Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs. © 2011 Yang et al

Reading Between the (Spectral) Lines: Magellan/IMACS spectroscopy of the Ultra-faint Dwarf Galaxies Eridanus IV and Centaurus I

We present a spectroscopic analysis of Eridanus IV (Eri IV) and Centaurus I (Cen I), two ultra-faint dwarf galaxies of the Milky Way. Using IMACS/Magellan spectroscopy, we identify 28 member stars of Eri IV and 34 member stars of Cen I. For Eri IV, we measure a systemic velocity of $v_{sys} = -31.5^{+1.3}_{-1.2}\:\mathrm{km\:s^{-1}}$ and velocity dispersion $\sigma_{v}= 6.1^{+1.2}_{-0.9}\:\mathrm{km\:s^{-1}}$. Additionally, we measure the metallicities of 16 member stars of Eri IV. We find a metallicity of $\mathrm{[Fe/H]}=-2.87^{+0.08}_{-0.07}$ and resolve a dispersion of $\sigma_{\mathrm{[Fe/H]}} = 0.20\pm0.09$. The mean metallicity is marginally lower than all other known ultra-faint dwarf galaxies, making it one of the most metal-poor galaxies discovered thus far. Eri IV also has a somewhat unusual right-skewed metallicity distribution. For Cen I, we find a velocity $v_{sys} = 44.9\pm0.8\:\mathrm{km\:s^{-1}}$ and velocity dispersion $\sigma_{v} = 4.2^{+0.6}_{-0.5} \:\mathrm{km\:s^{-1}}$. We measure the metallicities of 27 member stars of Cen I, and find a mean metallicity $\mathrm{[Fe/H]} = -2.57\pm0.08$ and metallicity dispersion $\sigma_{\mathrm{[Fe/H]}} = 0.38^{+0.07}_{-0.05}$. We calculate the systemic proper motion, orbit, and the astrophysical J-factor for each system, the latter of which indicates that Eri IV is a good target for indirect dark matter detection. We also find no strong evidence for tidal stripping of Cen I or Eri IV. Overall, our measurements confirm that Eri IV and Cen I are dark matter-dominated galaxies with properties largely consistent with other known ultra-faint dwarf galaxies. The low metallicity, right-skewed metallicity distribution, and high J-factor make Eri IV an especially interesting candidate for further followup.Comment: 25 pages, 11 figures, submitted to AAS journal

Mobilizing Crop Biodiversity

Over the past 70 years, the world has witnessed extraordinary growth in crop productivity, 1 enabled by a suite of technological advances, including higher yielding crop varieties, improved farm management, synthetic agrochemicals, and agricultural mechanization. While this “Green Revolution” intensified crop production, and is credited with reducing famine and malnutrition, its benefits were accompanied by several undesirable collateral effects (Pingali, 2012). These include a narrowing of agricultural biodiversity, stemming from increased monoculture and greater reliance on a smaller number of crops and crop varieties for the majority of our calories. This reduction in diversity has created vulnerabilities to pest and disease epidemics, climate variation, and ultimately to human health (Harlan, 1972). The value of crop diversity has long been recognized (Vavilov, 1992). A global system of genebanks (e.g.www.genebanks.org/genebanks/) was established in the 1970s to preserve the abundant genetic variation found in traditional “landrace” varieties of crops and in crop wild relatives (Harlan, 1972). While preserving crop variation is a critical first step, the time has come to make use of this variation to breed more resilient crops. The DivSeek International Network (https://divseekintl.org/) is a scientific, not-for profit organization that aims to accelerate such effort

Human Gastric Mucins Differently Regulate Helicobacter pylori Proliferation, Gene Expression and Interactions with Host Cells

Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA) appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells.

Breast cancer remains one of the leading causes of cancer-associated death worldwide. Conventional treatment is associated with substantial toxicity and suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited 12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist, and an interferon-containing cocktail. The efficacy of the vaccine was evaluated by its ability to elicit a cytotoxic T-lymphocyte response to autologous breast cancer cells in vitro. Matured DCs (≥ 60% upregulation of CD80, CD86, CD83, and CCR7) produced high levels of the Th1 effector cytokine, IL12-p70 (1.2 ng/ml; p < 0.0001), compared to DCs pulsed with tumour lysate, or matured with an interferon-containing cocktail alone. We further showed that matured DCs enhance antigen-specific CD8 + T-cell responses to HER-2 (4.5%; p < 0.005) and MUC-1 (19%; p < 0.05) tetramers. The mature DCs could elicit a robust and dose-dependent antigen-specific cytotoxic T-lymphocyte response (65%) which was tumoricidal to autologous breast cancer cells in vitro compared to T-lymphocytes that were primed with autologous lysate loaded-DCs (p < 0.005). Lastly, we showed that the mature DCs post-cryopreservation maintained high viability, maintained their mature phenotype, and remained free of endotoxins or mycoplasma. We have developed a DC vaccine that is cytotoxic to autologous breast cancer cells in vitro. The tools and technology generated here will now be applied to a phase I/IIa clinical trial

Prevention of Bacterial Endocarditis in Dentistry: the New Guidline

Abstract: The American Heart Association (AHA) has provided new guidelines for infective endocarditis prophylaxis in dentistry. In this paper, written for dentists, major changes in the updated recommendations which dentists should be aware have been discussed. These recommendations address the impact of oral hygiene and type of dental procedures on high-risk patients, risk of adverse reactions of antibiotic therapy, precise administration of antibiotics, underlying cardiac conditions and dental Procedures for which, endocarditis prophylaxis is reasonable for patients. Keywords: Endocarditis, Prevention, Dentistr

Etiology and treatment of oral recurrent aphthous stomatitis

BACKGROUND AND OBJECTIVE: Recurrent Aphthous Stomatitis (RAS) is one of the most common oral mucosal diseases. Nowadays, the majority of published systematic reviews is increasing, hence healthcare decision makers are meeting much evidence in order to solving their clinical problems. The aim of the present umbrella review was to report current knowledge on etiology, diagnosis and treatment of RAS. METHODS: In the present umbrella review, we searched for systematic reviews using PubMed, ISI web of science, Scopus and the Cochrane Library from the beginning of 2000 up to end of 2018 using the following key words: �systematic review� �Meta-analysis� and �aphthous�. Two investigators independently screened, extracted the data, and quality appraised the papers using Joanna Bridges Institute (JBI) protocol. FINDINGS: Finally, 18 systematic reviews were included (8 on etiology and 10 on treatment). Out of these papers, findings of 6 meta-analysis suggested that hematologic deficiencies, interleukin polymorphism and helicobacter pylori seem to have association with RAS, however for treatment of RAS (including: topical, systemic and laser therapy) there were not conclusive findings. CONCLUSION: According to results of this study, hematologic deficiencies, interleukin polymorphism and helicobacter pylori are among the novel etiologies of recurrent aphthous stomatitis, although there is no presented unique and conclusive treatment option for this common lesion yet. © 2020, Babol University of Medical Sciences. All rights reserved