Severe traumatic injury during long duration spaceflight: Light years beyond ATLS

Traumatic injury strikes unexpectedly among the healthiest members of the human population, and has been an inevitable companion of exploration throughout history. In space flight beyond the Earth's orbit, NASA considers trauma to be the highest level of concern regarding the probable incidence versus impact on mission and health. Because of limited resources, medical care will have to focus on the conditions most likely to occur, as well as those with the most significant impact on the crew and mission. Although the relative risk of disabling injuries is significantly higher than traumatic deaths on earth, either issue would have catastrophic implications during space flight. As a result this review focuses on serious life-threatening injuries during space flight as determined by a NASA consensus conference attended by experts in all aspects of injury and space flight

Royal jelly fatty acids modulate proliferation and cytokine production by human peripheral blood mononuclear cells

Royal jelly (RJ) fatty acids have recently been shown to possess various pharmacological and biological activities. In this work, we studied the immunomodulatory effects of 10-hydroxy-trans-2-decenoic acid (10-HDA) and 3,10-dihydroxy-decanoic acid (3,10-DDA), isolated from RJ, using a model of phytohaemagglutinin-activated human peripheral blood mononuclear cells (PBMCs). We showed that higher concentrations (500 μM) of both fatty acids inhibited the proliferation of PBMCs, and the process was followed by a decrease in the production of interleukin-2 (IL-2). 10-HDA at the concentration of 500 μM inhibited the production of IL-1β and tumor necrosis factor-α by stimulated PBMCs, whereas the same dose of 3,10-DDA had no effect on the levels of these cytokines. Regarding T helper (Th) cytokine profile, higher concentration of 10-HDA, in contrast to the lower one (50 μM), inhibited both Th1 and Th2 response, whereas Th17 response was not significantly modulated, as judged by the levels of interferon-γ, IL-5 and IL-17A in culture supernatants, respectively. Lower concentration of 3,10-DDA stimulated Th1 and Th17 responses and inhibited IL-10 production, whereas the higher dose augmented the Th2 response. In conclusion, our results showed a significant, dose-dependent, immunomodulatory effect of RJ fatty acids in vitro, which was also associated with their structure. © 2014 Springer-Verlag Berlin Heidelberg

Iron-based nanoparticles and their potential toxicity : focus on oxidative stress and apoptosis

Recently, there have been several studies indicating that iron-based nanomaterials may exhibit certain toxic properties. Compared to conventional iron and iron oxides, iron nanoparticles (FeNPs) have some unique physical and chemical traits which impact their absorption, biodistribution and elimination. Facilitated passage through biological barriers enables FeNPs to reach various tissues and cells, and interact with a variety of different compounds. Currently, most of the recent research is focused on the potential cytotoxicity of FeNPs, and its implications on cell viability and functions. Some studies suggested that, in certain cell types, FeNPs may increase levels of oxidative stress and induce generation of reactive oxygen species. Oxidative stress may be one of the most important mechanisms by which FeNPs exhibit cytotoxic effects. Some authors have also suggested that, in certain conditions, exposure to FeNPs, in combination with other factors, may lead to changes in intracellular signaling resulting in programmed cell death. In this short review, we focus on the recent research on potential cytotoxicity of iron-based nanomaterials, and the potential implications of this new knowledge in medicine, chemistry and biology

Evaluation of the immunomodulatory activities of royal jelly components in vitro

In this work the effect of different components isolated from royal jelly (RJ) was studied using an in vitro rat T-cell proliferation assay. We found that lower concentrations of MEL 174 (final water extract of RJ) and MEL 147 (3-10-dihydroxydecanoic acid) stimulated T-cell proliferation, triggered by concanavalin A (Con-A) and the process was followed by an increase in the production of interleukin-2 (IL-2). Higher concentrations of MEL 174, MEL 247 (dry powder of RJ) and MEL 138 (trans-10-hydroxydec-2-enoic acid) inhibited T-cell proliferation. The inhibition of T-cell proliferation in the presence of MEL 174 was followed by a decrease in IL-2 production, which was partly abrogated by exogenous IL-2, a decrease in nitric oxide (NO) production and increased apoptosis. In conclusion, our results showed the complexity of biological activity of RJ and suggest that its water extract possesses the most potent immunomodulatory activity in vitro. Copyright © Informa Healthcare USA, Inc

