Targeted inhibition of ß-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-ß1.

BACKGROUND: TGF-ß1 is a key cytokine involved in both airway inflammation and airway remodeling in asthma because of its anti-inflammatory and profibrotic effect. In our previous study, we found that knockdown of cytosolic ß-catenin alleviated the profibrogenic effect of TGF-ß1 without influencing its anti-inflammatory effect. However, the exact role of targeting ß-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting ß-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. METHODS: We integrated experimental asthma model and asthma related cell model to explore the effect of targeting ß-catenin on airway inflammation and remodeling of asthma. RESULTS: Blocking ß-catenin with ICG001, a small molecule inhibitor of ß-catenin/TCF via binding to cAMP-response elementbinding protein, attenuated airway inflammation by increasing levels of anti-inflammation cytokines IL-10, IL-35 and decreasing levels of T helper (Th)2 cells and Th17 cytokine. Suppressing ß-catenin by ICG001 inhibited airway remodeling via reducing the level of TGF-ß1 and the expressions of Snail, MMP-7, MMP-9 and, up-regulating expression of E-cadherin, down-regulating expressions of α-SMA and Fn. Inhibition of ß-catenin with ICG001 suppressed TGF-ß1 induced proliferation and activation of CCC-REPF-1, blocked TGF-ß1 induced epithelial-mesenchymal transition (EMT) of RLE-6TN. CONCLUSION: Blockade of ß-catenin/TCF not only prevents TGF-ß1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing pro-inflammatory and anti-inflammatory cytokine. In conclusion, targeting ß-catenin specifically via inhibition of ß-catenin/TCF might be a new therapeutic strategy for asthma.The reviews of this paper are available via the supplemental material section.

Two-step pretreatment of corn stalk silage for increasing sugars production and decreasing the amount of catalyst.

The study investigated the effects of two-step pretreatment on fermentable sugar production from corn stalk silage. In the first step, the corn stalk silage was extracted by tepid water and then the solid was pretreated using Fe(NO(3))(3) as catalyst. The results showed that 45.8 g/100g DM total sugars was obtained and the surface of remaining solid was seriously damaged after two-step pretreatment. Compared with one-step pretreatment, the production of total sugars increased by 23.8% and the amount of the catalyst of Fe(NO(3))(3) decreased by 28.8%. This research provides a new effective, suitable and economical pretreatment method for biogas production from corn stalk.