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      International Journal of Nanomedicine (submit here)

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      Nanonized black soybean enhances immune response in senescence-accelerated mice

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          Abstract

          Soy isoflavones may have applications in cancer prevention and anti-inflammation, therefore this study was conducted to investigate the effect of dietary supplementation with black soybean on the immune response in the senescence-accelerated-prone mice (SAMP8) and -resistant mice (SAMPR1, as controls). The mechanism of isoflavones was also investigated. Six-month-old male SAMP8 and SAMR1 mice were divided into the control groups and experimental groups supplemented with nanonized (Nano-soy) or microparticled (Micro-soy) black soybeans (n = 8/group), respectively for 12 weeks. Human peripheral blood mononuclear cells (PBMC) and murine splenocytes were stimulated with mitogens and cytokines were determined by reverse transcriptase-polymerase chain reaction and/or ELISA. The results showed that body weight, food intake, and relative weights of organs did not differ among the SAMP8 control and experimental groups. Isoflavone (daidzin and genistin) intake was higher in the Nano-soy group than the Micro-soy group. The lymphoproliferation and production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in the Nano-soy group had a significantly higher (P < 0.05) than those in the control and Micro-soy groups. The Nano-soy supplemented mice reached these cytokine levels similar to SAMR1 mice. This result was consistent with the in vitro data that daidzein (a metabolite of daidzin), at a concentration of 10 μM, increased IL-2, IL-4, and IFN-γ production from phytohemagglutinin-stimulated PBMC (P < 0.05). However at higher concentrations (> 50 μM), daidzein only reduced IL-10 and IFN-γ levels, whereas genistein reduced levels of the IL-2, IL-4, IL-10, IFN-γ mRNA and protein and these results suggest that the Nano-soy supplementation improved immune response in SAMP8 mice which may be attributable to higher daidzin content in the black soybean preparation.

          Most cited references31

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          Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus

          A diverse T cell repertoire is essential for a vigorous immune response to new infections, and decreasing repertoire diversity has been implicated in the age-associated decline in CD8 T cell immunity. In this study, using the well-characterized mouse influenza virus model, we show that although comparable numbers of CD8 T cells are elicited in the lung and lung airways of young and aged mice after de novo infection, a majority of aged mice exhibit profound shifts in epitope immunodominance and restricted diversity in the TCR repertoire of responding cells. A preferential decline in reactivity to viral epitopes with a low naive precursor frequency was observed, in some cases leading to “holes” in the T cell repertoire. These effects were also seen in young thymectomized mice, consistent with the role of the thymus in maintaining naive repertoire diversity. Furthermore, a decline in repertoire diversity generally correlated with impaired responses to heterosubtypic challenge. This study formally demonstrates in a mouse infection model that naturally occurring contraction of the naive T cell repertoire can result in impaired CD8 T cell responses to known immunodominant epitopes and decline in heterosubtypic immunity. These observations have important implications for the design of vaccine strategies for the elderly.
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            Interleukin 2, but Not Other Common γ Chain–Binding Cytokines, Can Reverse the Defect in Generation of Cd4 Effector T Cells from Naive T Cells of Aged Mice

            Development of effectors from naive CD4 cells occurs in two stages. The early stage involves activation and limited proliferation in response to T cell receptor (TCR) stimulation by antigen and costimulatory antigen presenting cells, whereas the later stage involves proliferation and differentiation in response to growth factors. Using a TCR-transgenic (Tg+) model, we have examined the effect of aging on effector generation and studied the ability of γc signaling cytokines to reverse this effect. Our results indicate that responding naive CD4 cells from aged mice, compared with cells from young mice, make less interleukin (IL)-2, expand poorly between days 3 to 5, and give rise to fewer effectors with a less activated phenotype and reduced ability to produce cytokines. When exogenous IL-2 or other γc signaling cytokines are added during effector generation, the Tg+ cells from both young and aged mice proliferate vigorously. However, IL-4, IL-7, and IL-15 all fail to restore efficient effector production. Only effectors from aged mice generated in the presence of IL-2 are able to produce IL-2 in amounts equivalent to those produced by effectors generated from young mice, suggesting that the effect of aging on IL-2 production is reversible only in the presence of exogenous IL-2.
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              Markers to measure immunomodulation in human nutrition intervention studies.

              Normal functioning of the immune system is crucial to the health of man, and diet is one of the major exogenous factors modulating individual immunocompetence. Recently, nutrition research has focused on the role of foods or specific food components in enhancing immune system responsiveness to challenges and thereby improving health and reducing disease risks. Assessing diet-induced changes of immune function, however, requires a thorough methodological approach targeting a large spectrum of immune system parameters. Currently, no single marker is available to predict the outcome of a dietary intervention on the resistance to infection or to other immune system-related diseases. The present review summarises the immune function assays commonly used as markers in human intervention studies and evaluates their biological relevance (e.g. known correlation with clinically relevant endpoints), sensitivity (e.g. within- and between-subject variation), and practical feasibility. Based on these criteria markers were classified into three categories with high, medium or low suitability. Vaccine-specific serum antibody production, delayed-type hypersensitivity response, vaccine-specific or total secretory IgA in saliva and the response to attenuated pathogens, were classified as markers with high suitability. Markers with medium suitability include natural killer cell cytotoxicity, oxidative burst of phagocytes, lymphocyte proliferation and the cytokine pattern produced by activated immune cells. Since no single marker allows conclusions to be drawn about the modulation of the whole immune system, except for the clinical outcome of infection itself, combining markers with high and medium suitability is currently the best approach to measure immunomodulation in human nutrition intervention studies. It would be valuable to include several immune markers in addition to clinical outcome in future clinical trials in this area, as there is too little evidence that correlates markers with global health improvement.
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                Author and article information

                Journal
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2009
                2009
                1 April 2009
                : 4
                : 27-35
                Affiliations
                [1 ]Departments of Food and Nutrition and
                [2 ]Applied Mathematics, Providence University, Taichung;
                [3 ]Graduate Institutes of Veterinary Pathology and
                [4 ]Medical Technology, National Chung Hsing University, Taichung, Taiwan;
                [5 ]Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan;
                [6 ]These authors have contributed equally to this work
                Author notes
                Correspondence: Kee-Ching Jeng, Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan, Tel +88 64 2359 2525 Ext. 4038, Fax +88 64 2359 2705, Email kcjengmr@ 123456vghtc.gov.tw
                Article
                ijn-4-027
                2720740
                19421368
                a882515a-bac8-4d09-8a00-839dadcf4d1e
                © 2009 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Original Research

                Molecular medicine
                nanonized black soybean,cytokines,senescence accelerated mice,splenocytes,peripheral blood mononuclear cells

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