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Objective To investigate the role of p53 in the regulation of heat shock protein(Hsp)84 and 86,and the correlation of their functional imbalances with accelerated brain aging and with suppressed tumorigenesis in SAMP8 mice(senescence accelerated mouse prone 8).Methods The mRNA and protein expressions of Hsp84 and Hsp86,and protein expressions of p53 pathway-related proteins(p21 and MDM2)in hippocampus of SAMP8 mice and their control SAMR1(senescence accelerated mouse resistant 1)mice were determined.Murine Neuro-2a cells were treated with 20 μmol/L Aβ25-35,and then mRNA expressions of p53,Hsp84 and Hsp86 in these cells were detected.Neuro-2a cells were co-transfected with p53 siRNA and pHsp84-Luc or pHsp86-Luc plasmid and treated with 20 μmol/L Aβ25-35,then promoter activity of Hsp84 and Hsp86 were detected in these cells.After co-transfection with pcDNA3.1-p53 or pcDNA3.1-p53DD and pHsp84-Luc or pHsp86-Luc plasmids,the neuro-2a cells were treated with 20 μmol/L Aβ25-35.Then promoter activity of Hsp84 and Hsp86 were detected in these cells at different concentrations of p53.Results The mRNA levels of Hsp84 and Hsp86 in the hippocampus of SAMP8 mice were significantly declined,which were 13.51% and 16.13% of SAMR1 mice,respectively(all P<0.01).Compared with the SAMR1 mice,the protein expressions of Hsp84 and Hsp86 in the hippocampus of SAMP8 mice were obviously declined(all P<0.01).Whereas,p53 pathway-related protein p21 expression was increased and MDM2 expression was decreased(all P<0.01).The mRNA expression of p53 in AD cells was significantly increased by 58%(P<0.01),whereas Hsp84 and Hsp86 mRNA levels were significantly decreased by 32% and 41%,respectively as compared with the normal cells(all P<0.05).Inhibition of p53 in AD cells could increase promoter activity of Hsp84 and Hsp86 significantly in a concentration-dependent manner(both P<0.05),whereas overexpression of p53 in the cells could lead to decreased promoter activity of them in a concentration-dependent manner(both P<0.05).Conclusions The p53 can negatively regulate the expressions of Hsp84 and Hsp86.The activity of p53/p21 pathway is increased,while Hsp84 and Hsp86 are inhibited in the brain of SAMP8 mice.Functional imbalance between p53 and Hsp84/86 might be the part of reasons causing accelerated aging and suppressed tumorigenesis in SAMP8 mice.
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In order to carry out the training objectives ofexcellent doctor education training pro-gram implemented by the Ministry of Education and the Ministry of Health, an integrated organ-system oriented curriculum system of circulatory system was applied in five year clinical medicine education. The teaching contents of circulatory system from traditional Histology and Embryology, Physiology, Pathology, Pathophysiology, and Pharmacology were integrated and optimized to compile the integrated circulatory sys-tem textbook. problem-based learning (PBL) and comprehensive morphology experimental teaching were implemented into the integrated circulatory system curriculum. Diversified examination methods including continuous assessment of PBL were used to evaluate the learning effect of students. As a result, a new cur-riculum model of circulatory system teaching was constructed. And on the base of this curriculum model, an innovation course research experiment was performed, a digital network teaching platform with 4A (anybody, anything, anywhere, anytime) was set up, and diversified teaching methods were applied. This new developing curriculum system is helpful for students to relate what they have learned in the basic sci-ences to clinical medicine, gain clinical thinking competence, lifelong skills of self-directed learning, in-novative thinking, and ability of scientific research and practice.
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BACKGROUND:Liver fibrosis is a kind of chronic and active disease that is caused by various causes and characterized by the excessive accumulation of extracelular matrix. At present, use of Chinese herbs for the treatment of hepatic fibrosis has obvious advantages. Salvia miltiorrhiza has been shown to be highly effective in the treatment of hepatic fibrosis. However, the underlying mechanism needs further investigation. OBJECTIVE:To investigate the effects of TanshinoneⅡA on the expression levels of transforming growth factor-β/Smads signaling pathway related factors transforming growth factor-β, bone morphogenetic protein 7, Smad6 and Smad7 in the liver tissue of rats with hepatic fibrosis. METHODS:SD rats were randomly divided into three groups (n = 10): normal control, model and TanshinoneⅡA-treated groups. Rats in the model and TanshinoneⅡA-treated groups were subtaneously injected with olive oil-diluted 10% CCl4 ( 5 mL/kg) twice a week, 8 weeks in total, to build rat models of hepatic fibrosis. Four weeks after hepatic fibgrosis induction, rats in the TanshinoneⅡA-treated group received subtaneous injection of TanshinoneⅡA til eight weeks. Rats in the normal control group were subcutaneously injected with olive oil. RESULTS AND CONCLUSION: Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) detection showed that in the model group, the expression of transforming growth factor-β in the rat liver tissue was significantly increased (P < 0.01) and the expression of bone morphogenetic protein-7, Smad6 and Smad7 was significantly decreased (P < 0.01) compared with the normal control group. TanshinoneⅡA could obviously reverse the expression of those factors above-mentioned (P < 0.01). The results suggest that TanshinoneⅡA can be used for treatment of hepatic fibrosis by decreasing the expression of transforming growth factor-β and increasing the expression of bone morphogenetic protein-7, Smad6 and Smad7.
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Objective To verify the validity of the sucrose density gradient ultracentrifugation method for lipid rafts from cerebral cortex. Methods Extract lipid rafts from cerebral cortex in mouse were extracted by the sucrose density gradi-ent ultracentrifugation method. The properties of lipid rafts were detected by Western blotting method, double enzyme and light scattering methods. HPLC MS/MS proteomics and bioinformatics were used to locate proteins of lipid rafts in cells. Re-sults Lipid rafts from cerebral cortex were provided with the model properties of lipid rafts such as high light scattering and cholesterol and high expression of Flotillin-1. HPLC MS/MS proteomics identified total 647 proteins. Most of these pro-teins were from plasma membrane, endoplasmic reticulum, cytoskeleton and cytosol, however, there were 21% proteins among total 647 proteins were from nucleus, mitochondria and ribosomes. Conclusion The sucrose density gradient ultra-centrifugation method is a effective method to extract lipid rafts from cerebral cortex, however, the properties of mixture should be considered.
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Objective The animal model of rheumatoid arthritis was established in Lewis rats by a single intradermal injection of pristane. Methods The degree of pathogenicity and the pathological characteristics were assayed by histiopathological techniques and joint roentgenography. Results The incidence of arthritis in rats immunized by pristane was 62.5%. Peripheral joints were mainly involved. A chronic relapsing and progressive arthritis was developed.As showed by histopathology and roentgenography, typical arthritis pathology such as synovial proliferation, articular cartilage and bone erosien were found. Conclusion Pristane induced arthritis mirrors human rheumatoid arthritis and is a very good animal model for rheumatoid arthritis.