26 research outputs found

    Extracellular Vesicle-Mediated Macrophage Activation: An Insight Into the Mechanism of Thioredoxin-Mediated Immune Activation

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    Extracellular vesicles (EVs) generated from redox active anticancer drugs are released into the extracellular environment. These EVs contain oxidized molecules and trigger inflammatory responses by macrophages. Using a mouse model of doxorubicin (DOX)-induced tissue injury, we previously found that the major sources of circulating EVs are from heart and liver, organs that are differentially affected by DOX. Here, we investigated the effects of EVs from cardiomyocytes and those from hepatocytes on macrophage activation. EVs from H9c2 rat cardiomyocytes (H9c2 EVs) and EVs from FL83b mouse hepatocytes (FL83 b EVs) have different levels of protein-bound 4-hydroxynonenal and thus different immunostimulatory effects on mouse RAW264.7 macrophages. H9c2 EVs but not FL83 b EVs induced both pro-inflammatory and anti-inflammatory macrophage activation, mediated by NFκB and Nrf-2 pathways, respectively. DOX enhanced the effects of H9c2 EVs but not FL83 b EVs. While EVs from DOX-treated H9c2 cells (H9c2 DOXEVs) suppressed mitochondrial respiration and increased glycolysis of macrophages, EVs from DOX-treated FL83b cells (FL83b DOXEVs) enhanced mitochondrial reserve capacity. Mechanistically, the different immunostimulatory functions of H9c2 EVs and FL83 b EVs are regulated, in part, by the redox status of the cytoplasmic thioredoxin 1 (Trx1) of macrophages. H9c2 DOXEVs lowered the level of reduced Trx1 in cytoplasm while FL83b DOXEVs did the opposite. Trx1 overexpression alleviated the effect of H9c2 DOXEVs on NFκB and Nrf-2 activation and prevented the upregulation of their target genes. Our findings identify EVs as a novel Trx1-mediated redox mediator of immune response, which greatly enhances our understanding of innate immune responses during cancer therapy

    Extracellular Vesicles Released After Cranial Radiation: An Insight into an Early Mechanism of Brain Injury

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    Cranial radiation is important for treating both primary brain tumors and brain metastases. A potential delayed side effect of cranial radiation is neurocognitive function decline. Early detection of CNS injury might prevent further neuronal damage. Extracellular vesicles (EVs) have emerged as a potential diagnostic tool because of their unique membranous characteristics and cargos. We investigated whether EVs can be an early indicator of CNS injury by giving C57BJ/6 mice 10 Gy cranial IR. EVs were isolated from sera to quantify: 1) number of EVs using nanoparticle tracking analysis (NTA); 2) Glial fibrillary acidic protein (GFAP), an astrocyte marker; and 3) protein-bound 4-hydroxy-2-nonenal (HNE) adducts, an oxidative damage marker. Brain tissues were prepared for immunohistochemistry staining and protein immunoblotting. The results demonstrate: 1) increased GFAP levels (p \u3c 0.05) in EVs, but not brain tissue, in the IR group; and 2) increased HNE-bound protein adduction levels (p \u3c 0.05). The results support using EVs as an early indicator of cancer therapy-induced neuronal injury

    Hydrogen cyanamide enhances MRI-measured water status in flower buds of peach (Prunus persica L.) during winter

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    Abstract Braking bud dormancy in temperate fruit species using physical and chemical agents is a challenge issue. In present study, we investigated the interaction between hydrogen cyanamide (HC) and temperature in breaking dormancy to gain a basic knowledge on water status in peach (Prunus persica L.) floral buds. The water status, relaxation time (T 2 ) and apparent diffusion coefficient (ADC), in the upper part (flower primordia and bud scales), basal part, and bud trace of flower buds were determined using the magnetic resonance imaging (MRI). Bulk water, which might flow through the bud trace, increased the water content in the basal part, and water molecular mobility as reflected by an increase in T 2 in HC-treated buds after 1 week at 5C. The HC triggers the influx of water into the bud, where the basal part exhibited the highest level of water accumulation. The study provides significant insights into the status of water in floral buds and highlights the role of HC to solve the problems of produce in temperate fruits
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