Background：Abnormal neuronal differentiation plays an important role in central nervous system （CNS） development abnormalities such as Down syndrome （DS）,a disorder that results directly from overexpression of ge...Background：Abnormal neuronal differentiation plays an important role in central nervous system （CNS） development abnormalities such as Down syndrome （DS）,a disorder that results directly from overexpression of genes in trisomic cells.Receptor-interacting protein 140 （RIP 140） is significantly upregulated in DS brains,suggesting its involvement in DS CNS development abnormalities.However,the role of RIP140 in neuronal differentiation is still not clear.The current study aimed to investigate the effect of RIP 140 overexpression on the differentiation of neuro-2a （N2a） neuroblastoma cells,in vitro.Methods：Stably RIP 140-overexpressing N2a （N2a-RIP140） cells were used as a neurodevelopmental model,and were constructed by lipofection and overexpression validated by real-time polymerase chain reaction and Western blot.Retinoic acid （RA） was used to stimulate N2a differentiation.Combining the expression of Tuj 1 at the mRNA and protein levels,the percentage of cells baring neurites,and the number of neurites per cell body was semi-quantified to determine the effect of RIP 140 on differentiation of N2a cells.Furthermore,western blot and the ERK1/2 inhibitor U0126 were used to identify the specific signaling pathway by which RIP 140 induces differentiation of N2a cells.Statistical significance of the differences between groups was determined by one-way analysis of variance followed by the Dunnett test.Results：Compared to untransfected N2a cells RIP140 expression in N2a-RIP 140 cells was remarkably upregulated at both the mRNA and protein levels.N2a-RIP 140 cells had a significantly increased percentage of cells baring neurites,and numbers of neurites per cell,as compared to N2a cells,in the absence and presence of RA （P 〈 0.05）.In addition,Tuj l,a neuronal biomarker,was strongly upregulated in N2a-RIP140 cells （P 〈 0.05） and phosphorylated ERK1/2 （p-ERK1/2） levels in N2a-RIP140 cells were dramatically increased,while differentiation was inhibited by the ERK 1/2-specific inhibi展开更多
The comet assay (single cell gel electrophoresis assay) was used to evaluate the radiotoxicity of Augerelectron emitters in the human osteosarcoma cell line (HOS-8603). After internal exposure to 67Ga-EDTMP, the sar-c...The comet assay (single cell gel electrophoresis assay) was used to evaluate the radiotoxicity of Augerelectron emitters in the human osteosarcoma cell line (HOS-8603). After internal exposure to 67Ga-EDTMP, the sar-coma cell has been injured severely. The comet length was longer along with the increase of dose, the appearance ofcomet tail was different from that with respect to the 60Co γ-ray irradiation. DNA damage of cell was mainly due tothe radiation effect of Auger electrons. The 67Ga may be a therapeutic radionuclide with good prospect for tumortreatment and palliation of bone pain induced by metastasis.展开更多
To study the radioiodinating condition of interleukin-8(IL-8) and observe its biodistribution in mice for understanding the possibility of its application in nuclear medicine, we labelled IL-8 with 125I using Bolton-H...To study the radioiodinating condition of interleukin-8(IL-8) and observe its biodistribution in mice for understanding the possibility of its application in nuclear medicine, we labelled IL-8 with 125I using Bolton-Hunter reagent, and the distributions in mice at 5 min, 30 min, 1h, 6h and 24h after injection of 125I –IL-8 were measured. The blood clearance curve was obtained and fitted with the two-compartment model. The results showed that 125I-IL-8 was obtained with a labeling efficiency of 12.2% ±6.5% and a radiochemical purity of 91.4%±6.5%. Its spe- cific activity was 14.8 kBq/μg IL-8. A fast phase half – life T1/2 of 0.32 h and a slow phase half – life T1/2 of 8.01 h α β were calculated from the blood clearance curve. The uptakes of radioactivities in kidneys and lung had the peaks of 85.87%ID /g and 16.17%ID /g at 30 min after intravenous injection, respectively. The uptakes in liver and spleen were 12.05%ID /g and 8.97%ID /g as the maximum at 5 min after injection. The clearance in blood and other organs was fast. Except for kidneys and lung, 125I –IL-8 was less than 1%ID/ g 24 h after administration. It is concluded that radioiodinated IL-8 is a promising radiopharmaceutical in nuclear medicine, especially for imaging infection. But to enhance the labeling efficiency of radioiodinated IL-8 and to decrease its in vivo deiodination are the subjects neces- sary to be further investigated.展开更多
基金This research was supported by the grants from the National Natural Science Foundation of China （No. 30872792） and Chief Funds of the National Natural Science Foundation of China （No. 31340024）.
