The University of California Center for the Environmental Implications of Nanotechnology.

Assessing nanomaterialsfor human health and ecotoxicological impact can be well aided by using high-throughput laboratory methods.

Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress.

Air Pollution has been associated with significant adverse health effects leading to increased morbidity and mortality. Cumulative epidemiological and experimental data have shown that exposure to air pollutants lead to increased cardiovascular ischemic events and enhanced atherosclerosis. It appears that these associations are much stronger with the air particulate matter (PM) component and that in urban areas, the smaller particles could be more pathogenic, as a result of their greater propensity to induce systemic prooxidant and proinflammatory effects.

Comparative toxicity of C60 aggregates toward mammalian cells: role of tetrahydrofuran (THF) decomposition.

C60 fullerene is a promising material because of its unique physiochemical properties. However, previous studies have reported that colloidal aggregates of C60 (nC60) produce toxicity in fish and human cell cultures. The preparation method of nC60 raises questions as to whether the observed effects stem from fullerenes or from the organic solvents used during the preparation of the suspensions.

Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs.

Surface-functionalized mesoporous silica nanoparticles (MSNP) can be used as an efficient and safe carrier for bioactive molecules. In order to make the MSNP a more efficient delivery system, we modified the surface of the particles by a functional group that enhances cellular uptake and allows nucleic acid delivery in addition to traditional drug delivery. Noncovalent attachment of polyethyleneimine (PEI) polymers to the surface not only increases MSNP cellular uptake but also generates a cationic surface to which DNA and siRNA constructs could be attached.

Oxidative stress and asthma: proteome analysis of chitinase-like proteins and FIZZ1 in lung tissue and bronchoalveolar lavage fluid.

Oxidative stress plays an important role in the development of airway inflammation and hyperreactivity in asthma. The identification of oxidative stress markers in bronchoalveolar lavage fluid (BALF) and lung tissue from ovalbumin (OVA) sensitized mice could provide new insight into disease pathogenesis and possible use of antioxidants to alleviate disease severity. We used two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the impact of the thiol antioxidant, N-acetylcysteine (NAC), on protein expression in a murine OVA model.

Potential health impact of nanoparticles.

Although mankind stands to obtain great benefit from nanotechnology, it is important to consider the potential health impacts of nanomaterials (NMs). This consideration has launched the field of nanotoxicology, which is charged with assessing toxicological potential as well as promoting safe design and use of NMs. Although no human ailments have been ascribed to NMs thus far, early experimental studies indicate that NMs could initiate adverse biological responses that can lead to toxicological outcomes.

The impact of air pollutants as an adjuvant for allergic sensitization and asthma.

The current global epidemic of atopy and asthma has been related to the changes in environmental exposures brought about by the development and expansion of industrialized societies. This article reviews the evidence supporting the fundamental role of air pollutants in fostering allergic inflammation of the airways, with emphasis on the molecular and genetic pathways that link ambient particulate matter (PM) exposure to the induction of proinflammatory changes and proallergic effects in the respiratory tract. We propose that the link between PM exposure and proallergic effects involves organic PM components that generate oxygen radicals capable of perturbing the redox equilibrium mucosal immune cells.

The adjuvant effect of ambient particulate matter is closely reflected by the particulate oxidant potential.

Background: It has been demonstrated that ambient particulate matter (PM) can act as an adjuvant for allergic sensitization. Redox-active organic chemicals on the particle surface play an important role in PM adverse health effects and may determine the adjuvant effect of different particle types according to their potential to perturb redox equilibrium in the immune system.

Objectives: We determined whether the adjuvant effect of ambient fine particles versus ultrafine particles (UFPs) is correlated to their prooxidant potential.

A predictive toxicological paradigm for the safety assessment of nanomaterials.

The rate of expansion of nanomaterials calls for the consideration of appropriate toxicological paradigms in the safety assessment of nanomaterials. We advocate a predictive toxicological paradigm for the assessment of nanomaterial hazards. The predictive toxicological approach is defined as establishing and using mechanisms and pathways of injury at a cellular and molecular level to prioritize screening for adverse biological effects and health outcomes in vivo.

Understanding biophysicochemical interactions at the nano-bio interface.

Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes.

Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways.

The exponential increase in the number of new nanomaterials that are being produced increases the likelihood of adverse biological effects in humans and the environment. In this study we compared the effects of cationic nanoparticles in five different cell lines that represent portal-of-entry or systemic cellular targets for engineered nanoparticles. Although 60 nm NH(2)-labeled polystyrene (PS) nanospheres were highly toxic in macrophage (RAW 264.

Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery.

Drug delivery, magnetic resonance and fluorescence imaging, magnetic manipulation, and cell targeting are simultaneously possible using a multifunctional mesoporous silica nanoparticle. Superparamagnetic iron oxide nanocrystals were encapsulated inside mesostructured silica spheres that were labeled with fluorescent dye molecules and coated with hydrophilic groups to prevent aggregation. Water-insoluble anticancer drugs were delivered into human cancer cells; surface conjugation with cancer-specific targeting agents increased the uptake into cancer cells relative to that in non-cancerous fibroblasts.

Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxide nanoparticles that are currently being produced in high tonnage, TiO(2), ZnO, and CeO(2), were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines.

Innate immune responses during respiratory tract infection with a bacterial pathogen induce allergic airway sensitization.

Background: The original hygiene hypothesis predicts that infections should protect against asthma but does not account for increasing evidence that certain infections might also promote asthma development. A mechanistic reconciliation of these findings has not yet emerged. In particular, the role of innate immunity in this context is unclear.

Mantophasmatodea now in the Jurassic.

The Mantophasmatodea is the most recently discovered insect order. The fossil records of all other 'polyneopteran' orders extend far in the past, but the current absence of pre-Cenozoic fossils of the Mantophasmatodea contradicts a long evolutionary history, which has to be assumed from the morphological distinctness of the group. In this paper, we report the first Mesozoic evidence of a mantophasmatodean from the Middle Jurassic of Daohugou, Inner Mongolia, China.

T-cell effector pathways in allergic diseases: transcriptional mechanisms and therapeutic targets.

Originally interpreted within the framework of a binary T(H)1/T(H)2 paradigm, our knowledge of the pathogenesis of atopic diseases has broadened to incorporate the contribution of T regulatory cells and the newly described proinflammatory T(H)17 cell lineage. The commitment of peripheral T-cell clones to undergo differentiation into one of those lineages is shaped by self-reinforcing transcriptional circuitries that center on key transcriptional regulators: T-box expressed in T cells (T(H)1), GATA-3 (T(H)2), forkhead box p3 (T regulatory cells), and retinoid-related orphan receptor gammatau/retinoid-related orphan receptor alpha (T(H)17). These circuits function both to establish the respective lineage phenotype and to enable epigenetic changes that maintain those phenotypes long-term.

Nrf2 activation by sulforaphane restores the age-related decrease of T(H)1 immunity: role of dendritic cells.

Background: The decrease in cellular immunity with aging is of considerable public health importance. Recent studies suggest that the redox equilibrium of dendritic cells (DCs) is a key factor in maintaining protective cellular immunity and that a disturbance of this homeostatic mechanism could contribute to immune senescence.

Objectives: We sought (1) to elucidate the role of DC redox equilibrium in the decrease of contact hypersensitivity (CHS) and T(H)1 immunity during aging and (2) to determine how restoration of glutathione (GSH) levels by the Nrf2-mediated antioxidant defense pathway affects this decrease.

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles.

Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals.

Phase contrast X-ray synchrotron imaging: opening access to fossil inclusions in opaque amber.

A significant portion of Mesozoic amber is fully opaque. Biological inclusions in such amber are invisible even after polishing, leading to potential bias in paleoecological and phylogenetic studies. Until now, studies using conventional X-ray microtomography focused on translucent or semi-opaque amber.

Evaluating the toxicity of airborne particulate matter and nanoparticles by measuring oxidative stress potential--a workshop report and consensus statement.

Background: There is a strong need for laboratory in vitro test systems for the toxicity of airborne particulate matter and nanoparticles. The measurement of oxidative stress potential offers a promising way forward.

Objectives: A workshop was convened involving leading workers from the field in order to review the available test methods and to generate a Consensus Statement.

Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress.

Air pollution is associated with significant adverse health effects, including increased cardiovascular morbidity and mortality. Exposure to particulate matter with an aerodynamic diameter of <2.5 microm (PM(2.

Importance of oxidative stress in the pathogenesis and treatment of asthma.

Purpose Of Review: The purpose of the current review is to summarize recent evidence demonstrating the important role of oxidative stress in asthma pathogenesis. The therapeutic implications of these findings will be presented.

Recent Findings: Mechanistically, the effect of oxidative stress on dendritic cells has been demonstrated to have a potent effect on Th1/Th2 skewing of the immune response.

The health effects of non-industrial indoor air pollution.

Background: There is growing public awareness regarding the risk associated with poor indoor air quality in the home and workplace. Because Americans spend approximately 22 hours every day indoors, susceptible individuals are at much greater risk of adverse health effects from chronic low levels of exposure to indoor air pollutants over time. Along with particulate matter, gases such as ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide; microbial and chemical volatile organic compounds; passive smoke; and outdoor ambient air are the most common types of air pollutants encountered indoors.

Quesnoin, a novel pentacyclic ent-diterpene from 55 million years Old Oise Amber.

Amber, fossilized tree resin, found at the Oise River area of the Paris basin (France) was dated as being 55 million years old. Quesnoin, a novel unique pure organic compound, was isolated from Oise amber. 1H and 13C NMR spectroscopic analysis indicated an unknown diterpene skeleton, quesnane.