Oxidative stress disturbs energy metabolism of mitochondria in ethanol-induced gastric mucosa injury

AIM: To study the role of mitochondrial energy disorder in the pathogenesis of ethanol-induced gastric mucosa injury. METHODS: Wistar rats were used in this study. A gastric mucosal injury model was established by giving the rats alcohol. Gross and microscopic appearance of gastric mucosa and ultrastructure of mitochondria were evaluated. Malondiadehyde (MDA) in gastric mucosa was measured with thiobarbituric acid. Expression of ATP synthase (ATPase) subunits 6 and 8 in mitochondrial DNA (mtDNA) was determined by reverse transcription polymerase chain reaction (RT- PCR). RESULTS:The gastric mucosal lesion index was correlated with the MDA content in gastric mucosa. As the concentration of ethanol was elevated and theexposure time to ethanol was extended, the content of MDA in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of mitochondria was positively related to the ethanol concentration and exposure time. The expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content in gastric mucosa after gavage with ethanol. CONCLUSION: Ethanol-induced gastric mucosa injury is related to oxidative stress, which disturbs energy metabolism of mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric mucosa injury.

Reactive oxygen species: A double-edged sword in oncogenesis

Reactive oxygen species (ROS) are molecules or ions formed by the incomplete one-electron reduction of oxygen. Ofinterest, it seems that ROS manifest dual roles, cancer promoting or cancer suppressing, in tumorigenesis. ROS participate simultaneously in two signaling pathways that have inverse functions in tumorigenesis, Ras-Raf-MEK1/2-ERK1/2 signaling and the p38 mitogen-activated protein kinases (MAPK) pathway. It is well known that Ras-Raf-MEK1/2-ERK1/2 signaling is related to oncogenesis, while the p38 MAPK pathway contributes to cancer suppression, which involves oncogene-induced senescence, inflammationinduced cellular senescence, replicative senescence, contact inhibition and DNA-damage responses. Thus, ROS may not be an absolute carcinogenic factor or cancer suppressor. The purpose of the present review is to discuss the dual roles of ROS in the pathogenesis of cancer, and the signaling pathway mediating their role in tumorigenesis.

Precise prediction model and simplified scoring system for sustained combined response to interferon-α

AIM:To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-α(IFN-α) treatment.METHODS:A total of 474 IFN-α treated hepatitis B virus e antigen(HBeAg)-positive patients were enrolled in the present study.The patients' baseline characteristics,such as age,gender,blood tests,activity grading(G) of intrahepatic inflammation,score(S) of liver fibrosis,hepatitis B virus(HBV) DNA and genotype were evaluated;therapy duration and response of each patient at the 24th wk after cessation of IFN-α treatment were also recorded.A predictive algorithm and scoring system for a sustained combined response(CR) to IFN-α therapy were established.About 10% of the patients were randomly drawn as the test set.Responses to IFN-α therapy were divided into CR,partial response(PR) and non-response(NR).The mixed set of PR and NR was recorded as PR+NR.RESULTS:Stratified by therapy duration,the most significant baseline predictive factors were alanine aminotransferase(ALT),HBV DNA level,aspartate aminotransferase(AST),HBV genotype,S,G,age and gender.According to the established model,the accuracies for sustained CR and PR+NR,respectively,were 86.4% and 93.0% for the training set,81.5% and 91.0% for the test set.For the scoring system,the sensitivity and specificity were 78.8% and 80.6%,respectively.There were positive correlations between ALT and AST,and G and S,respectively.CONCLUSION:With these models,practitioners may be able to propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.