A Toxicology Suite Adapted for Comparing Parallel Toxicity Responses of Model Human Lung Cells to Diesel Exhaust Particles and Their Extracts

Epidemiological studies have shown that exposure to airborne particulate matter (PM) can be an important risk factor for some common respiratory diseases. While many studies have shown that PM exposures are associated with inflammatory reactions, the role of specific cellular responses in the manifestation of primary hypersensitivities and the progression of respiratory diseases remains unclear. In order to better understand mechanisms by which PM can exert adverse health effects, more robust approaches to support in vitro studies are warranted. In response to this need, a group of accepted toxicology assays was adapted to create an analytical suite for screening and evaluating the effects of important, ubiquitous atmospheric pollutants on two model human lung cell lines (epithelial and immature macrophage). To demonstrate the utility of this suite, responses to intact diesel exhaust particles (DEP) and mass-based equivalent doses of their organic extracts were examined. Results suggest that extracts have the potential to induce greater biological responses than those associated with their colloidal counterpart. Additionally, macrophage cells appear to be more susceptible to the cytotoxic effects of both intact DEP and their organic extract, than epithelial cells tested in parallel. As designed, the suite provided a more robust basis for characterizing toxicity mechanisms than the analysis of any individual assay. Findings suggest that cellular responses to PM are cell line dependent, and show that the collection and preparation of PM and/or their extracts have the potential to impact cellular responses relevant to screening fundamental elements of respiratory toxicity.

Copyright 2015 American Association for Aerosol Research     

Polyhydrosilane Mediated Synthesis of One-Dimensional Gold Nanostructures

This work presents a solution-phase approach for the “one pot” synthesis of polysilane-gold nanorods. The process starts by the reduction of HAuCl₄ to Au^o with a solution of poly[diphenylsilane-co-methyl(H)silane] cooled to 4 °C. The formed small Au nanoparticles (5–15 nm diameter) serve further as seeds for the heterogeneous nucleation and anisotropic growth that takes place at 25 °C and yields crystalline needle-like polymer–gold nanostructures. The evolution of the small spherical nanoparticles to nanorods with length/width aspect ratios up to 10³ has been proved by UV–Vis spectroscopy, polarized light microscopy and AFM. Further insights on the growth mechanism were obtained by SEM, DLS and TEM.     

Interfacial chemistry on carboxylate-functionalized monolayer assemblies

Deposition of trichlorosilanes with ester groups at their remote termini provides a convenient entry to carboxylic acid-bearing siloxane-anchored self-assembled monolayers. The de-esterification of these esters has been optimized to minimize monolayer damage, and their quantitative re-esterification provides clear evidence for the stability of these systems. Both the structure of the ester-terminated monolayer and its de-esterification/esterification chemistry can be easily monitored by FTIR-ATR measurements. This spectroscopic tool, together with a liquid cell that enables IR spectra to be measured in an aqueous environment, enables a detailed structural analysis of the carboxylic acid-bearing siloxane-anchored self-assembled monolayers and an assessment of their acid/base behavior (by in situ titration). The use of D₂O instead of H₂O for the in situ titration experiments also improves the available IR window. Both monomeric and dimeric/oligomeric acid groups are seen, and the relative ease of deprotonation of these various species can be directly monitored. Monomers of alkyl carboxylic acids that are hydrogen bonded only to surrounding water molecules have a pK_a = 4.9, while the pK_a for the aggregated molecules is 9.3. Similar behavior is seen for surface-bound benzoic acids, where the two pK_a values are 4.7 and 9.0. The influence of temperature on these structures and their chemistry has been explored to a limited extent as well. When the alkylcarboxylic acid system is cooled to 10 °C, the pK_a value for the acid monomers is reduced from 4.9 to 4.5 and increases from 9.3 to 10.3 for the aggregates.     

Pullulan: A versatile coating agent for superparamagnetic iron oxide nanoparticles

Ultrasmall superparamagnetic iron oxide (Fe₃O₄) nanoparticles coated by biocompatible pullulan (Pu‐USPIO) with sizes below 10 nm and having a magnetite core and a hydrophilic outer shell of pullulan were prepared. The formed Pu‐USPIOs were thoroughly characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, atomic force microscopy, and small‐angle X‐ray scattering experiments. The content of magnetic nanoparticles embedded into the pullulan matrix was determined by thermogravimetric analysis. Vibrating sample magnetometry analysis was used to evaluate the magnetic properties of the Pu‐USPIO samples. Because of the presence of pullulan, these nanoparticles could be conditioned in many versatile forms, from a clear solution to magnetic films, for potential applications, including magnetic hyperthermia mediators. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42926.     

Highly Crosslinked Polysilane–Schiff Base

Summary N,N-Bis(4-hydroxysalicylidene)ethylendiamine (salen) was attached to a poly[iodopropyl(methyl)-co-diphenylsilane)chain. Due to intermolecular crosslinking reactions, a high molecular weight polymer formation was observed. The resulted material was doped with metal cations through complexation reactions. The chemical structure of the polysilane-Schiff base metal complex was investigated by spectral analysis (IR, ¹H-NMR, ¹³C-NMR, UV), thermogravimetric analysis (TGA) and gel permeation chromatography (GPC).     

