Search results for "trace"
showing 10 items of 3218 documents
Regulatory effects of simvastatin and apoJ on APP processing and amyloid-beta clearance in blood-brain barrier endothelial cells
2017
Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer’s disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients. ApoJ may bind, prevent fibrillization, and enhance clearance of Aβ. We here define a connection of apoJ and cellular cholesterol home…
Ecological network analysis reveals the inter-connection between soil biodiversity and ecosystem function as affected by land use across Europe
2016
Soil organisms are considered drivers of soil ecosystem services (primary productivity, nutrient cycling, carbon cycling, water regulation) associated with sustainable agricultural production. Soil biodiversity was highlighted in the soil thematic strategy as a key component of soil quality. The lack of quantitative standardised data at a large scale has resulted in poor understanding of how soil biodiversity could be incorporated into legislation for the protection of soil quality. In 2011, the EcoFINDERS (FP7) project sampled 76 sites across 11 European countries, covering five biogeographical zones (Alpine, Atlantic, Boreal, Continental and Mediterranean) and three land-uses (arable, gra…
Dissecting the role of ADAM10 as a mediator of Staphylococcus aureus α-toxin action
2016
Staphylococcus aureus is a leading cause of bacterial infections in humans, including life-threatening diseases such as pneumonia and sepsis. Its small membrane-pore-forming α-toxin is considered an important virulence factor. By destroying cell–cell contacts through cleavage of cadherins, the metalloproteinase ADAM10 (a disintegrin and metalloproteinase 10) critically contributes to α-toxin-dependent pathology of experimental S. aureus infections in mice. Moreover, ADAM10 was proposed to be a receptor for α-toxin. However, it is unclear whether the catalytic activity or specific domains of ADAM10 are involved in mediating binding and/or subsequent cytotoxicity of α-toxin. Also, it is not k…
Collective Cell Migration in a Fibrous Environment: A Hybrid Multiscale Modelling Approach
2021
International audience; The specific structure of the extracellular matrix (ECM), and in particular the density and orientation of collagen fibres, plays an important role in the evolution of solid cancers. While many experimental studies discussed the role of ECM in individual and collective cell migration, there are still unanswered questions about the impact of nonlocal cell sensing of other cells on the overall shape of tumour aggregation and its migration type. There are also unanswered questions about the migration and spread of tumour that arises at the boundary between different tissues with different collagen fibre orientations. To address these questions, in this study we develop …
Importance of stem cell culture conditions for their derived extracellular vesicles therapeutic effect.
2021
Stem cell-derived extracellular vesicles (EVs) could be enhanced by modifying specific in vitro parameters when culturing their originating stem cells. Controlling stem cell growth conditions with physical properties, oxygen tension and media preconditioning with soluble factors may influence EVs biogenesis and EVs biological function as well. Unfortunately, many misconceptions and methodological issues have hampered the progress in understanding the biological properties of EVs. In this review we will first discuss the major concerns involved in a suitable EVs production from stem cell culture. Then, we will describe the current techniques for EV isolation, focusing on their advantages and…
Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery
2020
Cathepsin S (CatS) is a secreted cysteine protease that cleaves certain extracellular matrix proteins, regulates antigen presentation in antigen-presenting cells (APC), and promotes M2-type macrophage and dendritic cell polarization. CatS is overexpressed in many solid cancers, and overall, it appears to promote an immune-suppressive and tumor-promoting microenvironment. While most data suggest that CatS inhibition or knockdown promotes anti-cancer immunity, cell-specific inhibition, especially in myeloid cells, appears to be important for therapeutic efficacy. This makes the design of CatS selective inhibitors and their targeting to tumor-associated M2-type macrophages (TAM) and DC an attr…
Editorial for the Special Issue “Extracellular Chaperones and Related miRNA as Diagnostic Tools of Chronic Diseases”
2021
Molecular chaperones are a family of proteins that are highly conserved during phylogenesis [...]
Utilizing the nanosecond pulse technique to improve antigen intracellular delivery and presentation to treat tongue squamous cell carcinoma
2017
Background Tongue squamous cell carcinoma is the most common squamous cell carcinoma of the head and neck. Immunotherapy has great potential in the treatment of tongue squamous cell carcinoma because of its unique advantages. However, the efficacy of immunotherapy is limited by the efficiency of antigen phagocytosis by immune cells. Material and Methods We extracted dendritic cells (DCs) from human peripheral blood. Utilizing a nanosecond pulsed electric field (nsPEF), we deliver the tumour lysate protein into DCs and then incubate the DCs with PBMCs to obtain specific T cells to kill tumour cells. The biosafety of nsPEF was evaluated by the ANNEXIN V-FITC/PI kit. The efficacy of lysate pro…
AB052. P-20. Phase 2, open-label study of second-line M7824 treatment in patients with locally advanced or metastatic biliary tract cancer
2019
BACKGROUND: Transforming growth factor β (TGF-β) signaling promotes tumor immunosuppression; its inhibition in the tumor microenvironment may enhance the response to anti-PD-L1 treatment. M7824 is an innovative first-in-class bifunctional fusion protein composed of 2 extracellular domains of TGF-βRII (a TGF-β “trap”) fused to a human IgG1 mAb against PD-L1. Building upon encouraging efficacy observed in a phase 1 study, the present study will evaluate M7824 clinical benefit in patients with pretreated biliary tract cancer (BTC). METHODS: This multicenter, international trial is evaluating M7824 monotherapy in patients with locally advanced or metastatic (LA/M) BTC unselected for tumor PD-L1…
Impact of the Usher syndrome on olfaction
2015
Usher syndrome is a genetically and clinically heterogeneous disease in humans, characterized by sensorineural hearing loss, retinitis pigmentosa and vestibular dysfunction. This disease is caused by mutations in genes encoding proteins that form complex networks in different cellular compartments. Currently, it remains unclear whether the Usher proteins also form networks within the olfactory epithelium (OE). Here, we describe Usher gene expression at the mRNA and protein level in the OE of mice and showed interactions between these proteins and olfactory signaling proteins. Additionally, we analyzed the odor sensitivity of different Usher syndrome mouse models using electro-olfactogram re…