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991.
Young Rae Ji Hei Jung Kim Dong Hun Yu Ki Beom Bae Seo Jin Park Si Jun Park Woo Young Jang Min-Cheol Kang Jain Jeong Yong Hun Sung Minjee Choi Taejun Park Taesun Park Jong Won Yun Hyun-Shik Lee Sanggyu Lee Myoung Ok Kim Zae Young Ryoo 《Biochemical and biophysical research communications》2014
Chronic hepatitis is a major cause of liver cancer, so earlier treatment of hepatitis might be reducing liver cancer incidence. Hepatitis can be induced in mice by treatment with Concanavalin A (Con A); the resulting liver injury causes significant CD4+ T cell activation and infiltration. In these T cells, Roquin, a ring-type E3 ubiquitin ligase, is activated. To investigate the role of Roquin, we examined Con A-induced liver injury and T cell infiltration in transgenic (Tg) mice overexpressing Roquin specifically in T cells. In Roquin Tg mice, Con A treatment caused greater increases in both the levels of liver injury enzymes and liver tissue apoptosis, as revealed by TUNEL and H&E staining, than wild type (WT) mice. Further, Roquin Tg mice respond to Con A treatment with greater increases in the T cell population, particularly Th17 cells, though Treg cell counts are lower. Roquin overexpression also enhances increases in pro-inflammatory cytokines, including IFN-γ, TNF-α and IL-6, upon liver injury. Furthermore, Roquin regulates the immune response and apoptosis in Con A induced hepatitis via STATs, Bax and Bcl2. These findings suggest that over-expression of Roquin exacerbates T-cell mediated hepatitis. 相似文献
992.
Xiaoyong Dai Cuizan Cai Fei Xiao Yaoling Xiong Yadong Huang Qihao Zhang Qi Xiang Guofeng Lou Mengyang Lian Zhijian Su Qing Zheng 《Biochemical and biophysical research communications》2014
It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182–188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blocked the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer. 相似文献
993.
Bo Zhang Jianxin Dai Huaqing Wang Huafeng Wei Jian Zhao Yajun Guo Kexing Fan 《Biochemical and biophysical research communications》2014
Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorption through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases. 相似文献
994.
Xiaoju Huang Jiajia Xu Mingjian Huang Jiao Li Liming Dai Kerong Dai Xiaoling Zhang 《Biochemical and biophysical research communications》2014
Cartilage formation during both embryonic development and bone repairing processes involves mesenchymal stem cells (MSCs) differentiation. Wnt/β-catenin signaling pathway inhibits early chondrogenesis and is down-regulated during Transforming growth factor-β1 (TGF-β1)-induced chondrogenesis. However, the regulatory molecules that participate in the process is unknown. This study was designed to investigate the underlying mechanisms that down-regulate Wnt/β-catenin pathway during chondrogenesis. TGF-β1-induced micromass cultures of C3H10T1/2 were used as chondrocyte differentiation model. Gene expression profile was detected by realtime-PCR. Regulatory role of HDAC1 on β-catenin was investigated by luciferase assay, chromatin immunoprecipitation (ChIP) assay, co-immunoprecipitation (Co-IP) assay and in vitro ubiquitination assay. In this study, we showed that HDAC1 was induced and suppressed β-catenin gene expression through direct binding to its promoter. Besides, HDAC1 could also interact with deacetylate β-catenin protein through its deacetylase domain, which causes degradation of β-catenin. Our results indicate that HDAC1 plays an important role in chondrogenesis and may represent a therapeutic target for modulation of cartilage development. 相似文献
995.
Chengzhi Liu Liangyan Wang Tao Li Lin LinShang Dai Bing Tian Yuejin Hua 《Biochemical and biophysical research communications》2014
Response and defense systems against reactive oxygen species (ROS) contribute to the remarkable resistance of Deinococcus radiodurans to oxidative stress induced by oxidants or radiation. However, mechanisms involved in ROS response and defense systems of D. radiodurans are not well understood. Fur family proteins are important in ROS response. Only a single Fur homolog is predicted by sequence similarity in the current D. radiodurans genome database. Our bioinformatics analysis demonstrated an additional guanine nucleotide in the genome of D. radiodurans that is not in the database, leading to the discovery of another Fur homolog DrPerR. Gene disruption mutant of DrPerR showed enhanced resistance to hydrogen peroxide (H2O2) and increased catalase activity in cell extracts. Real-time PCR results indicated that DrPerR functions as a repressor of the catalase gene katE. Meanwhile, derepression of dps (DNA-binding proteins from starved cells) gene under H2O2 stress by DrPerR point to its regulatory role in metal ions hemostasis. Thus, DrPerR might function as a Fur homolog protein which is involved in ROS response and defense. These results help clarify the complicated regulatory network that responds to ROS stress in D. radiodurans. 相似文献
996.
997.
Nan Zhang Zhentai Han Guiling Sun Angela Hoffman Iain W. Wilson Yanfang Yang Qian Gao Jianqiang Wu Dan Xie Jungui Dai Deyou Qiu 《Biochemical and biophysical research communications》2014
Taxol is a well-known effective anticancer compound. Due to the inability to synthesize sufficient quantities of taxol to satisfy commercial demand, a biotechnological approach for a large-scale cell or cell-free system for its production is highly desirable. Several important genes in taxol biosynthesis are currently still unknown and have been shown to be difficult to isolate directly from Taxus, including the gene encoding taxoid 9α-hydroxylase. Ginkgo biloba suspension cells exhibit taxoid hydroxylation activity and provides an alternate means of identifying genes encoding enzymes with taxoid 9α-hydroxylation activity. Through analysis of high throughput RNA sequencing data from G. biloba, we identified two candidate genes with high similarity to Taxus CYP450s. Using in vitro cell-free protein synthesis assays and LC–MS analysis, we show that one candidate that belongs to the CYP716B, a subfamily whose biochemical functions have not been previously studied, possessed 9α-hydroxylation activity. This work will aid future identification of the taxoid 9α-hydroxylase gene from Taxus sp. 相似文献
998.
Eric J. Yearley Paul D. Godfrin Tatiana Perevozchikova Hailiang Zhang Peter Falus Lionel Porcar Michihiro Nagao Joseph E. Curtis Pradad Gawande Rosalynn Taing Isidro E. Zarraga Norman J. Wagner Yun Liu 《Biophysical journal》2014
Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions. 相似文献
999.
1000.
Chun Tang Yun Li Xiaojun Lin Jinghua Ye Weinian Li Zhixiang He Fangfei Li Xiaoyan Cai 《Cellular immunology》2014
Tumor necrosis factor (TNF)-α is one of the major proinflammatory mediators of rheumatic arthritis (RA); the regulatory factors for TNF-α release is not fully understood. This study aims to investigate the role of prolactin receptor (PRLR) activation in regulating the expression and release of TNF-α from CD14+ monocytes. The results showed that the expression of PRLR was detectable in CD14+ monocytes of healthy subjects, which was markedly increased in RA patients. Exposure to PRL in the culture increased the expression and release of TNF-α from CD14+ monocytes, which was abolished by the PRLR gene silencing or blocking the mitogen activated protein (MAPK) pathway. We conclude that exposure to PRL increases TNF-α release from CD14+ monocytes of RA patients, which can be abolished by PRLR gene silencing or treating with MAPK inhibitor. 相似文献