23 research outputs found
The derepression of transposable elements in lung cells is associated with the inflammatory response and gene activation in idiopathic pulmonary fibrosis
No full textAbstract 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
Aggregate and Microcarrier Cultures of Human Pluripotent Stem Cells in Stirred-Suspension Systems
No full textTargeted Nanostructured Lipid Carriers for Delivery of Paclitaxel to Cancer Cells: Preparation, Characterization, and Cell Toxicity
No full textObjective: 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
No full textBackground: 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
[C<sub>6</sub>(MIm)<sub>2</sub>]<sub>2</sub>W<sub>10</sub>O<sub>32</sub>. 2H<sub>2</sub>O: A novel and powerful catalyst for the synthesis of 4-arylidene-2-phenyl-5(4)-oxazolones under ultrasonic condition
No full textChemInform Abstract: An Efficient, Simple, and Scaleable Domino Reaction to Diverse N-(1-Oxo-1H-inden-2-yl)benzamides Catalyzed by HPW@nano-SiO2 under Microwave Irradiation.
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A simple conversion of azlactones into indenones via H3PW12O40/Al2O3 catalyzed intramolecular Friedel–Crafts reaction
No full text[C6(MIm)2]2W10O32. 2H2O: A novel and powerful catalyst for the synthesis of 4-arylidene-2-phenyl-5(4)-oxazolones under ultrasonic condition
No full textSingle-Cell Transcriptome Analysis of Mouse Liver Cell-Specific Tropism and Transcriptional Dysregulation Following Intravenous Administration of AAVrh.10 Vectors
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