Chitosan polysaccharide suppress toll like receptor dependent immune response [Çitosan polisakkaridi toll benzeri reseptöre bağlı bağışıklık yanıtını baskılar]

Objectives: Chitosan is a widely used vaccine or anti-cancer delivery vehicle. In this study, we investigated the immunomodulatory effect of chitosan/pIC nanocomplexes on mouse immune cells. Materials and methods: Proliferative and cytotoxic features of chitosan were tested via CCK-8 assay on RAW 264. 7. IL-1β production was assessed via ELISA from PEC supernatants. TNF-α, and NO induction from chitosan treated RAW cells detected by ELISA and Griess assay, respectively. mRNA message levels of TLRs and cytokines on macrophages in response to chitosan/pIC nanocomplex treatments were evaluated by RT-PCR. Results: Results revealed that chitosan is non-toxic to cells, however, proliferative capacities of macrophages were reduced by chitosan administration. Mouse PECs treated with chitosan, led to NLRP3 dependent inflammasome activation as evidenced by dose-dependent IL-1β secretion. Chitosan/pIC nanocomplexes did not improve immunostimulatory action of pIC on RAW cells, since TNF-α and NO productions remained unaltered. Expression levels of several TLRs, CXCL-16 and IFN-α messages from mouse splenocytes were down regulated in response to chitosan/pIC nanocomplex treatment. Conclusion: Our results revealed that chitosan is an anti-proliferative and inflammasome triggering macromolecule on immune cells. Utilization of chitosan as a carrier system is of concern for immunotherapeutic applications. © 2015 Turkish Journal of Immunology

Involvement of sting-activating cyclic Di-nucleotides on T-cell differentiation and function: An unresolved issue [Sting’i etkinleştiren siklik dinükleotidlerin T hücre diferansiyasyonu ve fonksiyonuna olan etkisi: Çözülmemiş bir sorun]

STING is the pivotal mediator for the recognition of host and pathogenic cytosolic dsDNA as well as cyclic di-nucleotide metabolites from microbes. Studies demonstrated that DNA released from cancerous cells are internalized by innate immune cells such as macrophages and dendritic cells in tumor microenvironment and trigger the production of interferon beta and other pro-inflammatory cytokines including interleukin 6, tumor necrosis factor alpha, and interleukin 12 through STING triggered signaling pathway. Later, these cytokines increase the cytotoxic activity of CD8+ T-cells by increasing the production of interferon gamma. This review discusses the importance of the involvement of STING during the establishment of immunity against intracellular pathogens and its direct effect on T-cells. © 2016 Turkish Journal of Immunology. All rights reserved

Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation.

Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-tetrads. Colocalization of CpG DNA with Toll-like receptor 9 in endosomal vesicles is disrupted by these repetitive elements, although cellular binding and uptake remain unchanged. These findings are the first to establish that specific host-derived molecules can down-regulate the innate immune response elicited by a TLR ligand

Mucinous Cystadenocarcinoma of the Breast with Estrogen Receptor Expression: A Case Report and Review of the Literature

Primary mucinous cystadenocarcinoma (MCA) of the breast was first described by Koenig and Tavassoli in 1998. To our knowledge, only 9 cases of MCA of the breast have been reported. The optimal treatment of MCA could not be defined yet. This article aims to increase the knowledge about this rare variant of breast cancer and to review the literature

Effect of suppressive DNA on CpG-induced immune activation.

Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate a strong innate immune response. This stimulation can be abrogated by either removing the CpG DNA or adding inhibitory/suppressive motifs. Suppression is dominant over stimulation and is specific for CpG-induced immune responses (having no effect on LPS- or Con A-induced activation). Individual cells noncompetitively internalize both stimulatory and suppressive ODN. Studies using ODN composed of both stimulatory and suppressive motifs indicate that sequence recognition proceeds in a 5'-->3' direction, and that a 5' motif can block recognition of immediately 3' sequences. These findings contribute to our understanding of the immunomodulatory activity of DNA-based products and the rules that govern immune recognition of stimulatory and suppressive motifs

Parametrically coupled multiharmonic force imaging

We report use of nonlinear tip-sample interactions to parametrically convert the frequency components of periodic tip-sample interaction forces to frequencies where they can be resonantly detected. One flexural mode of a cantilever is used for tapping-mode imaging and another flexural mode is used for detection of forces converted in presence of an externally injected mechanical oscillation at the difference frequency of the detecting mode and a harmonic of the tapping mode. Material contrast in attractive and repulsive regimes are demonstrated on samples with polymethyl methacrylate patterns and with deoxyribonucleic acid strands on silicon. © 2008 American Institute of Physics

