25 research outputs found

    Artificially Cloaked Viral Nanovaccine for Cancer Immunotherapy

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    Virus-based cancer vaccines are nowadays considered an interesting approach in the field of cancer immunotherapy, despite the observation that the majority of the immune responses they elicit are against the virus and not against the tumor. In contrast, targeting tumor associated antigens is effective, however the identification of these antigens remains challenging. Here, we describe ExtraCRAd, a multi-vaccination strategy focused on an oncolytic virus artificially wrapped with tumor cancer membranes carrying tumor antigens. We demonstrate that ExtraCRAd displays increased infectivity and oncolytic effect in vitro and in vivo. We show that this nanoparticle platform controls the growth of aggressive melanoma and lung tumors in vivo both in preventive and therapeutic setting, creating a highly specific anti-cancer immune response. In conclusion, ExtraCRAd might serve as the next generation of personalized cancer vaccines with enhanced features over standard vaccination regimens, representing an alternative way to target cancer.Peer reviewe

    Influence of Cell Membrane Wrapping on the Cell-Porous Silicon Nanoparticle Interactions

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    Biohybrid nanosystems represent the cutting-edge research in biofunctionalization of micro- and nano-systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane-coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell-specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage-mediated uptake

    Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

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    Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases.Peer reviewe

    Decreased surface and bottom salinity and elevated bottom temperature in the Northern Baltic Sea over the past six decades

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    Highlights ‱ Changes in northern Baltic Sea temperature and salinity in 1957–2021 were investigated ‱ Temperatures in the near-bottom layer increased by 0.75–2.9 °C (0.013–0.115 °C a−1) since the 1960's ‱ Surface layer salinities declined by 0.31–1.14 units (0.005–0.019 a−1) since the 1960's ‱ Varying trends occurred in bottom salinity; declines by 0.35–1.45 units (0.007–0.025 a−1) occurred at 19 out of 33 locations Abstract Temperature and salinity are key factors in controlling marine habitats and gas fluxes. Finnish and Swedish temperature and salinity monitoring data from the northern Baltic Sea since the 1960s, and Argo buoy data from the eastern Gotland Basin and the Bothnian Sea from 2012 to 2021 were examined using linear trend analysis. Since the 1960's near-bottom temperature has increased by 0.75–2.9 °C (0.013–0.115 °C/a) and surface salinity declined by 0.31–1.14 units (0.005–0.019/a). Surface temperature trends at monitoring stations were negative (16 cases out of 33) but deemed unreliable. Near-bottom salinity has declined by 0.35–1.45 units (0.007–0.025/a), except in the northern Baltic Proper and the central-eastern Gulf of Finland. Most rapid increases in near-bottom temperature have occurred after 1993, especially in the northern Baltic Proper and the Gulf of Finland. Argo data corroborated declining surface salinity in the eastern Gotland Basin, increasing deep-water temperature in the eastern Gotland Basin and the Bothnian Sea and increasing deep-water salinity in the eastern Gotland Basin. Argo data from 2013 to 2021 indicated deep-water temperature increase in the Gotland basin was more rapid than the concomitant salinity increase and is probably related to global change

    Smad3 -signalling and Th2 cytokines in normal mouse airways and in a mouse model of asthma

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    <p>This study investigates the role of Smad3 signalling for the T-helper2 (Th2) cytokine homeostasis in normal lungs and in a mouse model of asthma.</p> <p>We used mice deficient for Smad3, a central part of the major signal transduction pathway for TGF-&#946; and other related cytokines, and a mouse model for allergic asthma with ovalbumin (OVA) as the antigen.</p> <p>Compared to wild type mice, naive (unmanipulated) Smad3-/- mice exhibited significantly increased levels of proinflammatory cytokines and IL-4 as well as the Th2 associated transcription factor GATA-3 in the lung tissue and bronchoalveolar lavage (BAL). In the asthma model, mucin secretion and airway hyperresponsiveness (AHR) after allergen exposure was significantly increased in the Smad3-/- mice as compared to wild type (WT) mice. IL-4 levels in Smad3-/- were similar to those encountered in WT mice but IL-13 levels were decreased in the airways of OVA sensitized Smad3-/- mice compared to corresponding WT mice.</p> <p>The results indicate that a lack of Smad3 dependent signalling in the normal state will lead to an increase in the GATA-3 levels and as a result of this the levels of IL-4 increase. However, the lack of Smad3 also seems to inhibit expression of some cytokines, especially IL-13. Our results also indicate that in the inflammatory state TGF-&#946; or related cytokines functions to counterbalance the effects of IL-4 rather than to critically regulate its expression.</p
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