BackgroundTransforming growth factor-β (TGF-β) plays a paradoxical role in cancer: it suppresses proliferation at early stages but promotes metastasis at late stages. This cytokine is upregulated in cholangiocarcinoma and is implicated in cholangiocarcinoma invasion and metastasis. Here we investigated the roles of non-Smad pathway (ERK1/2) and Smad in TGF-β tumor promoting and suppressing activities in intrahepatic cholangiocarcinoma (ICC) cells.MethodsTGF-β1 effects on proliferation, invasion and migration of ICC cells, KKU-M213 and/or HuCCA-1, were investigated using MTT, colony formation, in vitro Transwell and wound healing assays. Levels of mRNAs and proteins/phospho-proteins were measured by quantitative (q)RT-PCR and Western blotting respectively. E-cadherin localization was examined by immunofluorescence and secreted MMP-9 activity was assayed by gelatin zymography. The role of ERK1/2 signaling was evaluated by treating cells with TGF-β1 in combination with MEK1/2 inhibitor U0126, and that of Smad2/3 and Slug using siSmad2/3- and siSlug-transfected cells.Resultsh-TGF-β1 enhanced KKU-M213 cell invasion and migration and induced epithelial-mesenchymal transition as shown by an increase in vimentin, Slug and secreted MMP-9 levels and by a change in E-cadherin localization from membrane to cytosol, while retaining the cytokine’s ability to attenuate cell proliferation. h-TGF-β1 stimulated Smad2/3 and ERK1/2 phosphorylation, and the MEK1/2 inhibitor U0126 attenuated TGF-β1-induced KKU-M213 cell invasion and MMP-9 production but moderately enhanced the cytokine growth inhibitory activity. The latter effect was more noticeable in HuCCA-1 cells, which resisted TGF-β-anti-proliferative activity. Smad2/3 knock-down suppressed TGF-β1 ability to induce ERK1/2 phosphorylation, Slug expression and cell invasion, whereas Slug knock-down suppressed cell invasion and vimentin expression but marginally affected ERK1/2 activation and MMP-9 secretion. These results indicate that TGF-β1 activated ERK1/2 through Smad2/3 but not Slug pathway, and that ERK1/2 enhanced TGF-β1 tumor promoting but repressed its tumor suppressing functions.ConclusionsInhibiting ERK1/2 activation attenuates TGF-β1 tumor promoting effect (invasion) but retains its tumor suppressing role, thereby highlighting the importance of ERK1/2 in resolving the TGF-β paradox switch.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-017-0454-2) contains supplementary material, which is available to authorized users.
Coronavirus disease (COVID-19) cases are continuing to rise around the world, with more than 607 million confirmed cases and more than 6.51 million deaths as of September 2022. The World Health Organization (WHO) has emphasized the importance of hygiene in the ongoing COVID-19 pandemic, especially in elderly and bedridden patients. The use of no-rinse shampoo represents a simple change in hair-cleansing products. Daily hospital hair washing for the elderly, bedridden, and ICU patients would be more readily adopted. The objective of this study was to design and optimize a new no-rinse shampoo based on electrochemically reduced water (ERW) using response surface methodology. The relationship between coconut-based surfactant mixtures in a no-rinse shampoo and the resulting physicochemical properties, effectiveness (antibacterial and antifungal activity), and stability of the shampoo was investigated. The vesicle size, size distribution, zeta potential, conductivity, pH, foamability, wetting time, turbidity, and stability of the model formulation were optimized. The optimal formulation with the appropriate physicochemical properties and stability was selected. The effectiveness of the optimal formulation was compared to that of commercially available products. The dry shampoo (DS4) containing 3.5% of the mixed detergent with ERW may prevent infection by Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans. The no-rinse shampoo based on ERW successfully demonstrated good stability in addition to efficacy in terms of antibacterial and antifungal activity. The treated hair fiber was not significantly different from that of the intact hair fiber. Under the scanning electron microscopy (SEM) and the atomic force microscopy (AFM), the cuticle layer of the treated hair fiber was not damaged. Thus, no-rinse shampoos may reduce the time of hair rinsing and improve the quality of life of caregivers.
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