Abstract:Dendritic cells (DCs) are responsible for the initiation of immune responses. Our study demonstrates a new pathway for generating a large quantity of stimulatory monocyte derived DCs (Mo-DCs) from human monocytes using anti-4-1BB Ligand (4-1BBL) mAb to trigger reverse signaling. The anti-4-1BBL-driven-Mo-DCs (DCsα-4-1BBL) not only express higher levels of CD86, CD83 and HLA-DR, when compared to the Mo-DCs matured by TNF-α, they also exhibit a unique phenotype that expresses lower levels of PD-L1. High levels of GM-CSF, M-CSF, and Flt3 Ligand(FL) were found in the anti-4-1BBL-differentiation culture. Neutralizing M-CSF, GM-CSF, and FL inhibited Mo-DC proliferation stimulated by anti-4-1BBL mAb, suggesting that M-CSF, GM-CSF, and FL are involved in cell proliferation stimulated by anti-4-1BBL. Further analysis of the DCsα-4-1BBL showed increased secretion of Th1-type cytokines IL-12 and IFN-γ, and decreased secretion of IL-10. DCsα-4-1BBL induced much stronger proliferative responses in the MLR assay when compared with DCs derived by GM-CSF. Moreover, DCsα-4-1BBL preferentially induced Th1 responses. We have further demonstrated that anti-4-1BBL antibody stimulated nuclear translocation of NF-κB from the cytoplasm in monocytes, suggesting reverse signaling by 4-1BBL is likely responsible for mediating DCs differentiation. Collectively, we have found that reverse signaling of 4-1BBL promotes the differentiation of potent Th1-inducing DCs from human monocytes.

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	1. 4-1BBL reverse signaling potently induces Dendritic Cells development from human monocytes
	Songguang Ju,Songwen Ju,Xueguang Zhang
	Basic Medicine 08 January 2009
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	Abstract:Dendritic cells (DCs) are responsible for the initiation of immune responses. Our study demonstrates a new pathway for generating a large quantity of stimulatory monocyte derived DCs (Mo-DCs) from human monocytes using anti-4-1BB Ligand (4-1BBL) mAb to trigger reverse signaling. The anti-4-1BBL-driven-Mo-DCs (DCsα-4-1BBL) not only express higher levels of CD86, CD83 and HLA-DR, when compared to the Mo-DCs matured by TNF-α, they also exhibit a unique phenotype that expresses lower levels of PD-L1. High levels of GM-CSF, M-CSF, and Flt3 Ligand(FL) were found in the anti-4-1BBL-differentiation culture. Neutralizing M-CSF, GM-CSF, and FL inhibited Mo-DC proliferation stimulated by anti-4-1BBL mAb, suggesting that M-CSF, GM-CSF, and FL are involved in cell proliferation stimulated by anti-4-1BBL. Further analysis of the DCsα-4-1BBL showed increased secretion of Th1-type cytokines IL-12 and IFN-γ, and decreased secretion of IL-10. DCsα-4-1BBL induced much stronger proliferative responses in the MLR assay when compared with DCs derived by GM-CSF. Moreover, DCsα-4-1BBL preferentially induced Th1 responses. We have further demonstrated that anti-4-1BBL antibody stimulated nuclear translocation of NF-κB from the cytoplasm in monocytes, suggesting reverse signaling by 4-1BBL is likely responsible for mediating DCs differentiation. Collectively, we have found that reverse signaling of 4-1BBL promotes the differentiation of potent Th1-inducing DCs from human monocytes.
	TO cite this article:Songguang Ju,Songwen Ju,Xueguang Zhang. 4-1BBL reverse signaling potently induces Dendritic Cells development from human monocytes[J].


	2. The role of transcription factors Sp1 and YY1 in proximal promoter region in initiation of transcription of the mu opioid receptor gene in human lymphocytes
	Hui Li,Gang Li
	Basic Medicine 30 December 2008
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	Abstract:Although previous studies have shown that the mechanism of the lymphocyte mu opioid receptor (MOR) gene expression was distinctly different from that in the central nervous system, and is involved in several disparate aspects of the immune response, its precise molecular mechanism is still undefined. In this study, we analyzed the proximal promoter region of the MOR gene in lymphocytes to identify the influences of potential trans-acting factors in activating the initiation of the expression of the MOR gene in lymphocytes. The electrophoretic mobility shift assay showed that two transcription factors, Sp1 and YY1, were able to bind the promoter region. Using sequence overlapping probes and mutation assays, we determined that the CCC sequence of Sp1 and the GGC sequence of YY1 binding elements were core sequences, and replacement of these sequences lead to substantial loss of promoter activity. Stimulation with morphine was capable of up-regulating the intracellular level of Sp1 and YY1 proteins. Chromatin immunoprecipitation assays showed that the blockage of naloxone is achieved through down-regulation of transcription factor YY1. Furthermore, coimmunoprecipitation and transfection assays confirmed that the functional interaction of Sp1 and YY1 transcription factors was a crucial step in the initiation of expression of the MOR in lymphocytes. Thus, we conclude that the cooperative interaction of Sp1 and YY1 transcription factors is the critical event triggering the initiation of transcription of the MOR gene in lymphocytes, and this finding will be helpful to understand the pharmacological effect of morphine on lymphocytes.
	TO cite this article:Hui Li,Gang Li. The role of transcription factors Sp1 and YY1 in proximal promoter region in initiation of transcription of the mu opioid receptor gene in human lymphocytes[OL].[30 December 2008] http://en.paper.edu.cn/en_releasepaper/content/27120

