Septin 9 hypermethylation contributes to migration and resistance to drug treatments in colon cancer

Purpose: To examine septin 9 gene-promoter methylation content in colorectal cancer and establish its significance in cancer progression and chemoresistance.Methods: Patient samples and colorectal cancer cell lines (CRC) were evaluated for septin 9 expression and promoter hypermethylation content. Septin 9 promoter methylation and expression in cells were perturbed by 5-AZA (5-aza-2'-deoxycytidine) treatments or overexpression and probed for changes in Rho A signaling, cell proliferation, and migration. Finally, the significance of septin 9 methylation in chemoresistance was probed using apoptotic assays in CRC cells and in a xenograft tumor model.Results: Expression analysis showed a reduction in septin 9 levels in tumor tissues (p < 0.001) and cell lines (p < 0.01), while an increase in septin 9 promoter methylation was seen, respectively ( > 2-fold; p < 0.01). Increasing septin 9 levels in CRC cells by 5-AZA treatments or overexpression showed decreased Rho A signaling and cell migration (p < 0.01), whereas cell proliferation remained unaffected. Furthermore, increasing septin 9 levels also exhibited increased cisplatin-induced apoptosis in CRC cells and reduced chemoresistance in the mouse (~2-fold; p < 0. 01).Conclusion: Septin 9 promoter hypermethylation reduces septin 9 expression and promotes migration and chemoresistance.Keywords: Septin 9, Hypermethylation, Colorectal cancer, Drug resistance, Rho A signalin

Raw rehmannia radix polysaccharide can effectively release peroxidative injury induced by duck hepatitis A virus

Background: Duck viral hepatitis (DVH), caused by duck hepatitis A virus (DHAV), is a fatal contagious infectious disease which spreads rapidly with high morbidity and high mortality, and there is no effective clinical drug against DVH.Materials and Methods: Raw Rehmannia Radix Polysaccharide (RRRP), Lycii Fructus polysaccharides and Astragalus Radix polysaccharides were experimented in vitro and in vivo. Mortality rate, livers change, liver lesion scoring, peroxidative injury evaluation indexes in vitro and in vivo, and hepatic injury evaluation indexes of optimal one were detected and observed in this experiment.Results: RRRP could reduce mortality with the protection rate about 20.0% compared with that of the viral control (VC) group, finding that RRRP was the most effective against DHAV. The average liver scoring of the VC, blank control (BC), RRRP groups were 3.5, 0, 2.1. Significant difference (P<0.05) appeared between any two groups, demonstrating that it can alleviate liver pathological change. RRRP could make the hepatic injury evaluation indexes similar to BC group while the levels of the VC group were higher than other two groups in general. The levels of SOD, GSH-Px, CAT of RRRP group showed significant higher than that of VC group while the levels of NOS and MDA showed the opposite tendency, thus, RRRP could release peroxidative injury.Conclusion: RRRP was the most effective against duck hepatitis A virus (DHAV). RRRP could reduce mortality, alleviate liver pathological change, down-regulate liver lesion score, release peroxidative injury and hepatic injury. The antiviral and peroxidative injury releasing activity of RRRP for DHAV provided a platform to test novel drug strategies for hepatitis A virus in human beings.Keywords: Raw Rehmannia Radix Polysaccharide; duck hepatitis A virus; peroxidative injury; hepatic injur

RAW REHMANNIA RADIX POLYSACCHARIDE CAN EFFECTIVELY RELEASE PEROXIDATIVE INJURY INDUCED BY DUCK HEPATITIS A VIRUS

Background: Duck viral hepatitis (DVH), caused by duck hepatitis A virus (DHAV), is a fatal contagious infectious disease which spreads rapidly with high morbidity and high mortality, and there is no effective clinical drug against DVH. Materials and Methods: Raw Rehmannia Radix Polysaccharide (RRRP), Lycii Fructus polysaccharides and Astragalus Radix polysaccharides were experimented in vitro and in vivo. Mortality rate, livers change, liver lesion scoring, peroxidative injury evaluation indexes in vitro and in vivo, and hepatic injury evaluation indexes of optimal one were detected and observed in this experiment. Results: RRRP could reduce mortality with the protection rate about 20.0% compared with that of the viral control (VC) group, finding that RRRP was the most effective against DHAV. The average liver scoring of the VC, blank control (BC), RRRP groups were 3.5, 0, 2.1. Significant difference (