文摘Background：Abnormal neuronal differentiation plays an important role in central nervous system （CNS） development abnormalities such as Down syndrome （DS）,a disorder that results directly from overexpression of genes in trisomic cells.Receptor-interacting protein 140 （RIP 140） is significantly upregulated in DS brains,suggesting its involvement in DS CNS development abnormalities.However,the role of RIP140 in neuronal differentiation is still not clear.The current study aimed to investigate the effect of RIP 140 overexpression on the differentiation of neuro-2a （N2a） neuroblastoma cells,in vitro.Methods：Stably RIP 140-overexpressing N2a （N2a-RIP140） cells were used as a neurodevelopmental model,and were constructed by lipofection and overexpression validated by real-time polymerase chain reaction and Western blot.Retinoic acid （RA） was used to stimulate N2a differentiation.Combining the expression of Tuj 1 at the mRNA and protein levels,the percentage of cells baring neurites,and the number of neurites per cell body was semi-quantified to determine the effect of RIP 140 on differentiation of N2a cells.Furthermore,western blot and the ERK1/2 inhibitor U0126 were used to identify the specific signaling pathway by which RIP 140 induces differentiation of N2a cells.Statistical significance of the differences between groups was determined by one-way analysis of variance followed by the Dunnett test.Results：Compared to untransfected N2a cells RIP140 expression in N2a-RIP 140 cells was remarkably upregulated at both the mRNA and protein levels.N2a-RIP 140 cells had a significantly increased percentage of cells baring neurites,and numbers of neurites per cell,as compared to N2a cells,in the absence and presence of RA （P 〈 0.05）.In addition,Tuj l,a neuronal biomarker,was strongly upregulated in N2a-RIP140 cells （P 〈 0.05） and phosphorylated ERK1/2 （p-ERK1/2） levels in N2a-RIP140 cells were dramatically increased,while differentiation was inhibited by the ERK 1/2-specific inhibi
文摘The comet assay (single cell gel electrophoresis assay) was used to evaluate the radiotoxicity of Augerelectron emitters in the human osteosarcoma cell line (HOS-8603). After internal exposure to 67Ga-EDTMP, the sar-coma cell has been injured severely. The comet length was longer along with the increase of dose, the appearance ofcomet tail was different from that with respect to the 60Co γ-ray irradiation. DNA damage of cell was mainly due tothe radiation effect of Auger electrons. The 67Ga may be a therapeutic radionuclide with good prospect for tumortreatment and palliation of bone pain induced by metastasis.
文摘To study the radioiodinating condition of interleukin-8(IL-8) and observe its biodistribution in mice for understanding the possibility of its application in nuclear medicine, we labelled IL-8 with 125I using Bolton-Hunter reagent, and the distributions in mice at 5 min, 30 min, 1h, 6h and 24h after injection of 125I –IL-8 were measured. The blood clearance curve was obtained and fitted with the two-compartment model. The results showed that 125I-IL-8 was obtained with a labeling efficiency of 12.2% ±6.5% and a radiochemical purity of 91.4%±6.5%. Its spe- cific activity was 14.8 kBq/μg IL-8. A fast phase half – life T1/2 of 0.32 h and a slow phase half – life T1/2 of 8.01 h α β were calculated from the blood clearance curve. The uptakes of radioactivities in kidneys and lung had the peaks of 85.87%ID /g and 16.17%ID /g at 30 min after intravenous injection, respectively. The uptakes in liver and spleen were 12.05%ID /g and 8.97%ID /g as the maximum at 5 min after injection. The clearance in blood and other organs was fast. Except for kidneys and lung, 125I –IL-8 was less than 1%ID/ g 24 h after administration. It is concluded that radioiodinated IL-8 is a promising radiopharmaceutical in nuclear medicine, especially for imaging infection. But to enhance the labeling efficiency of radioiodinated IL-8 and to decrease its in vivo deiodination are the subjects neces- sary to be further investigated.