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	3. Comparison of Overexpression of Cbfa1 and BMP-2 on Osteoblast/Cementoblast Related Genes Expression in NIH3T3 and Dental Follicle Cells
	pan keqing,Yan Shimei,Ge Shaohua,Li Shu,Zhao Yanhong,Yang Pishan
	Basic Medicine 01 April 2008
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	Abstract:Objectives: BMP-2, one of the most widely studied factors has shown some shortcomings as a therapeutic agent to enhance periodontal regeneration, while Cbfa1 is the essential transcription factor for bone formation and tooth morphogenesis. The aim of this study was to compare the function of Cbfa1 and BMP-2 on osteoblast/cementoblast related genes expression, so as to find which was more useful for periodontal regeneration. Materials and Methods: Cbfa1 and BMP-2 recombinant retroviral plasmids were transfected into packaging cells PT67 to produce retrovirus. Then the virus was added to infect NIH3T3 and dental follicle cells (DFCs) and chosen by G418 to gain the stably overexpressed Cbfa1 or BMP-2 cells. Real-time RT-PCR, western-blotting and mineralization assay were adopted to determine and compare the effect of overexpression of Cbfa1 and BMP-2 in NIH3T3 and DFCs. Results: We successfully obtained the cells that stably overexpressed Cbfa1 or BMP-2 by retrovirus infection. In NIH3T3, both Cbfa1 and BMP-2 induced osteoblast/cementoblast related genes expression and mineral nodules formation, but Cbfa1 increased more. In DFCs, overexpression of Cbfa1 also increased osteoblast/cementoblast related genes expression and mineral nodules formation, while overexpression of BMP-2 did not seem to effect the genes expression and mineralization. Conclusions: By retroviral gene transfer approach, overexpression of Cbfa1 seems more useful for periodontal regeneration than that of BMP-2 through enhancing osteoblast/cementoblast related genes expression in vitro.
	TO cite this article:pan keqing,Yan Shimei,Ge Shaohua, et al. Comparison of Overexpression of Cbfa1 and BMP-2 on Osteoblast/Cementoblast Related Genes Expression in NIH3T3 and Dental Follicle Cells[OL].[ 1 April 2008] http://en.paper.edu.cn/en_releasepaper/content/20004


	4. Divalent metal transporter 1 upregulation is involved in the 6-hydroxydopamine induced ferrous iron influx
	Song Ning ,Jiang Hong,Wang Jun,Xie JunXia
	Basic Medicine 27 March 2008
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	Abstract:The reasons underlying the high iron content found in the substantia nigra (SN) of Parkinson’s disease (PD) are largely unknown. Based on our previous studies, we suppose that the newly discovered iron transporter, divalent metal transporter 1 (DMT1), might be involved in this SN iron accumulation process. To investigate this, we first observed the cellular expression of DMT1 in rat SN, both with the iron response element (+IRE) and without the IRE (-IRE) forms. The results showed that both forms of DMT1 were expressed on neurons, astrocytes, and microglia, but not on oligodendrocytes. We further observed the relationship between the increased iron influx and DMT1 expression in 6-hydroxydopamine (6-OHDA) treated C6 cells. 6-OHDA (10μmol/L) caused a significant increase in ferrous iron influx, with the increased expression of DMT1+IRE, both in protein and mRNA levels, while no change was observed for DMT1-IRE. To further clarify that the increased expression of DMT1 was not due to the increased intracellular iron content, C6 cells were overloaded with ferric ammonium citrate (100μg/ml). Decreased expression of both forms of DMT1 was observed. Our data suggest that DMT1 is highly expressed in rat SN in a cellular-specific manner. Increased DMT1+IRE expression is the mechanism behind ferrous iron influx induced by 6-OHDA treatment in C6 cells. This may give some evidence for the involvement of DMT1 in the iron accumulation in PD.
	TO cite this article:Song Ning ,Jiang Hong,Wang Jun, et al. Divalent metal transporter 1 upregulation is involved in the 6-hydroxydopamine induced ferrous iron influx[OL].[27 March 2008] http://en.paper.edu.cn/en_releasepaper/content/19795


