-forming toxins. This research fills large gaps in our understanding of how statins may confer host cellular protection against bacterial infections in the context of airway epithelial cells without the confounding effect from the presence of immune cells. In addition, our discovery could be potentially developed into a host-centric strategy for the adjuvant treatment of pore-forming toxin associated bacterial infections.

Identification of gene transcripts in rat frontal cortex that are regulated by repeated electroconvulsive seizure treatment.

BACKGROUND/AIMS: Electroconvulsive therapy (ECT) is an effective treatment modality for severe psychiatric disorders. Many studies have suggested that the therapeutic efficacy of ECT can be attributed to the structural and functional readjustment of the brain cells, which is mediated by differential gene expression in the brain. The aim of this study is to understand the molecular mechanism of ECT. METHODS: We used microarray-based gene expression profiling technology and real-time quantitative PCR (RT-qPCR) to screen differentially expressed genes in the brain in a rat model of ECT. RESULTS: Four upregulated and three downregulated genes were identified in this study. The 4 upregulated genes are S100 protein, beta polypeptide (S100b), S100 calcium binding protein A13_predicted (S100a13_predicted), diazepam-binding inhibitor (Dbi), and YKT6 homolog (S. Cerevisiae) (Ykt6), respectively; while the 3 downregulated genes are basigin (Bsg), histidine triad nucleotide binding protein 1(Hint 1), and neural precursor cell expressed, developmentally downregulated gene 8 (Nedd8), respectively. CONCLUSION: In view of the neurobiological function of these genes and their relevance to mental disorders, repeated ECS can affect gene expression involved in the neurotransmission and synaptic plasticity, which may account for the clinical effects of ECT.