Chitosan oligosaccharide ameliorates acute lung injury induced by blast injury through the DDAH1/ADMA pathway.

OBJECTIVE: To investigate the protective effect of chitosan oligosaccharide (COS) on acute lung injury (ALI) caused by blast injury, and explore possible molecular mechanisms. METHODS: A mouse model of blast injury-induced ALI was established using a self-made explosive device. Thirty mice were randomly assigned to control, ALI and ALI + COS groups. An eight-channel physiological monitor was used to determine the mouse physiological index. Enzyme linked immunosorbent assay was used to measure serum inflammatory factors. Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, immunofluorescence staining, real time-polymerase chain reaction and western blot assay were used to detect inflammatory reactions, oxidative stress and apoptosis. RESULTS: Mice were sacrificed 24 hours after successful model induction. Compared with the ALI group, the heart rate, respiration and PCO2 were significantly lower, but the PO2, TCO2 and HCO3- were significantly higher in the ALI + COS group. Compared to ALI alone, COS treatment of ALI caused a significant decrease in the wet/dry lung weight ratio, indicating a reduction in lung edema, inflammatory cell infiltration, levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-4, IL-6 and nuclear factor kappa B mRNA and protein expression were reduced and IL-10 mRNA and protein expression was increased (P < 0.05). COS significantly inhibited reactive oxygen species, MDA5 and IREα mRNA and protein expressions, cell apoptosis and Bax and Caspase-3 mRNA and protein expressions, and significantly increased superoxide dismutase-1 mRNA expression, and Bcl-2 and Caspase-8 mRNA and protein expression (all P<0.05). COS significantly increased dimethylarginine dimethylaminohydrolase 1 (DDAH1) protein expression, and reduced ADMA and p38 protein expression (P< 0.05). CONCLUSION: Blast injury causes inflammation, oxidative stress and apoptosis in the lung tissues of mice. COS has protective effects on blast injury-induced ALI, possibly by promoting DDAH1 expression and inhibiting ADMA and mitogen-activated protein kinase pathways.

Growth inhibition and apoptosis induction by alternol in pancreatic carcinoma cells.

AIM: To investigate the effect of alternol on pancreatic cancer cells. METHODS: Pancreatic cancer cells PANC-1 and BxPC3 were treated with various concentrations of alternol for 24, 48 and 72 h. Cell proliferation was measured by cell counting. Cell cycle distribution and mitochondrial membrane potential were determined by flow cytometry. Apoptosis was determined by a TdT-mediated dUTP nick end labeling assay and Hoechst staining. Expression of caspase 3, Bcl-2, p53 and p21 was measured by western blotting. RESULTS: Alternol showed dose- and time-dependent inhibition of the proliferation of PANC-1 and BxPC3 cells in vitro. Alternol induced apoptosis and cell cycle arrest at S phase and decreased mitochondrial membrane potential. Alternol activated caspase 3, upregulated p53 and p21 expression, and downregulated Bcl-2 expression in a dose-dependent manner. CONCLUSION: Our results suggested that alternol is a candidate for treatment of pancreatic cancer.

Alternol inhibits migration and invasion of human hepatocellular carcinoma cells by targeting epithelial-to-mesenchymal transition.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Such deaths are due, in large part, to its propensity to metastasize. We have examined the effect of alternol on human HCC cells and the underlying molecular mechanism. Therapeutic effects of alternol on cancer cell migration and invasion were analyzed with Boyden chamber and wound healing assays. Effects of alternol on the levels of various proteins involved in cancer cell migration and invasion were determined with gelatin zymography, immunofluorescence, and Western blotting. As shown, treatment with alternol has resulted in a concentration-dependent inhibition of cell migration and invasion of HepG2 cells. The inhibition of HCC invasion by alternol was associated with the suppression of MMP-9 expression and reversal of epithelial-to-mesenchymal transition (EMT). The above results indicated that alternol has the ability to inhibit the migration and invasion of human HCC cells by reversing the process of EMT, suggesting that alternol may be developed as an alternative drug for the treatment of HCC.