39 research outputs found

    Multiple Signaling Pathways Are Involved in the Interleukine-4 Regulated Expression of DC-SIGN in THP-1 Cell Line

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    Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) is an important pattern recognition receptor on dendritic cells (DCs), and its expression shows significant cytological and histological specificity, being interleukine-4 (IL-4) dependent. The signaling pathways through which IL-4 regulates expression of DC-SIGN are still unclear. We used phorbol 12-myristate 13-acetate- (PMA-) differentiated THP-1 cells as the in vitro model of monocyte/macrophage cells to study the signaling pathways involved in IL-4-regulated expression of DC-SIGN. We found that a high expression of DC-SIGN could be induced by IL-4 at the levels of mRNA and cell surface protein. Upregulated expression of DC-SIGN was almost completely blocked by the specific inhibitor of ERK pathway, and partly reduced by the specific inhibitors of JAK-STAT and NF-κB pathways. The activation of the three signaling pathways was directly confirmed by testing the phosphorylation of protein kinase within the cytoplasm and nucleus over time. The analysis of cis-acting elements of DC-SIGN promoter showed that the activity of DC-SIGN promoter without Ets-1 transcription factors binding site almost completely disappeared. Our results demonstrated that multiple signaling pathways are involved in IL-4 induced high expression of DC-SIGN on THP-1 cells, in which ERK pathway is the main signaling pathway and mediated by the Ets-1 transcription factors binding site

    Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans

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    The intricate interaction between spermatogonial stem cell (SSC) and testicular niche is essential for maintaining SSC homeostasis; however, this interaction remains largely uncharacterized. In this study, to characterize the underlying signaling pathways and related paracrine factors, we delineated the intercellular interactions between SSC and niche cell in both adult mice and humans under physiological conditions and dissected the niche-derived regulation of SSC maintenance under recovery conditions, thus uncovering the essential role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in SSC maintenance. We also established the clinical relevance of specific paracrine factors in human fertility. Collectively, our work on decoding the adult SSC niche serves as a valuable reference for future studies on the aetiology, diagnosis, and treatment of male infertility.</p

    RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy

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    Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation

    Characterization of Novel Reassortant Influenza A (H5N2) Viruses Isolated from Poultry in Eastern China, 2015

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    Recently, novel variants of H5 highly pathogenic avian influenza viruses (AIVs) have been frequently isolated from poultry and wild birds in Asia, Europe and North America. Live poultry markets (LPMs) play an important role in the dissemination of influenza viruses. Four H5N2 AIVs were isolated from poultry during surveillance of AIVs in LPMs in Eastern China, in 2015. Whole-genome sequencing, combined with phylogenetic and antigenic analyses were performed to characterize these viruses. These H5N2 viruses had undergone extensive reassortment resulting in two genetic groups of viruses in poultry. These viruses exhibited slightly pathogenicity in mice, and replicated without prior adaptation. The continued circulation of these novel H5N2 viruses may represent a threat to human health

    Novel Reassortant Influenza A(H5N8) Viruses in Domestic Ducks, Eastern China

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    Domestic ducks are natural reservoirs of avian influenza viruses and serve as reassortant hosts for new virus subtypes. We isolated 2 novel influenza A(H5N8) viruses from domestic ducks in eastern China, sequenced their genomes, and tested their pathogenicity in chickens and mice. Circulation of these viruses may pose health risks for humans

    High performance lithium-ion capacitors based on dynamic matching principle

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    As a new generation of energy storage devices, lithium-ion capacitors (LICs) rationally combine high energy density and high power density, providing an alternative solution for multi-functional electronic equipment and state grid system. However, the dynamic mismatch between the battery-type anode and the capacitor-type cathode seriously limits its development and application. Herein, a high performance LIC simultaneously using carbon materials derived from Ethylenediaminetetraacetic Acid Ferric Sodium Salt (EDTA-Na-Fe) was prepared. By calcination of EDTA-Na-Fe in an inert atmosphere, nitrogen-doped carbon frameworks (NCF) can be obtained which possess a high reversible capacity and excellent rate-capability. Using this NCF as the anode and cathode of the LICs, the hybrid devices with a wide voltage window of 0.5-4.0 V are obtained. The employment of the same materials as the anode and cathode can largely simplify the fabrication process. The energy density of LICs can reach 193.4 Wh·kg-1 at a power density of 225 W·kg-1. This reasonable dynamic matching strategy can be helpful for the application of LICs

    Electrochemical Voltammogram Recording for Identifying Varieties of Ornamental Plants

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    An electrochemical voltammogram recording method for plant variety identification is proposed. Electrochemical voltammograms of Vistula, Andromeda, Danuta, Armandii 'Apple Blossom,' Proteus, Hagley Hybrid, Violet Elizabeth, Kiri Te Kanawa, Regina, and Veronica's Choice were recorded using leaf extracts with two solvents under buffer solutions. The voltametric data recorded under different conditions were derived as scatter plots, 2D density patterns, and hot maps for variety identification. In addition, the voltametric data were further used for genetic relationship studies. The dendrogram deduced from the voltammograms was used as evidence for relationship study. The dendrogram deduced from voltametric data suggested the Andromeda, Danuta, Proteus, Regina, and Hagley Hybrid were closely related, while Violet Elizabeth and Veronica's Choice were closely related. In addition, Vistula and Armandii 'Apple Blossom' could be considered outliers among the varieties
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