DNA vector-based Stat3-specific RNA interference （si-Stat3） blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on...DNA vector-based Stat3-specific RNA interference （si-Stat3） blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BIJ6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Star3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGFand cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling （TUNEL） assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% （P〈0.01）. Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis （up to 42%, P〈0.01）. The Stat3 downstream genes Bcl-2, VEGFand cyclin DI were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.展开更多
We report here an investigation of the X-ray eclipse transitions of the high mass X-ray binary pulsar Cen X-3 in different intensity states. The long term light curve of Cen X-3 obtained with RXTE-ASM spanning more th...We report here an investigation of the X-ray eclipse transitions of the high mass X-ray binary pulsar Cen X-3 in different intensity states. The long term light curve of Cen X-3 obtained with RXTE-ASM spanning more than 5000 d shows strong aperiodic flux variations with low and high states. We have investigated the eclipse transitions of Cen X-3 in different intensity states with data obtained from pointed observations with the more sensitive instruments onboard ASCA, BeppoSAX, XMM- Newton, Chandra and RXTE. We found a very clear trend of sharp eclipse transitions in the high state and longer transitions in the low state. This is a confirmation of this feature first observed with the RXTE-ASM but now observed with much better clarity. From the light curves obtained from several missions, it is seen that the eclipse egress in the low state starts earlier by an orbital phase of 0.02 compared to the eclipse egress in the high state indicating that the observed X-rays originate from a much larger region. We have also performed spectral analysis of the post-eclipse part of each observation. From BeppoSAX observations, the out-of-eclipse X-ray flux is found to differ by a factor of -26 during the high and low intensity states while the eclipse count rates differ by a factor of only ~ 4.7. This indicates that in the low state, there is an additional scattering medium which scatters some of the source photons towards the observer even when the neutron star is completely eclipsed. We could also resolve the three iron line components using XMM-Newton observation in the low state. By comparing the iron line equivalent width during the high and low states, it is seen that the width of the iron line is relatively large during the low state which supports the fact that significant reprocessing and scattering of X-rays takes place in the low state.展开更多
STAT （Signal Transducers and Activators of Transcription） gene family members have been revealed to be involved in cell growth and differentiation in vertebrates. Despite their physiological importance, their functi...STAT （Signal Transducers and Activators of Transcription） gene family members have been revealed to be involved in cell growth and differentiation in vertebrates. Despite their physiological importance, their functions are poorly studied at organ and systemic levels. In this study, we performed a genome-wide analysis using data from invertebrates to vertebrates to identify STAT genes and analyze their evolutionary history. Interestingly, the STAT gene family undergoes genome duplications during the evolutionary history with STAT3 homologues firstly appearing in the basal extant vertebrate, sea lamprey, suggesting its possible roles in spine formation. To investigate the functions of stat3 in fish species, TALEN technology was performed to generate mutant zebrafish lines, star3 mutant zebrafish showed no obvious defects at early developmental stage but displayed severe lateral and vertical curvature of the spine （scoliosis）, spine fracture and the incomplete bone joints with narrower junction between vertebrae at early juvenile stage, as indicated by Alizarin red and Alcian blue staining, radiography and micro-computed tomography （MicroCT） analysis. Transcriptome analysis reveals dramatic alterations in a number of genes involved in immune and infection response, skeletal development and somatic growth, especially downregulated expression of collagen gene family, in the juvenile stat3 mutant zebrafish. Moreover, most of the collagen genes were detected to have abnormal expression pattern during the formation of spine deformities in stat3 mutants. Our data reveal that stat3 is specially expressed in vertebrates and required for normal spine development and immune function in zebrafish.展开更多
基金The authors would thank Mr Qiang-Lin Duan for English usage and paper revision.This work was funded by the National Natural Science Foundation of China （No. 30801354, No. 30970791 and No. 30870921）, the Fundamental Research Funds for the Central Universities of China （No. 200810012） and the Jilin Provincial Science ＆ Technology Department, China （No. 20080154）.
文摘DNA vector-based Stat3-specific RNA interference （si-Stat3） blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BIJ6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Star3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGFand cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling （TUNEL） assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% （P〈0.01）. Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis （up to 42%, P〈0.01）. The Stat3 downstream genes Bcl-2, VEGFand cyclin DI were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.
文摘We report here an investigation of the X-ray eclipse transitions of the high mass X-ray binary pulsar Cen X-3 in different intensity states. The long term light curve of Cen X-3 obtained with RXTE-ASM spanning more than 5000 d shows strong aperiodic flux variations with low and high states. We have investigated the eclipse transitions of Cen X-3 in different intensity states with data obtained from pointed observations with the more sensitive instruments onboard ASCA, BeppoSAX, XMM- Newton, Chandra and RXTE. We found a very clear trend of sharp eclipse transitions in the high state and longer transitions in the low state. This is a confirmation of this feature first observed with the RXTE-ASM but now observed with much better clarity. From the light curves obtained from several missions, it is seen that the eclipse egress in the low state starts earlier by an orbital phase of 0.02 compared to the eclipse egress in the high state indicating that the observed X-rays originate from a much larger region. We have also performed spectral analysis of the post-eclipse part of each observation. From BeppoSAX observations, the out-of-eclipse X-ray flux is found to differ by a factor of -26 during the high and low intensity states while the eclipse count rates differ by a factor of only ~ 4.7. This indicates that in the low state, there is an additional scattering medium which scatters some of the source photons towards the observer even when the neutron star is completely eclipsed. We could also resolve the three iron line components using XMM-Newton observation in the low state. By comparing the iron line equivalent width during the high and low states, it is seen that the width of the iron line is relatively large during the low state which supports the fact that significant reprocessing and scattering of X-rays takes place in the low state.
基金supported by the Fundamental Research Funds for the Central Universities (2662015PY101)the Autonomous Project of State Key Laboratory of Freshwater Ecology and Biotechnology (2011FBZ22)the Autonomous Projects of the Institute of Hydrobiology,Chinese Academy of Sciences (Y25A17, Y45A171301)
文摘STAT （Signal Transducers and Activators of Transcription） gene family members have been revealed to be involved in cell growth and differentiation in vertebrates. Despite their physiological importance, their functions are poorly studied at organ and systemic levels. In this study, we performed a genome-wide analysis using data from invertebrates to vertebrates to identify STAT genes and analyze their evolutionary history. Interestingly, the STAT gene family undergoes genome duplications during the evolutionary history with STAT3 homologues firstly appearing in the basal extant vertebrate, sea lamprey, suggesting its possible roles in spine formation. To investigate the functions of stat3 in fish species, TALEN technology was performed to generate mutant zebrafish lines, star3 mutant zebrafish showed no obvious defects at early developmental stage but displayed severe lateral and vertical curvature of the spine （scoliosis）, spine fracture and the incomplete bone joints with narrower junction between vertebrae at early juvenile stage, as indicated by Alizarin red and Alcian blue staining, radiography and micro-computed tomography （MicroCT） analysis. Transcriptome analysis reveals dramatic alterations in a number of genes involved in immune and infection response, skeletal development and somatic growth, especially downregulated expression of collagen gene family, in the juvenile stat3 mutant zebrafish. Moreover, most of the collagen genes were detected to have abnormal expression pattern during the formation of spine deformities in stat3 mutants. Our data reveal that stat3 is specially expressed in vertebrates and required for normal spine development and immune function in zebrafish.
