54 research outputs found

    The derepression of transposable elements in lung cells is associated with the inflammatory response and gene activation in idiopathic pulmonary fibrosis

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    Abstract Background Transposable elements (TEs) are repetitive sequences of viral origin that compose almost half of the human genome. These elements are tightly controlled within cells, and if activated, they can cause changes in both gene regulation and immune viral responses that have been associated with several chronic inflammatory diseases in humans. As oxidants are potent activators of TEs, and because oxidative injury is a major risk factor in relation to idiopathic pulmonary fibrosis (IPF), we hypothesized that TEs might be involved in the regulation of gene expression and so contribute to inflammation in cases of IPF. IPF is a fatal lung disease that involves the gradual replacement of the alveolar tissue with fibrotic scars as well as the accumulation of inflammatory cells in the lower respiratory tract. Although IPF is known to occur as a result of the complex interaction between age, environmental risk factors (i.e., oxidative stress) and genetics, the relative contributions of these factors to the disease remain unclear. To determine whether TEs are associated with IPF, we compared the transcriptional profiles of the genes and TEs of lung cells obtained from both healthy donors and IPF patients. Results We quantified TE and gene expression levels using a published bulk RNA-seq dataset containing 24 subjects (16 donors and eight IPF patients), including three lung-cell types per subject, as well as an scRNA-seq dataset concerning 16 subjects (eight donors and eight IPF patients). We found evidence of TE dysregulation in the alveolar type II lung cells and alveolar macrophages of the IPF patients. In addition, the activation of the LINE1 family of elements in IPF is associated with the increased expression of TE cellular regulators (MOV10, IFI16, SAMHD1, and APOBECG3), interferon-stimulating genes (ISG15, IFI6, IFI27, IFI44, and OAS1), chemokines (CX3CL1 and CXCL9), and interleukins (IL15RA). We also propose that TE derepression might be involved in the regulation of previously reported IPF candidate genes (MUC5B, CHL1, SPP1, and MMP7). Conclusion Based on our findings, we propose that TE derepression plays an important role in the regulation of gene expression and can also prompt both the recruitment of inflammatory processes and the disruption of the immunological balance, which can lead to chronic inflammation in IPF

    The effect of SAP and SCM on microstructure development in early age fibre reinforced mortars

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    The use of Supplementary Cementitious Materials (SCMs) in concrete manufacture has significantly increased in the last decades mainly due to their sustainability benefits. Polymeric Fibres (PF) are commonly used in concrete in order to enhance adhesive and frictional bond with a cementitious matrix and improve mechanical properties. Despite these, early age shrinkage of cementitious materials is still a major concern and some form of internal curing is necessary, for example by Superabsorbent polymers (SAP). By providing a continuous supply of water for hydration SAPs influence long term durability and sustainability of mortars. However, the effect of different SAPs on microstructure development in fibre reinforced mortars (FRM) still remains scarce. The current study aims to address this issue. Three commercially available cements: CEM I (PC), CEM II (PC-FA) and CEM III (PC-GGBS) and three types of SAP were analysed. Microstructural features of composites were studied by MIP and SEM techniques. These were accompanied by the elastic modulus analysis of composites. The experimental results showed that application SAP E, with finer particle sizes, results in the lowest total porosities of mortars and greater number of evenly distributed smaller pores (under 20 nm). This subsequently leads to the reduced effect on elastic modulus of FRM. In summary, the smaller SAP particles and more evenly distributed the more efficient in hydration process and more homogenous internal microstructure

    Author Correction: Giant elasto-optic response of gallium selenide on flexible mica

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    Correction to: npj Flexible Electronicshttps://doi.org/10.1038/s41528-024-00375-3, published online 04 January 2025 In the original version of the article in Figs. 2, 3 and 4 and corresponding text, the value of the strain is estimated for different bending radii, r, of the mica, i.e. the strain is calculated as t/2r, where t = 0.03 mm is the thickness of the mica. For example, for r = 4 cm, t/2r = 0.04%. However, as shown in Fig. 1, the mica is bent to a radius of approximately r = 4 mm, not r = 4 cm. Thus, the actual strain is a factor of 10 higher (0.4%) than that reported in the original manuscript and in the original Figs. 2, 3 and 4. The strain is used to calculate and discuss the strain sensitivity of the Raman and photoluminescence spectra (Figs. 2, 3) and its comparison with the modeling from the literature (Fig. 4). The experimental data on the energy shift of the photoluminescence emission versus the applied strain are now more aligned with the modelling, but reveal a variability amongst different samples that is discussed in terms of the exciton thermalization. The strain is used to calculate and discuss the strain sensitivity of the Raman and photoluminescence spectra (Figs. 2, 3) and its comparison with the modeling from the literature (Fig. 4). Thus, it is essential to correct the data to ensure the results are accurately presented. The original article has been corrected