	5. Peripheral Iron Dextran Induced Degeneration of Dopaminergic Neurons in Rat Substantia Nigra
	Jiang Hong ,Song Ning,Wang Jun ,Ren Li Ying,Xie Jun Xia
	Basic Medicine 27 March 2008
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	Abstract:Iron accumulation is considered to be involved in the pathogenesis of Parkinson’s disease. To demonstrate the relationship between peripheral iron overload and dopaminergic neuron loss in rat substantia nigra (SN), in the present study we used fast cyclic voltammetry, tyrosine hydroxylase (TH) immunohistochemistry, Perls’ iron staining, and high performance liquid chromatography-electrochemical detection to study the degeneration of dopaminergic neurons and increased iron content in the SN of iron dextran overloaded animals. The findings showed that peripheral iron dextran overload increased the iron staining positive cells and reduced the number of TH-immunoreactive neurons in SN. As a result, dopamine release and content, as well as its metabolites contents were decreased in caudate putamen. Even more dramatic changes were found in chronic overload group. These results suggest that peripheral iron dextran can increase the iron amount in SN, where excessive iron caused the degeneration of dopaminergic neurons. The chronic iron overload may be more destructive to dopaminergic neurons than the acute iron overload.
	TO cite this article:Jiang Hong ,Song Ning,Wang Jun , et al. Peripheral Iron Dextran Induced Degeneration of Dopaminergic Neurons in Rat Substantia Nigra[OL].[27 March 2008] http://en.paper.edu.cn/en_releasepaper/content/19780


	6. The dose distribution detection design of fragments for heavy ions therapy
	Xinjian Tan
	Basic Medicine 24 March 2008
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	Abstract:The charged ions have been used in tumor therapy instead of conventional radiation therapy since 1970’s mainly as its favorable depth profile of the relative biological effectiveness (RBE). However, the projectiles fragments produced inside patient’s body reach a region beyond the range of the primary particles, and cause needless exposure, known as ‘fragment tail’, which spoil the therapy effect seriously. The production of fragments is one of the most crucial, but not yet perfectly understood, problems to be considered when planning for the utilization of heavy ions therapy, and there is no detailed experimental description about the dose distribution it caused until now. In this paper, we introduce a method of detecting the light fragments briefly with the aim of giving a feasible way to measure the spatial dose distribution behind the Bragg peak or Spread out Bragg peak (SOBP) using the CR-39 solid state nuclear track detector, the HSP-1000 microscope system and the PitFit track measurement analysis software.
	TO cite this article:Xinjian Tan. The dose distribution detection design of fragments for heavy ions therapy[OL].[24 March 2008] http://en.paper.edu.cn/en_releasepaper/content/19622


	7. Intragastric Administration of Evodiamine Reduces NPY and AGRP Gene Expression in The Hypothalamus and Decreases Food Intake in Rats
	Jinghong Shi,Jianqun Yan,Qi Lei,Junjie Zhao,Ke Chen,Dejun Yang,Xiaolin Zhao
	Basic Medicine 28 January 2008
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	Abstract:Evodiamine (Evo), an alkaloidal component extracted from the fruit of Evodiae fructus (Evodia rutaecarpa Benth., Rutaceae), decreases the body weight of rats through a poorly defined mechanism. The hypothalamus is responsible for controlling food intake and energy expenditure. We postulate that Evo mediates this activity by modulating feeding-related peptides in the hypothalamus. We investigated the effects of Evo on food intake, body weight and the mRNA expression of hypothalamic NPY, AGRP, Pmch, POMC, CART, and MC4R, in male rats. Evo (40 mg/kg or 4 mg/kg) was intragastrically administrated for 25 days, and the food intake and body weight of rats were recorded daily. Blood samples were collected for leptin radioimmunoassay (RIA). Real-Time PCR was used to analyze the mRNA expression. Our results show that intragastric administration of Evo (40 mg/kg) inhibits food intake, decreases body weight and reduces the mRNA expression of NPY and AGRP in the hypothalamus, while it increases the circulating level of leptin. Our results indicate that Evo decreases food intake, and therefore body weight, partly by down-regulating NPY and AGRP mRNA expression in the hypothalamus.
	TO cite this article:Jinghong Shi,Jianqun Yan,Qi Lei, et al. Intragastric Administration of Evodiamine Reduces NPY and AGRP Gene Expression in The Hypothalamus and Decreases Food Intake in Rats[OL].[28 January 2008] http://en.paper.edu.cn/en_releasepaper/content/18417


