Episomal Lentiviral Vector-Mediated miR-145 Overexpression Inhibits Proliferation and Induces Apoptosis of Human Esophageal Carcinomas Cells.

BACKGROUND: Gene therapy is a promising approach for the treatment of various cancers. However, most viral vectors used for this purpose carry risks, including potential integration into the host genome. OBJECTIVE: We addressed this issue in the present study by constructing an episomal lentiviral vector using the .-interferon matrix attachment region to express the microRNA -145(miR-145), and examining the effect of miR-145 overexpression on human esophageal carcinomas (EC) cells. Some recent relevant patents are also discussed. METHOD: Expression levels of miR-145 and the marker protein enhanced green fluorescent protein (EGFP) in infected ECA109 and EC9706 human esophageal carcinoma cells were detected by quantitative PCR and flow cytometry, respectively. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 and flow cytometry, respectively. Plasmid rescue experiments and fluorescence in situ hybridization were used to determine the episomal status of the transfected vector. RESULTS: We found that EGFP and miR-145 were highly expressed in EC cells, and miR-145 overexpression inhibited cell proliferation and induced apoptosis. Moreover, the lentiviral vector did not integrate into the host genome, but was maintained episomally at lower copy numbers. CONCLUSION: Taken together, our results demonstrate that miR-145-expressing episomal lentiviral vectors are a promising tool for gene therapy in the treatment of EC.

Cardioprotective effect of resveratrol on atherogenic diet-fed rats.

Atherogenic or high fat diets were known to induce cardiovascular diseases, and several active compounds were tested to protect/prevent the risk of cardiovascular diseases. We aimed to investigate the cardio protective effect of resveratrol against atherogenic diet fed rats. Male Wistar rats were administered atherogenic diet for 30 days and further continued for 15 days with or with resveratrol in the diet. The serum lipid profile, antioxidant enzyme activity, lipid peroxidation, lipid metabolic proteins and cardiac tissue markers were examined. The histopathology of myocardium and aorta were also examined. The abnormal serum lipid profile found in atherogenic rats was reversed by the administration of resveratrol. Similarly, the enzymatic (catalase, superoxide dismutase, glutathione-peroxidase), non-enzymatic (reduced-glutathione, Vitamin C, E) antioxidants were improved by the resveratrol fed against atherogenic diet. Interestingly, resveratrol activated the lipid metabolic proteins (SIRT1, eNOS and AMPKa), suggesting its protective effect on lipid metabolism. Further analysis on tissue damage revealed that resveratrol had significantly protected the tissue damage and maintains the morphology of cardiac tissue. Altogether, our results suggest that resveratrol played a significant role in the prevention of cardiovascular system against the high fat diet. Emphasising the anti-atherogenic property of resveratrol, we propose resveratrol as a potential compound to be consumed for the healthy life-style.

Neuroprotective effect of AG490 in experimental traumatic brain injury of rats.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide. Therefore, we investigated the role of AG490 in regulating brain oedema, expression of CD40 and neurological function after TBI. METHODS: Sprague Dawley rats (n = 240) were randomly divided into a sham operation group, TBI+saline group and TBI+AG490 (JAK/STAT inhibitor) group. Members of each group were euthanized at 6, 12, 24 or 72 hours after injury. Neurological severity score (NSS) was used to evaluate the severity of neurological damage. Brain water was quantitated by wet/dry weight method. The expression of CD40 was assessed by flow cytometry. RESULTS: In both the TBI+saline group and the TBI+AG490 group, the brain water content was elevated after TBI, reached a peak at 24-hour and remained high for the rest of the period investigated; the expression of CD40 reached a peak 24 hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours. Elevations in the level of CD40, degree of brain edema and NSS after TBI were significantly reduced in TBI+AG490 group. CONCLUSION: Inhibition of the JAK/STAT signalling pathway reduces brain oedema, decreases the expression of CD40 and exerts neuroprotective effects after TBI.