Marine Bile Natural Products as Agonists of the TGR5 Receptor.

Agonism of the G protein-coupled bile acid receptor "Takeda G-protein receptor 5" (TGR5) aids in attenuating cholesterol accumulation due to atherosclerotic progression. Although mammalian bile compounds can activate TGR5, they are generally weak agonists, and more effective compounds need to be identified. In this study, two marine bile compounds (5β-scymnol and its sulfate) were compared with mammalian bile compounds deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) using an model of TGR5 agonism.

An advanced method for quantitative measurements of cholesterol crystallization.

Background: Cholesterol crystallization within an atherosclerotic plaque significantly contributes to the acceleration of plaque rupture - a problematic event due to the current lack of specific treatments to prevent such formations. Modelling this pathogenic process is also difficult due to the lack of suitable experimental models that enable quantitative analysis of crystal formation and bioactivity screening of potential therapeutic compounds.

Aim: To develop an in vitro human cell model of cholesterol crystallization combined with an imaging system that incorporates both quantitative analysis and real-time continuous imaging of cholesterol crystal formation.

Samarium doped titanium dioxide nanoparticles as theranostic agents in radiation therapy.

Purpose: Titanium dioxide nanoparticles (TiO NPs) have been investigated for their role as radiosensitisers for radiation therapy. The study aims to increase the efficiency of these NPs by synthesising them with samarium.

Methods: Samarium-doped TiO NPs (Ti(Sm)O NPs) were synthesised using a solvothermal method.

Combined Effects of Gold Nanoparticles and Ionizing Radiation on Human Prostate and Lung Cancer Cell Migration.

The effect of 15 nm-sized gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the migration and adhesion of human prostate (DU145) and lung (A549) cancer cell lines was investigated. Cell migration was measured by observing the closing of a gap created by a pipette tip on cell monolayers grown in 6-well plates. The ratio of the gap areas at 0 h and 24 h were used to calculate the relative migration.

ZnO nanoparticles and organic chemical UV-filters are equally well tolerated by human immune cells.

An important part of assessing the toxic potential of nanoparticles for specific applications should be the direct comparison of biological activities with those of alternative materials for the same application. Nanoparticulate inorganic ultraviolet (UV) filters, such as zinc oxide (ZnO), are commonly incorporated into transparent sunscreen and cosmetic formulations. However, concerns have been raised about potential unwanted effects, despite their negligible skin penetration and inherent advantages over organic chemical UV-filters.

Investigating the immunomodulatory nature of zinc oxide nanoparticles at sub-cytotoxic levels in vitro and after intranasal instillation in vivo.

Background: This study evaluates the time-dependent pro-inflammatory response of the model human lung epithelial cells (A549) to industrially relevant zinc oxide nanoparticles (ZnO NPs). In terms of toxicity, ZnO-NPs are categorised into the group of high toxicity nanomaterials. However information on pro-inflammatory potential of these NPs at sub-toxic concentrations is limited.

Reducing ZnO nanoparticle cytotoxicity by surface modification.

Nanoparticulate zinc oxide (ZnO) is one of the most widely used engineered nanomaterials and its toxicology has gained considerable recent attention. A key aspect for controlling biological interactions at the nanoscale is understanding the relevant nanoparticle surface chemistry. In this study, we have determined the disposition of ZnO nanoparticles within human immune cells by measurement of total Zn, as well as the proportions of extra- and intracellular dissolved Zn as a function of dose and surface coating.

Comparison of UVA-induced ROS and sunscreen nanoparticle-generated ROS in human immune cells.

Oxidative damage to cells and tissues from free radicals induced by ultraviolet (UV) irradiation can be attenuated by sunscreen components, such as ZnO and TiO2 nanoparticles (NPs). Although it is known that reactive oxygen species (ROS) are generated by cells upon exposure to ZnO and TiO2 NPs, it is unknown to what extent the amount generated is altered with UV co-exposure. As it is a critical component for determining the relative risk of these NPs when used in sunscreen formulations, we have investigated ROS generation by these NPs in human THP-1 monocyte immune cells following UVA co-exposure.

Quantification of ZnO nanoparticle uptake, distribution, and dissolution within individual human macrophages.

The usefulness of zinc oxide (ZnO) nanoparticles has led to their wide distribution in consumer products, despite only a limited understanding of how this nanomaterial behaves within biological systems. From a nanotoxicological viewpoint the interaction(s) of ZnO nanoparticles with cells of the immune system is of specific interest, as these nanostructures are readily phagocytosed. In this study, rapid scanning X-ray fluorescence microscopy was used to assay the number ZnO nanoparticles associated with ∼1000 individual THP-1 monocyte-derived human macrophages.

Relating cytotoxicity, zinc ions, and reactive oxygen in ZnO nanoparticle-exposed human immune cells.

Although zinc oxide (ZnO) nanoparticles (NPs) have been widely formulated in sunscreens, the relationship between reactive oxygen species (ROS) generation induced by these particles, zinc ions, and cytotoxicity is not clearly understood. This study explores whether these factors can be accurately quantified and related. The study demonstrates a strong correlation between ZnO NP-induced cytotoxicity and free intracellular zinc concentration (R (2) = .

Formation of zinc-containing nanoparticles from Zn²⁺ ions in cell culture media: implications for the nanotoxicology of ZnO.

Zinc ions generate a range of poorly soluble Zn-containing nanoparticles when added to commonly used mammalian cell culture media. The formation of these nanoparticles confounds the use of soluble Zn salts as positive controls during cytotoxicity testing of other Zn-containing nanoparticles, such as ZnO. These nanoprecipitates can either be crystalline or amorphous and vary in composition depending upon the concentration of Zn(II) within the medium.

Independent cytotoxic and inflammatory responses to zinc oxide nanoparticles in human monocytes and macrophages.

Significant public and scientific concerns remain for the use of nanoparticles (NPs) in commercial products, particularly those applied topically for skin care. There are currently a range of metal oxides formulated into many sunscreens that are present at the nanoscale. In this study, we sought to determine the effect of the size and dispersion of one type of these NPs (zinc oxide) on immune cell function and cytotoxicity for human macrophages and monocytes, which are key cells for particle and debris clearance in the skin.

Increased vascular endothelial growth factor and receptors: relationship to angiogenesis in asthma.

Rationale: Increased vascularity is a feature of airway remodeling in asthma with the potential to contribute to a number of functional abnormalities in this chronic disease. Although various growth factors have been implicated in modulating vascularity, the important contributors in vivo are still being elucidated. The most likely candidate is vascular endothelial growth factor (VEGF).

BAL eotaxin and IL-5 in asthma, and the effects of inhaled corticosteroid and beta2 agonist.

Objective: In a longitudinal ex vivo placebo-controlled study, asthmatics already treated with inhaled corticosteroid received supplemental long-acting beta-agonist (LABA) or increased doses of their inhaled corticosteroid (ICS). Previously reports have shown significant reductions in biopsy eosinophil numbers after treatment with LABA. Following these findings, eosinophil chemokines eotaxin and IL-5 in the BAL fluid at baseline and after 3 months of study medication have now been measured, and these data with that from new cross-sectional controls have also been compared.