Synergistic Interaction of Light Alcohol Administration in the Presence of Mild Iron Overload in a Mouse Model of Liver Injury: Involvement of Triosephosphate Isomerase Nitration and Inactivation.

It is well known that iron overload promotes alcoholic liver injury, but the doses of iron or alcohol used in studies are usually able to induce liver injury independently. Little attention has been paid to the coexistence of low alcohol consumption and mild iron overload when either of them is insufficient to cause obvious liver damage, although this situation is very common among some people. We studied the interactive effects and the underlining mechanism of mild doses of iron and alcohol on liver injury in a mouse model. Forty eight male Kunming mice were randomly divided into four groups: control, iron (300 mg/kg iron dextran, i.p.), alcohol (2 g/kg/day ethanol for four weeks i.g.), and iron plus alcohol group. After 4 weeks of treatment, mice were sacrificed and blood and livers were collected for biochemical analysis. Protein nitration level in liver tissue was determined by immunoprecipitation and Western blot analysis. Although neither iron overload nor alcohol consumption at our tested doses can cause severe liver injury, it was found that co-administration of the same doses of alcohol and iron resulted in liver injury and hepatic dysfunction, accompanied with elevated ratio of NADH/NAD+, reduced antioxidant ability, increased oxidative stress, and subsequent elevated protein nitration level. Further study revealed that triosephosphate isomerase, an important glycolytic enzyme, was one of the targets to be oxidized and nitrated, which was responsible for its inactivation. These data indicate that even under low alcohol intake, a certain amount of iron overload can cause significant liver oxidative damage, and the modification of triosephosphate isomerasemight be the important underlining mechanism of hepatic dysfunction

Research on feature extraction and classification of AE signals of fibers' tensile failure based on HHT and SVM

In order to study the feature extraction and recognition method of fibers' tensile failure, AE technology is used to collect AE signals of fiber bundle's tensile fracture of two kinds of fibers of Aramid 1313 and viscose. A transform called wavelet is used to deal with the signals to reduce noise. A method called Hilbert-Huang transform (HHT) is used to extract characteristic frequencies of the signals after the noise is reduced. And a classification method called Least Squares support vector machines (LSSVM) is used for the classification and recognition of characteristic frequencies of the two kinds of fibers. The results show that wavelet de-noise method can reduce some noise of the signals. Hilbert spectrum can reflect fracture circumstances of the two kinds of fibers in the time dimension to some extent. Characteristic frequencies' extraction can be done from marginal spectrum. The LSSVM can be used for the classification and recognition of characteristic frequencies. The recognition rates of Aramid 1313 and viscose reach 40%, 80% respectively, and the total recognition rate reaches 60%

Propagation law of impact elastic wave based on specific materials

In order to explore the propagation law of the impact elastic wave on the platform, the experimental platform is built by using the specific isotropic materials and anisotropic materials. The glass cloth epoxy laminated plate is used for anisotropic material, and an organic glass plate is used for isotropic material. The PVDF sensors adhered on the specific materials are utilized to collect data, and the elastic wave propagation law of different thick plates and laminated plates under impact conditions is analyzed. The Experimental results show that in anisotropic material, transverse wave propagation speed along the fiber arrangement direction is the fastest, while longitudinal wave propagation speed is the slowest. The longitudinal wave propagation speed in anisotropic laminates is much slower than that in the laminated thick plates. In the test channel arranged along a particular angle away from the central region of the material, transverse wave propagation speed is larger. Based on the experimental results, this paper proposes a material combination mode which is advantageous to elastic wave propagation and diffusion in shock-isolating materials. It is proposed to design a composite material with high acoustic velocity by adding regularly arranged fibrous materials. The overall design of the barrier material is a layered structure and a certain number of 90°zigzag structure

Lipid peroxidation, total GSH content and antioxidant enzymes activities in the liver of different groups.

<p>Lipid peroxidation, total GSH content and antioxidant enzymes activities in the liver of different groups.</p

Biochemical indicators of liver function in serum and histological changes in the liver.

<p>(a) Serum aspartate aminotransferase (AST) activity, (b) alanine aminotransferase (ALT) activity, and (c) the <i>arrows</i> showed karyorrhexis and cytolysis necrosis in fixed liver tissue sections stained with H&E (magnification 400×). Group C, control; group I, iron 300 mg/kg; group A, ethanol 2 g/kg/day; group IA, iron 300 mg/kg + ethanol 2 g/kg/day. Values are expressed as means±SEM, ^##p<0.01, ^###p<0.001 vs. groupC; ^*p<0.05, ^***p<0.001 vs. groupIA.</p

The plausible mechanism of liver injury induced by low doses of alcohol and iron overload.

<p>Co-exposure to alcohol and iron led to elevated NADH/NAD⁺ ratio and ROS/RNS, as well as low expression and activity of TIM. Oxidative/nitrative modifications of TIM caused the enzyme inactivity. The disturbed balance of NADH/NAD⁺ ratio and decreased expression and activity of TIM caused by a combination use of iron and ethanol, was hypothesized to favor the abnormalities in energy metabolism and hepatic lipid accumulation associated with liver disease.</p

Nitrative stress in the liver of different treated groups.

<p>(a) Hepatic iNOS expression, (b) serum NO content, and (c) hepatic protein nitration level. (d) and (e) the corresponding densitometric analysis of iNOS expression and total nitration status of liver protein. The respective control values were set to 100%, to which the other groups’ values were compared. Group C, control; group I, iron 300 mg/kg; group A, ethanol 2 g/kg/day; group IA, iron 300 mg/kg + ethanol 2 g/kg/day. Values are expressed as means±SEM, ^#p<0.05, ^##p<0.01, ^###p<0.001 vs.groupC; ^*p<0.05, ^**p<0.01, ^***p<0.001 vs. groupIA.</p

Effects of chemical regents on TIM activity.

<p>(a) Effects of N-ethyl-maleimide on TIM activity. (b) Effects of 1-acetyl-imidazole on TIM activity. ^#P< 0.05, ^##P< 0.01, ^###p < 0.001.</p

TIM expression, oxidation, nitration and catalytic activity in livers of different treated groups.

<p>(a) Hepatic TIM expression and (b) the corresponding densitometric analysis. (c) Oxidation and nitration status of hepatic TIM. (d) The corresponding densitometric analysis of TIM oxidation. (e) The corresponding densitometric analysis of nitration. (f) The ratio of TIM oxidation to total TIM expression. (g) The ratio of TIM nitration to total TIM expression. (h) TIM activity. Equal amounts of protein were immunoprecipitated by anti-TIM antibody, and immunoprecipitates were analyzed for oxidation and nitration status of TIM by Western blot. The respective control values were set to 100%, to which the other groups’ values were compared. Group C, control; group I, iron 300 mg/kg; group A, ethanol 2 g/kg/day; group IA, iron 300 mg/kg + ethanol 2 g/kg/day. Values are expressed as means±SEM, ^#p<0.05, ^##p<0.01, ^###p<0.001 vs. group C; ^**p<0.01, ^***p<0.001 vs. group IA.</p

Total oxidative status of hepatic protein in different treated groups.

<p>(a) Protein carbonylation of liver, and (b) the corresponding densitometric analysis. Normal values were set to 100%, with which other values were compared. Group C, control; group I, iron 300 mg/kg; group A, ethanol 2 g/kg/day; group IA, iron 300 mg/kg + ethanol 2 g/kg/day. Values are expressed as means±SEM, obtained from nine mice of each group. All visible bands were quantified. ^##p<0.01, ^###p<0.001 vs. groupC; ^**p<0.01 vs. groupIA.</p