3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells

Different pharmacologically active components have been isolated from royal jelly. Some of them possess imunomodulatory activity, but the mechanisms of their effect on the immune system have not been elucidated yet. In this study we tested the effect of 3,10-dihydroxy-decanoic acid (3,10-DDA), a fatty acid isolated from royal jelly, on maturation and functions of human monocyte-derived dendritic cells (MoDCs). We showed that 3,10-DDA stimulated maturation of MoDCs by up-regulating the expression of CD40, CD54, CD86 and CD1a, and increased their allostimulatory potential in co-culture with allogeneic CD4+T cells. 3,10-DDA-treated MoDCs enhanced the production of IL-12 and IL-18, and stimulated the production of interferon-γ in co-culture with allogeneic CD4+T cells, compared to control MoDCs. In contrast, the production of IL-10 was down-regulated. In conclusion, our results suggest that 3,10-DDA stimulates maturation and Th1 polarising capability of human MoDCs in vitro, which could be beneficial for anti-tumour and anti-viral immune responses. © 2010 Elsevier Ltd. All rights reserved

Fatty acids isolated from royal jelly modulate dendritic cell-mediated immune response in vitro

Royal jelly (RJ), especially its protein components, has been shown to possess immunomodulatory activity. However, almost nothing is known about the influence of RJ fatty acids on the immune system. In this work we studied the effect of 10-hydroxy-2-decanoic acid (10-HDA) and 3,10-dihydroxy-decanoic acid (3,10-DDA), isolated from RJ, on the immune response using a model of rat dendritic cell (DC)-T-cell cocultures. Both fatty acids, at higher concentrations, inhibited the proliferation of allogeneic T cells. The effect of 10-HDA was stronger and was followed by a decrease in interleukin-2 (IL-2) production and down-regulation of IL-2 receptor expression. Spleen DC, cultivated with 10 μg/ml of fatty acids down-regulated the expression of CD86 and the production of IL-12, but up-regulated the production of IL-10. In contrast, DC, pretreated with 100 μg/ml of 3,10-DDA, up-regulated the expression of CD86 and augmented the proliferation of allogeneic T cells. The highest dose (200 μg/ml) of both fatty acids which was non-apoptotic for both T cells and DC, down-regulated the expression of MHC class II and CD86, decreased the production of IL-12 and made these DC less allostimulatory. The immunosuppressive activity of 3,10-DDA was also confirmed in vivo, using a model of Keyhole lymphet hemocyanine immunization of rats. In conclusion, our results showed the immunomodulatory activity of RJ fatty acids and suggest that DC are a significant target of their action. © 2007 Elsevier B.V. All rights reserved

Dissecting multivalent lectin-glycan interactions using polyvalent glycan-quantum dot

[[abstract]]Cross-presentation is a key function of dendritic cells (DCs), which present exogenous antigens on MHC class I molecules to prime cytotoxic T lymphocyte (CTL) responses. Here, we used synthetic mono-, di-palmitoylated peptides and non-lipidated peptide that contain CTL epitopes of HPV E7. We observed that all three peptides can be internalized by the bone marrow-derived DCs (BMDCs) but using different pathway. The mono-palmitoylated peptide can be internalized by an energyindependent pathway. The di-palmitoylated peptides internalization was facilitated by TLR2 via clathrin-mediated endocytosis. The mono-palmitoylated peptide immunization can induce T cell responses and the anti-tumor effects can be enhanced in the presence of the emulsion type adjuvant. However, the administration of di-palmitoylated peptide alone can induce anti-tumor effects through TLR2. We further demonstrated that the induction of antigen-specific CTL responses and tumor regression by dipalmitoylated peptides was transporter associated with antigen processing (TAP) independent. In addition, presentation of di-palmitoylated peptides by MHC class I molecules was blocked in the presence of an endosomal acidification inhibitor (chloroquine) or a lysosomal degradation inhibitor (Z-FL-COCHO). In summary, our data suggest that the different types of the lapidated can have different mechanisms to induce anti-tumor effects

Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells

Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physicochemical and biological properties; making them attractive for application in theranostics: However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th) 1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells. While unable to affect T cells directly, GQD impaired the differentiation and functions of monocyte-derived dendritic cells (DC), lowering their capacity to stimulate T cell proliferation, development of Thl and Th17 cells, and T-cell mediated cytotoxicity. Additionally, GQD-treated DC potentiated Th2 polarization, and induced suppressive CD4(+)CD25(high)Foxp3(+) regulatory T cells. After internalization in a dynamin-independent, cholesterol-dependent manner, GQD lowered the production of reactive oxygen species and nuclear translocation of NF-kappa B in DC. The activity of mammalian target of rapamycin (mTOR) was reduced by GQD, which correlated with the increase in transcription of autophagy genes and autophagic flux in DC. Genetic suppression of autophagy impaired the pro-tolerogenic effects of GQD on DC. Our results suggest that GQD-triggered autophagy promotes tolerogenic functions in monocyte-derived DC, which could be beneficial in inflammatory T-cell mediated pathologies, but also harmful in GQD-based anti-cancer therapy. (C) 2017 Elsevier Ltd. All rights reserved