AIM: To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tis- sue from 49 C...AIM: To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tis- sue from 49 CRC patients were analyzed. Mononuclear cells were isolated by FicolI-Hypaque density gradient centrifugation and were subjected to a flow cytometry- based immunophenotypic analysis. RESULTS: A considerable increase in the percentage of CD33+HLA-DR MDSCs was observed in the periph- eral blood (1.89% :1= 0.75%) and tumor tissues (2.99%±1.29%) of CRC patients as compared with that in theperipheral blood of healthy controls (0.54%±0.35%). This expanded CD33+HLA-DR subset exhibited imma- ture myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Fur- ther studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis (P = 0.023), whereas that in tumor tissues was cor- related with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION: Characterization of MDSCs in CRC sug- gests the clinical significance of circulating and tumor- infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.展开更多
Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of Down syndrome. Ts65 Dn mice, which are frequently used as a m...Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of Down syndrome. Ts65 Dn mice, which are frequently used as a model of Down syndrome, were intraperitoneally injected with 10 mg/kg luteolin for 4 consecutive weeks starting at 12 weeks of age. The Morris water maze test was used to evaluate learning and memory abilities, and the novel object recognition test was used to assess recognition memory. Immunohistochemistry was performed for the neural stem cell marker nestin, the astrocyte marker glial fibrillary acidic protein, the immature neuron marker DCX, the mature neuron marker NeuN, and the cell proliferation marker Ki67 in the hippocampal dentate gyrus. Nissl staining was used to observe changes in morphology and to quantify cells in the dentate gyrus. Western blot assay was used to analyze the protein levels of brain-derived neurotrophic factor(BDNF) and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2) in the hippocampus. Luteolin improved learning and memory abilities as well as novel object recognition ability, and enhanced the proliferation of neurons in the hippocampal dentate gyrus. Furthermore, luteolin increased expression of nestin and glial fibrillary acidic protein, increased the number of DCX^+ neurons in the granular layer and NeuN^+ neurons in the subgranular region of the dentate gyrus, and increased the protein levels of BDNF and p-ERK1/2 in the hippocampus. Our findings show that luteolin improves behavioral performance and promotes hippocampal neurogenesis in Ts65 Dn mice. Moreover, these effects might be associated with the activation of the BDNF/ERK1/2 pathway.展开更多
文摘AIM: To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tis- sue from 49 CRC patients were analyzed. Mononuclear cells were isolated by FicolI-Hypaque density gradient centrifugation and were subjected to a flow cytometry- based immunophenotypic analysis. RESULTS: A considerable increase in the percentage of CD33+HLA-DR MDSCs was observed in the periph- eral blood (1.89% :1= 0.75%) and tumor tissues (2.99%±1.29%) of CRC patients as compared with that in theperipheral blood of healthy controls (0.54%±0.35%). This expanded CD33+HLA-DR subset exhibited imma- ture myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Fur- ther studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis (P = 0.023), whereas that in tumor tissues was cor- related with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION: Characterization of MDSCs in CRC sug- gests the clinical significance of circulating and tumor- infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.
基金supported by the Project Funding for the Training of High Level Health Professionals in Changzhou of China,No.2016CZLJ013(to BY)Science and Technology Support Project of Changzhou of China,No.Social Development CE20175021(to BY)Application Basic Research Project of Changzhou of China,No.CJ20160036(to WBZ)
文摘Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of Down syndrome. Ts65 Dn mice, which are frequently used as a model of Down syndrome, were intraperitoneally injected with 10 mg/kg luteolin for 4 consecutive weeks starting at 12 weeks of age. The Morris water maze test was used to evaluate learning and memory abilities, and the novel object recognition test was used to assess recognition memory. Immunohistochemistry was performed for the neural stem cell marker nestin, the astrocyte marker glial fibrillary acidic protein, the immature neuron marker DCX, the mature neuron marker NeuN, and the cell proliferation marker Ki67 in the hippocampal dentate gyrus. Nissl staining was used to observe changes in morphology and to quantify cells in the dentate gyrus. Western blot assay was used to analyze the protein levels of brain-derived neurotrophic factor(BDNF) and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2) in the hippocampus. Luteolin improved learning and memory abilities as well as novel object recognition ability, and enhanced the proliferation of neurons in the hippocampal dentate gyrus. Furthermore, luteolin increased expression of nestin and glial fibrillary acidic protein, increased the number of DCX^+ neurons in the granular layer and NeuN^+ neurons in the subgranular region of the dentate gyrus, and increased the protein levels of BDNF and p-ERK1/2 in the hippocampus. Our findings show that luteolin improves behavioral performance and promotes hippocampal neurogenesis in Ts65 Dn mice. Moreover, these effects might be associated with the activation of the BDNF/ERK1/2 pathway.