Adhesion and motility of mammalian leukocytes are essential requirements for innate and adaptive immune defense mechanisms. We show here that the guanine nucleotide exchange factor cytohesin-1, which had previously been demonstrated to be an important component of beta-2 integrin activation in lymphocytes, regulates the activation of the small GTPase RhoA in primary dendritic cells (DCs). Cytohesin-1 and RhoA are both required for the induction of chemokine-dependent conformational changes of the integrin beta-2 subunit of DCs during adhesion under physiological flow conditions. Furthermore, use of RNAi in murine bone marrow DCs (BM-DCs) revealed that interference with cytohesin-1 signaling impairs migration of wild-type dendritic cells in complex 3D environments and in vivo. This phenotype was not observed in the complete absence of integrins. We thus demonstrate an essential role of cytohesin-1/RhoA during ameboid migration in the presence of integrins and further suggest that DCs without integrins switch to a different migration mode.
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http://dx.doi.org/10.1182/blood-2008-08-176123 | DOI Listing |
Aging Cell
December 2024
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Despite advances in understanding molecular and cellular changes in the aging nervous system, the upstream drivers of these changes remain poorly defined. Here, we investigate the roles of non-neural tissues in neuronal aging, using the cutaneous PVD polymodal sensory neuron in Caenorhabditis elegans as a model. We demonstrate that during normal aging, PVD neurons progressively develop excessive dendritic branching, functionally correlated with age-related proprioceptive deficits.
View Article and Find Full Text PDFJ Nanobiotechnology
December 2024
Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, the Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, 570102, China.
Limited drug accumulation and an immunosuppressive microenvironment are the major bottlenecks in the treatment of glioblastoma multiforme (GBM). Herein, we report a copper-coordination driven brain-targeting nanoassembly (TCe6@Cu/TP5 NPs) for site-specific delivery of therapeutic agents and efficient immunotherapy by activating the cGAS-STING pathway and downregulating the expression of PD-L1. To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs.
View Article and Find Full Text PDFSci Rep
December 2024
National Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi'an, Shaanxi, China.
Glioma is the most common malignant brain tumor. Previous studies have reported that calnexin (CANX) is significantly up-regulated in a variety of malignant tumors, including glioma, but its biological function and mechanism in glioma is still unclear. In this study, differentially expressed proteins in 3 primary glioblastoma multiforme (GBM) tissues and 3 paracancer tissues were identified by liquid chromatography-tandem mass spectrometry-based proteomic and bioinformatic analysis.
View Article and Find Full Text PDFActa Biomater
December 2024
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China. Electronic address:
Effective vaccination is crucial for intervening in the COVID-19 pandemic. However, with the continuous mutation of the SARS-CoV-2, existing vaccines including subunit vaccines cannot effectively prevent virus infections. Hence, there is an urgent need to enhance the immunogenicity of existing vaccines to induce a more potent and durable immune response.
View Article and Find Full Text PDFJ Control Release
December 2024
Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China; Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai 200433, China. Electronic address:
Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 (I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation.
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