A Michael-type reaction between acrylato ions and ethylenediamine coordinated to Ni(II). Synthesis,crystal structure and magnetic properties of [Ni2(EDDP)2(H2O)2] · 2H2O (H2EDDP = ethylenediamine-N,N-dipropionic acid)

The reaction between NiCO₃ · Ni(OH)₂, acrylic acid and ethylenediamine in a 2:4:1 molar ratio affords the binuclear complex, [Ni₂(EDDP)₂(H₂O)₂] · 2H₂O 1. The organic ligand, EDDP^2? (the dianion of the ethylenediamine-N,N-dipropionic acid ligand), results from the addition of one amine group to the carbon–carbon double bonds of two acrylato ions. The crystal structure of 1 consists of neutral centrosymmetric entities, with the nickel ions connected by two carboxylato groups, each one acting as a monoatomic bridge. The intramolecular Ni?Ni distance is 3.212 Å. The metal ions exhibit an octahedral geometry. The cryomagnetic investigation of 1 reveals an antiferromagnetic coupling of the nickel(II) ions (J = ?21.8 cm^?1, H = ?JS_Ni1S_Ni2).     

Simultaneous continuous,nonchromatographic monitoring and discrete chromatographic monitoring of polymerization reactions

Automatic continuous nonchromatographic monitoring and discrete chromatographic monitoring were coupled together for the first time and used to monitor free radical and controlled‐radical polymerization reactions. This was achieved by adding a multidetector Size Exclusion Chromatography (SEC) system (alternatively termed Gel Permeation Chromatography, GPC) to the ACOMP platform (Automatic Continuous Online Monitoring of Polymerization reactions). The fact that the reactor solution is already preconditioned in the ACOMP front‐end to the concentration levels used in SEC makes direct coupling possible. Kinetics from two different types of reactions, Reversible Addition Fragmentation Transfer (RAFT) and free radical polymerization of butyl acrylate were studied, including the production of a bimodal population. Complementary and contrasting features from the continuous and SEC approaches are highlighted. The main advantage of the SEC detection is to follow the evolution of full molecular weight distributions (MWD), especially in ‘living’ type reactions, where polydispersity decreases with monomer conversion, whereas the continuous detection provides a much more detailed characterization of the reaction. Interestingly, in the case where a bimodal molecular weight distribution was produced, the continuous method automatically detected the onset of the second mode in a model independent fashion, whereas SEC could only discern the bimodality by applying preconceived models. The SEC approach will have valuable niche applications, however, such as when reactions are relatively slow, monitoring narrow polydispersity is of primary importance, and also in copolymerization and terpolymerization reactions where complex mixtures of reagents (e.g., RAFT agents, copper ions, etc.) make unfractionated spectroscopic resolution of comonomers difficult. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Molecular electronic devices based on single-walled carbon nanotube electrodes

As the top-down fabrication techniques for silicon-based electronic materials have reached the scale of molecular lengths, researchers have been investigating nanostructured materials to build electronics from individual molecules. Researchers have directed extensive experimental and theoretical efforts toward building functional optoelectronic devices using individual organic molecules and fabricating metal-molecule junctions. Although this method has many advantages, its limitations lead to large disagreement between experimental and theoretical results. This Account describes a new method to create molecular electronic devices, covalently bridging a gap in a single-walled carbon nanotube (SWNT) with an electrically functional molecule. First, we introduce a molecular-scale gap into a nanotube by precise oxidative cutting through a lithographic mask. Now functionalized with carboxylic acids, the ends of the cleaved carbon nanotubes are reconnected with conjugated diamines to give robust diamides. The molecular electronic devices prepared in this fashion can withstand and respond to large environmental changes based on the functional groups in the molecules. For example, with oligoanilines as the molecular bridge, the conductance of the device is sensitive to pH. Similarly, using diarylethylenes as the bridge provides devices that can reversibly switch between conjugated and nonconjugated states. The molecular bridge can perform the dual task of carrying electrical current and sensing/recognition through biological events such as protein/substrate binding and DNA hybridization. The devices based on DNA can measure the difference in electrical properties of complementary and mismatched strands. A well-matched duplex DNA 15-mer in the gap exhibits a 300-fold lower resistance than a duplex with a GT or CA mismatch. This system provides an ultrasensitive way to detect single-nucleotide polymorphisms at the individual molecule level. Restriction enzymes can cleave certain cDNA strands assembled between the SWNT electrodes; therefore, these strands maintain their native conformation when bridging the ends of the SWNTs. This methodology for creating novel molecular circuits forges both literal and figurative connections between chemistry, physics, materials science, and biology and promises a new generation of integrated multifunctional sensors and devices.     

GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca²⁺, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.     

Natural Antioxidants in Anemia Treatment

Anemia, characterized by a decrease of the hemoglobin level in the blood and a reduction in carrying capacity of oxygen, is a major public health problem which affects people of all ages. The methods used to treat anemia are blood transfusion and oral administration of iron-based supplements, but these treatments are associated with a number of side effects, such as nausea, vomiting, constipation, and stomach pain, which limit its long-term use. In addition, oral iron supplements are poorly absorbed in the intestinal tract, due to overexpression of hepcidin, a peptide hormone that plays a central role in iron homeostasis. In this review, we conducted an analysis of the literature on biologically active compounds and plant extracts used in the treatment of various types of anemia. The purpose of this review is to provide up-to-date information on the use of these compounds and plant extracts, in order to explore their therapeutic potential. The advantage of using them is that they are available from natural resources and can be used as main, alternative, or adjuvant therapies in many diseases, such as various types of anemia.