Phosphorylation of Icariin Can Alleviate the Oxidative Stress Caused by the Duck Hepatitis Virus A through Mitogen-Activated Protein Kinases Signaling Pathways

The duck virus hepatitis (DVH) caused by the duck hepatitis virus A (DHAV) has produced extensive economic losses to the duck industry. The currently licensed commercial vaccine has shown some defects and does not completely prevent the DVH. Accordingly, a new alternative treatment for this disease is urgently needed. Previous studies have shown that icariin (ICA) and its phosphorylated derivative (pICA) possessed good anti-DHAV effects through direct and indirect antiviral pathways, such as antioxidative stress. But the antioxidant activity showed some differences between ICA and pICA. The aim of this study is to prove that ICA and pICA attenuate oxidative stress caused by DHAV in vitro and in vivo, and to investigate their mechanism of action to explain their differences in antioxidant activities. In vivo, the dynamic deaths, oxidative evaluation indexes and hepatic pathological change scores were detected. When was added the hinokitiol which showed the pro-oxidative effect as an intervention method, pICA still possessed more treatment effect than ICA. The strong correlation between mortality and oxidative stress proves that ICA and pICA alleviate oxidative stress caused by DHAV. This was also demonstrated by the addition of hydrogen peroxide (H2O2) as an intervention method in vitro. pICA can be more effective than ICA to improve duck embryonic hepatocytes (DEHs) viability and reduce the virulence of DHAV. The strong correlation between TCID50 and oxidative stress demonstrates that ICA and pICA can achieve anti-DHAV effects by inhibiting oxidative stress. In addition, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of ICA and pICA showed significant difference. pICA could significantly inhibit the phosphorylation of p38, extra cellular signal regulated Kinase (ERK 1/2) and c-Jun N-terminal kinase (JNK), which were related to mitogen-activated protein kinases (MAPKs) signaling pathways. Ultimately, compared to ICA, pICA exhibited more antioxidant activity that could regulate oxidative stress-related indicators, and inhibited the phosphorylation of MAPKs signaling pathway

Solvothermal synthesis and photocatalytic performance of Mg2+-doped anatase nanocrystals with exposed {0 0 1} facets

The photocatalytic activity of TiO2 and magnesium doped TiO 2 nanocrystals in dopant range of 2-6.2 at%, was studied. The doped and undoped nanocrystals with exposed {0 0 1} crystal facets were synthesized by a solvothermal method. Several studies have shown that the (0 0 1) surface of the TiO2 anatase crystal is more reactive than the thermodynamically stable (1 0 1) surface. The crystal structure as well as the shape of the TiO2 and Mg2+/TiO2 anatase nanoparticles were determined using two different techniques, such as X-ray powder diffraction (XRD) and transmission electron microscopy (TEM), which both lead to the agreeable conclusion that the nanocrystals are in the form of plates. Chemical analysis of the photocatalyst was carried out with X-ray photoelectron spectroscopy (XPS) and showed the presence of magnesium ions in the TiO 2 nanoplates. UV-vis diffuse reflectance spectroscopy (DRS) showed that there is an adsorption shift for doped TiO2 to visible light region. The photocalaytic efficiency of the synthesized catalysts was investigated by the photocatalytic oxidation of the gaseous nitric oxide (NO) and decomposition of the gaseous acetaldehyde (CH3CHO) under UV irradiation. It was demonstrated that the low Mg2+ doped catalysts exhibited higher photocatalytic activity than the pure TiO2. The optimal concentration of dopant that is beneficial for the photocatalytic activity was studied. © 2013 Elsevier B.V

An Integrated Method of Supply Chains Vulnerability Assessment

Supply chain vulnerability identification and evaluation are extremely important to mitigate the supply chain risk. We present an integrated method to assess the supply chain vulnerability. The potential failure mode of the supply chain vulnerability is analyzed through the SCOR model. Combining the fuzzy theory and the gray theory, the correlation degree of each vulnerability indicator can be calculated and the target improvements can be carried out. In order to verify the effectiveness of the proposed method, we use Kendall’s tau coefficient to measure the effect of different methods. The result shows that the presented method has the highest consistency in the assessment compared with the other two methods