	8. Overexpression of Cbfa1 Enhances Differentiation of Dental Follicle Cells into Cementoblasts
	pan keqing,Sun Qinfeng,Ge Shaohua,Li Shu,Wang Yan,Yang Pishan
	Basic Medicine 30 December 2007
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	Abstract:Core binding factor α1 (Cbfa1) is a runt domain transcription factor that is essential for bone formation and tooth development. It is hypothesized that forced expression of Cbfa1 in dental follicle cells (DFCs) can stimulate DFCs differentiation into cementoblast-like cells in vitro. In this study we investigated the function of Cbfa1 on DFCs by retroviral system, real-time RT-PCR, Western blot and mineralization assay. Real-time PT-PCR analysis indicated that cementoblast-related genes were expressed in DFCs, including osteopontin, type I collagen, bone sialoprotein, osteocalcin and cementum attachment protein, cementum-derived protein. Overexpression of Cbfa1 in DFCs enhanced the expression of these genes. Mineralization assay also showed that Cbfa1 increased the mineralization nodules formation. The results suggest that Cbfa1 plays an important role in the differentiation of DFCs into cementoblast-like cells by increasing the expression of cementoblast-related genes.
	TO cite this article:pan keqing,Sun Qinfeng,Ge Shaohua, et al. Overexpression of Cbfa1 Enhances Differentiation of Dental Follicle Cells into Cementoblasts [OL].[30 December 2007] http://en.paper.edu.cn/en_releasepaper/content/17600


	9. Golgi apparatus localization of ZNT7 in the mouse cerebellum
	Hui-Ling Gao,Xin Wang,Zhihong Chi,Liping Huang,Zhanyou Wang
	Basic Medicine 30 December 2007
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	Abstract:The cerebellum contains a significant amount of zinc ions. However, little is known about zinc homeostasis in the cerebellum. We have recently reported that four members of the zinc transporter (ZNT) family, ZNT1, ZNT3, ZNT4, and ZNT6, are abundantly expressed in the mouse cerebellum. In the present study, we reported that ZNT7 was present throughout the cerebellar cortex. ZNT7 immunoreactivity was predominately present in the somas and primary dendrites of the Purkinje cells. ZNT7 was also present in the Bergmann glial cell bodies as well as their radial processes, which extended into the molecular cell layer. Confocal immunofluorescence results demonstrated that the expression of ZNT7 overlapped with that of TGN38 in the somas of the Purkinje cells and granule cells. Immuno-electron microscopic study showed that ZNT7 was localized to the membrane of the Golgi apparatus in the somas of the Purkinje cells, Bergmann glial cells, and granule cells. Western blot analysis demonstrated that a considerable amount of ZNT7 was expressed in the cerebellum compared to the hippocampus. In addition, zinc autometallographic staining revealed that chelatable zinc was predominately distributed in the Bergmann glial cell bodies and their radial processes. These findings suggest a significant role of ZNT7 in zinc homeostasis in the mouse cerebellum.
	TO cite this article:Hui-Ling Gao,Xin Wang,Zhihong Chi, et al. Golgi apparatus localization of ZNT7 in the mouse cerebellum[OL].[30 December 2007] http://en.paper.edu.cn/en_releasepaper/content/17595


	10. Time–Frequency Coding via Wavelets Analysis for Bursting Spikes of Neuron Firing
	Xin Tian,Xinling Geng
	Basic Medicine 28 December 2007
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	Abstract:Bursting (spikes) shows very complex dynamics of firing activities of the neurons. The aim of this study is to investigate the coding details in time-frequency domain for bursting spikes using wavelet analysis, which will give a combinative neural code from both time and frequency domains. Data in this study is two types of the spikes: bursting and spiking simulatied from Chay model via 4-order R-K algorithm under different tasking conditions. The interspike intervals (ISI) are obtained through the spike series used for the neural coding. Mexican Hat (‘mexh’) wavelet is selected as mother wavelet used in this study. Neural coding of bursting under a 5-scale decomposition is performed and compared to that from temporal coding. The results of this study have demonstrated that time-frequency coding might be a more useful approach,and provide more details to neural coding for the bursting spikes than rate coding and temporal coding.
	TO cite this article:Xin Tian,Xinling Geng . Time–Frequency Coding via Wavelets Analysis for Bursting Spikes of Neuron Firing[OL].[28 December 2007] http://en.paper.edu.cn/en_releasepaper/content/17514

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