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Wang J Zhao W Cheng L Guo M Li D Li X Tan Y Ma S Li S Yang Y Chen L Wang S 《Journal of immunology (Baltimore, Md. : 1950)》2010,185(12):7654-7662
Chronic hepatitis B virus (HBV) infection is characterized by sustained liver inflammation with an influx of lymphocytes, which contributes to the development of cirrhosis and hepatocellular carcinoma. The mechanisms underlying this immune-mediated hepatic pathogenesis remain ill defined. We report in this article that repetitive infusion of anti-CD137 agonist mAb in HBV-transgenic mice closely mimics this process by sequentially inducing hepatitis, fibrosis, cirrhosis, and, ultimately, liver cancer. CD137 mAb initially triggers hepatic inflammatory infiltration due to activation of nonspecific CD8(+) T cells with memory phenotype. CD8(+) T cell-derived IFN-γ plays a central role in the progression of chronic liver diseases by actively recruiting hepatic macrophages to produce fibrosis-promoting cytokines and chemokines, including TNF-α, IL-6, and MCP-1. Importantly, the natural ligand of CD137 was upregulated significantly in circulating CD14(+) monocytes in patients with chronic hepatitis B infection and closely correlated with development of liver cirrhosis. Thus, sustained CD137 stimulation may be a contributing factor for liver immunopathology in chronic HBV infection. Our studies reveal a common molecular pathway that is used to defend against viral infection but also causes chronic hepatic diseases. 相似文献
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Deying Ma Kexin Zhang Mingyue Zhang Shengnan Xin Xiaoli Liu Zongxi Han Yuhao Shao Shengwang Liu 《PloS one》2012,7(10)
In the current study, five novel avian β-defensins (AvBDs) were identified and characterized in tissues from Peking ducks (Anas platyrhynchos). The nucleotide sequences of these cDNAs comprised 198 bp, 182 bp, 201 bp, 204 bp, and 168 bp, and encoded 65, 60, 66, 67, and 55 amino acids, respectively. Homology, characterization and comparison of these genes with AvBD from other avian species confirmed that they were Apl_AvBD1, 3, 5, 6, and 16. Recombinant AvBDs were produced and purified by expressing these genes in Escherichia coli. In addition, peptides were synthesized according to the respective AvBD sequences. Investigation of the antibacterial activity of the Apl_AvBDs showed that all of them exhibited antibacterial activity against all 12 bacteria investigated (P<0.05 or P<0.01). In addition, the antibacterial activity of all of the AvBDs against M. tetragenus and P. multocida decreased significantly in the presence of 150 mM NaCl (P<0.01). None of the AvBDs showed hemolytic activity. Consistent with their broad-spectrum antibacterial activity, the five novel Apl_AvBDs inhibited replication of duck hepatitis virus (DHV) in vitro significantly (P<0.05). The mRNA expression of all five Apl_AvBD in most tissues, including immune organs and the liver, was upregulated in response to DHV infection at different time points. These findings provide evidence that these defensins activate the immune response to combat microbial infection. 相似文献
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Grace X. Ma Steve Shive Yin Tan Wanzhen Gao Joanne Rhee Micah Park Jaesool Kim Jamil I. Toubbeh 《Cancer epidemiology》2009,33(5):381-386
Background: Despite evidence of a decline in both incidence and prevalence of colorectal cancer nationwide, it remains the second most commonly diagnosed cancer and the third highest cause of mortality among Asian Americans, including Korean Americans. This community-based and theoretically guided study evaluated a culturally appropriate intervention program that included a bilingual cancer educational program among Korean Americans including information on CRC risks, counseling to address psychosocial and access barriers, and patient navigation assistance. Methods: A two-group quasi-experimental design with baseline and post-intervention assessment and a 12-month follow-up on screening was used in the study. Korean Americans (N = 167) were enrolled from six Korean churches. The intervention group received culturally appropriate intervention program addressing accessibility and psychosocial barriers, and navigation assistance for screening. The control group received general health education that included cancer-related health issues and screening. Results: There was a significant difference (p < 0.05) between the post-intervention and control groups in awareness of CRC risk factors. There was also a significant improvement in the pre–post across HBM measures in the intervention group for perceived susceptibility (p < 0.05) and benefits and barriers to screening (p < 0.001). At baseline, 13% of participants in the intervention group and 10% in control group reported having had a CRC cancer screening test in the previous year. At the 12-month post-intervention follow-up, 77.4% of participants in the intervention group had obtained screening compared to 10.8% in the control group. Conclusion: While health disparities result from numerous factors, a culturally appropriate and church-based intervention can be highly effective in increasing knowledge of and access to, and in reducing barriers to CRC screening among underserved Koreans. 相似文献
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Maïga O Philippe M Kotelevets L Chastre E Benadda S Pidard D Vranckx R Walch L 《The FEBS journal》2011,278(15):2655-2665
Human disc-large homolog (hDlg), also known as synapse-associated protein 97, is a scaffold protein, a member of the membrane-associated guanylate kinase family, implicated in neuronal synapses and epithelial-epithelial cell junctions whose expression and function remains poorly characterized in most tissues, particularly in the vasculature. In human vascular tissues, hDlg is highly expressed in smooth muscle cells (VSMCs). Using the yeast two-hybrid system to screen a human aorta cDNA library, we identified mitogen-activated protein/extracellular signal-responsive kinase (ERK) kinase (MEK)2, a member of the ERK cascade, as an hDlg binding partner. Site-directed mutagenesis showed a major involvement of the PSD-95, disc-large, ZO-1 domain-2 of hDlg and the C-terminal sequence RTAV of MEK2 in this interaction. Coimmunoprecipitation assays in both human VSMCs and human embryonic kidney 293 cells, demonstrated that endogenous hDlg physically interacts with MEK2 but not with MEK1. Confocal microscopy suggested a colocalization of the two proteins at the inner layer of the plasma membrane of confluent human embryonic kidney 293 cells, and in a perinuclear area in human VSMCs. Additionally, hDlg also associates with the endoplasmic reticulum and microtubules in these latter cells. Taken together, these findings allow us to hypothesize that hDlg acts as a MEK2-specific scaffold protein for the ERK signaling pathway, and may improve our understanding of how scaffold proteins, such as hDlg, differentially tune MEK1/MEK2 signaling and cell responses. 相似文献