    Targeted Nanostructured Lipid Carriers for Delivery of Paclitaxel to Cancer Cells: Preparation, Characterization, and Cell Toxicity

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    Objective: Low water solubility, high systemic toxicity and insignificant cellular uptake have limited efficient clinical applications of the anti-tumor agent Paclitaxel (PTX). To overcome these limitations, a Novel Nanostructured Lipid Carrier (NLC) modified with Folic Acid (FA) and polyethylene glycol (PEG) was prepared by emulsion solvent evaporation method using cholesterol, alpha-tocopherol, lecithin and Poloxamer. A partial factorial design was applied to determine the appropriate levels of variables for optimized formulation. Formulations were evaluated for Particle Size (PS), Zeta Potential (ZP), Entrapment Efficiency (EE), and release efficiency (RE72). FA- and PEG-conjugated octadecylamine (FA-ODA and PEG-ODA) were synthesized and confirmed by FTIR and H-NMR and incorporated either alone or in combination with the optimized formulation whose properties were also evaluated. PTX-loaded optimized, targeted, pegylated, targeted/pegylated NLCs, pure PTX, and Anzatax (R) along with their respective controls were selected for toxicity evaluation on human breast cancer cell line, MCF-7, using MTT assay. Methods: PS, ZP, EE, and RE72 of the optimized formulation were 154.6 nm, -16.5 mv, 79.1 and 49.3, respectively. Incorporation of alpha-tocopherol as the liquid lipid allowed for more efficient drug encapsulation, PS reduction, enhanced stability and sustained-release of the drug. Cytotoxicity of PTX-loaded NLCs modified with both FA-ODA and PEG-ODA was significantly enhanced compared to that of free PTX and other drug-loaded modified NLCs. Results and Conclusion: The results suggest that preparation of NLCs with synthesized conjugates might be a promising candidate for drug delivery of PTX to the cancerous cells and has a great potential as a carrier for tumor targeting in breast cancer

    Assessment of Manganese-Zinc Ferrite Nanoparticles as a Novel Magnetic Resonance Imaging Contrast Agent for the Detection of 4T1 Breast Cancer Cells

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    Background: The aim of the study was to evaluate the potential of manganese-zinc ferrite nanoparticles (MZF NPs) as a novel negative magnetic resonance imaging (MRI) contrast agents for 4T1 (mouse mammary carcinoma) and L929 (murine fibroblast) cell lines. Methods: MZF NPs and its suitable coating, polyethylene glycol (PEG) via covalent bonding, were investigated under in vitro condition. The cytotoxicity of MZF NPs was tested by 3-(4,5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide assay after 12 and 24 h of incubation. To evaluate the potential of MZF NPs as T2 MRI nanocontrast agent, images were obtained from phantom containing different Fe concentrations and T2 relaxivity (r 2) was measured. The viability of both 4T1 breast cancer and L929 murine fibroblast cell lines incubated with different Fe concentrations. Results: In vitro T2-weighted MRI showed that signal intensity of 4T1 cells was lower than that of L929 as control cells. T2-weighted MRI showed that signal intensity of MZF NPs enhanced with increasing concentration of NPs. The values of 1/T2 relaxivity (r 2) for coated MZF NPs with PEG found to be 85.5 mM(-1) s(-1) which is higher than that of commercially clinical used (Sinerem) MRI contrast agent. Conclusion: The results showed that MZF NPs have potential to detect breast cancer cells (4T1) and also have high contrast resolution between normal (L929) and cancerous cells (4T1) which is a suitable nanoprobe for T2-weighted MR imaging contrast agents

    Beautiful mathematics for beauty-full and other multi-heavy hadronic systems

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    Azizi, Kazem (Dogus Author)In most non-perturbative methods in hadron physics the calculations are started with a correlation function in terms of some interpolating and transition currents in x -space. For simplicity, the calculations are then transformed to the momentum space by a Fourier transformation. To suppress the contributions of the higher states and continuum, and enhance the ground state contribution, the Borel transformation as well as continuum subtraction are applied with the help of quark-hadron duality assumption. In the present study we work out the mathematics required for these processes in the case of light and multi-heavy hadrons. We address a well-known problem in the subtraction of the effects of the higher states and continuum and discuss how we find finite results without any divergence by using an appropriate representation of the modified Bessel functions, appearing in the heavy quark propagator, and successive applications of the Borel transformations, which lead to more suppression of the higher states and continuum contributions. The results obtained can be used in the determination of the spectroscopic and decay properties of the multi-heavy standard and non-conventional (exotic) systems in many non-perturbative methods, especially the QCD sum rules
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