QED blue-sheet effects inside black holes

The interaction of the unboundedly blue-shifted photons of the cosmic microwave background radiation with a physical object falling towards the inner horizon of a Reissner-Nordstrom black hole is analyzed. To evaluate this interaction we consider the QED effects up to the second order in the perturbation expansion. We then extrapolate the QED effects up to a cutoff, which we introduce at the Planckian level. (Our results are not sensitive to the cutoff energy.) We find that the energy absorbed by an infalling observer is finite, and for typical parameters would not lead to a catastrophic heating. However, this interaction would almost certainly be fatal for a human being, or other living organism of similar size. On the other hand, we find that smaller objects may survive the interaction. Our results do not provide support to the idea that the Cauchy horizon is to be regarded as the boundary of spacetime.Comment: 6 pages, LaTeX. To appear in Phys. Rev.

Impact of pre‐analytical sample handling factors on plasma biomarkers of Alzheimer's disease

An unmet need exists for reliable plasma biomarkers of amyloid pathology, in the clinical laboratory setting, to streamline diagnosis of Alzheimer's disease (AD). For routine clinical use, a biomarker must provide robust and reliable results under pre-analytical sample handling conditions. We investigated the impact of different pre-analytical sample handling procedures on the levels of seven plasma biomarkers in development for potential routine use in AD. Using (1) fresh (never frozen) and (2) previously frozen plasma, we evaluated the effects of (A) storage time and temperature, (B) freeze/thaw (F/T) cycles, (C) anticoagulants, (D) tube transfer, and (E) plastic tube types. Blood samples were prospectively collected from patients with cognitive impairment undergoing investigation in a memory clinic. β-amyloid 1-40 (Aβ40), β-amyloid 1-42 (Aβ42), apolipoprotein E4, glial fibrillary acidic protein, neurofilament light chain, phosphorylated-tau (phospho-tau) 181, and phospho-tau-217 were measured using Elecsys® plasma prototype immunoassays. Recovery signals for each plasma biomarker and sample handling parameter were calculated. For all plasma biomarkers measured, pre-analytical effects were comparable between fresh (never frozen) and previously frozen samples. All plasma biomarkers tested were stable for ≤24 h at 4°C when stored as whole blood and ethylenediaminetetraacetic acid (EDTA) plasma. Recovery signals were acceptable for up to five tube transfers, or two F/T cycles, and in both polypropylene and low-density polyethylene tubes. For all plasma biomarkers except Aβ42 and Aβ40, analyte levels were largely comparable between EDTA, lithium heparin, and sodium citrate tubes. Aβ42 and Aβ40 were most sensitive to pre-analytical handling, and the effects could only be partially compensated by the Aβ42/Aβ40 ratio. We provide recommendations for an optimal sample handling protocol for analysis of plasma biomarkers for amyloid pathology AD, to improve the reproducibility of future studies on plasma biomarkers assays and for potential use in routine clinical practice

Metrics for minimising environmental impacts while maximising circularity in biobased products: The case of lignin-based asphalt

Achieving a circular economy (CE) is seen by society and policymakers as crucial to achieving a sustainable, resource-efficient, renewable and competitive economy. Given the current threat of climate change, we must develop new products that not only maximise the circularity of resources but also minimise climate change impacts. While these two goals are usually aligned, trade-offs exist. For instance, recycling biobased asphalt is a better end-of-life option than landfilling from a resource efficiency perspective. However, landfilling of biogenic non-biodegradable material leads to permanent carbon storage and, therefore, climate benefits. To fully understand the potential benefits and impacts of biobased circular innovations, we need metrics to capture their complexity from both a circular and climate point of view. This study explores the use of different circularity and sustainability metrics to understand the impacts and trade-offs of lignin-based versus bitumen-based asphalts. The analysis is done by calculating the Material Circularity Index (MCI) and two newly developed indicators quantifying the biogenic carbon storage (BCS) of products (BCS100 and c-BCS) while following the CE principles. In addition, the impacts regarding climate change, life cycle costs and ECI (environmental costs indicator) are also provided. Based on the MCI, it can be concluded that lignin-based asphalt roads have slightly higher material circularity than their bitumen-based counterparts. The BCS analysis indicated that the least circular lignin-based alternative sequesters the highest amount of carbon in the long term due to permanent storage in foundations. Despite these trade-offs, the results from the newly developed BCS indicators allowed to align both climate and circularity goals, guiding policymakers and industry actors to implement circular biobased strategies where the value of biobased materials is optimised. Finally, this article discusses the use of different circularity and environmental metrics for decision making in the context of a circular biobased economy