Notch1 is an evolutionarily conserved receptor that regulates cell fate, including such events as differentiation, proliferation, and apoptosis. Myofibroblast differentiation is a key feature of lung fibrosis. Found in inflammatory zone 1 (FIZZ1) has direct fibrogenic properties because of its ability to induce myofibroblast differentiation. However, the downstream signaling pathway that mediates FIZZ1 induction of myofibroblast differentiation remains unknown. The objective of this study was to investigate the involvement of Notch signaling in FIZZ1 induction of lung myofibroblast differentiation and thus explore the potential role of Notch1 in pulmonary fibrosis. The results showed that FIZZ1 increased the expression levels of activated intracellular domain of Notch1 (NIC), its ligand Jagged1, and its target gene Hes1, which were associated with elevated ␣-smooth muscle actin expression levels. Fibroblast ␣-smooth muscle actin expression is induced by the overexpression of NIC but is suppressed by the inhibition of NIC. Moreover, lung fibroblasts that were isolated from mice lacking the GDP-4-keto-6-deoxymannose3,5-epimerase-4-reductase enzyme (FX knockout) exhibited significantly reduced responsiveness to FIZZ1, which was reversed by fucose supplementation. In the absence of exogenous fucose, these FX-deficient cells exhibited defective fucosylation, which is required for Notch signaling. These knockout mice also showed impaired lung fibrosis. These findings suggest that Notch1 signaling in response to FIZZ1 may play a significant role in myofibroblast differentiation during lung fibrosis.

An acidic polysaccharide CS-F2 from Camellia sinensis was examined to characterize its anti-adhesive effects against pathogenic bacteria, most notably Helicobacter pylori, Propionibacterium acnes, and Staphylococcus aureus. CS-F2 showed marked inhibitory activity against the pathogen-mediated hemagglutination with a minimum inhibitory concentration (MIC) between 0.01 and 0.1 mg/mL, which is lower than the previously reported MIC values for Panax ginseng and Artemisia capillaris. The inhibitory effects of CS-F2 on the adhesion of H. pylori to AGS adenocarcinoma gastric epithelial cells, or P. acnes and S. aureus to NIH 3T3 fibroblast cells, were further assessed resulting in MIC values between 0.063 and 0.13 mg/mL. Importantly, CS-F2 showed no inhibitory effects against Lactobacillus acidophilus, Escherichia coli, or Staphylococcus epidermidis. Our results suggest that CS-F2, which is a pectin-type polysaccharide with a molecular weight of approximately 8.0 x 10(4) Da, may exert a selective anti-adhesive effect against certain pathogenic bacteria, while exerting no effects against beneficial and commensal bacteria.

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Influenza is a serious public health concern worldwide, as it causes significant morbidity and mortality. The emergence of drug-resistant viral strains requires new approaches for the treatment of influenza. In this study, Rubus coreanus seed (RCS) that is left over from the production of wine or juice was found to show antiviral activities against influenza type A and B viruses. Using the time-of-addition plaque assay, viral replication was almost completely abolished by simultaneous treatment with the RCS fraction of less than a 1-kDa molecular weight (RCSF1). One of the polyphenols derived from RCSF1, gallic acid (GA), identified by liquid chromatography-tandem mass spectrometry, showed inhibitory effects against both influenza type A and B viruses, albeit at relatively high concentrations. RCSF1 was bound to hemagglutinin protein, inhibited hemagglutination significantly and disrupted viral particles, whereas GA was found to only disrupt the viral particles by using transmission electron microscopy. In BALB/c mice infected with influenza virus, oral administration of RCSF1 significantly improved the survival rate and reduced the viral titers in the lungs. Our results demonstrate that RCSF1 and GA show potent and broad antiviral activity against influenza A and B type viruses and are promising sources of agents that target virus particles.