The discovery of regional neurotoxicity-associated metabolic alterations induced by carbon quantum dots in brain of mice using a spatial metabolomics analysis.

BACKGROUND: Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development. RESULTS: In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson's disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures. CONCLUSION: These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.

Nitrogen-doped graphene quantum dots induce ferroptosis through disrupting calcium homeostasis in microglia.

BACKGROUND: Along with the wild applications of nitrogen-doped graphene quantum dots (N-GQDs) in the fields of biomedicine and neuroscience, their increasing exposure to the public and potential biosafety problem has gained more and more attention. Unfortunately, the understanding of adverse effects of N-GQDs in the central nervous system (CNS), considered as an important target of nanomaterials, is still limited. RESULTS: After we found that N-GQDs caused cell death, neuroinflammation and microglial activation in the hippocampus of mice through the ferroptosis pathway, microglia was used to assess the molecular mechanisms of N-GQDs inducing ferroptosis because it could be the primary target damaged by N-GQDs in the CNS. The microarray data suggested the participation of calcium signaling pathway in the ferroptosis induced by N-GQDs. In microglial BV2 cells, when the calcium content above the homeostatic level caused by N-GQDs was reversed, the number of cell death, ferroptosis alternations and excessive inflammatory cytokines release were all alleviated. Two calcium channels of L-type voltage-gated calcium channels (L-VGCCs) in plasma membrane and ryanodine receptor (RyR) in endoplasmic reticulum (ER) took part in N-GQDs inducing cytosolic calcium overload. L-VGCCs and RyR calcium channels were also involved in promoting the excess iron influx and triggering ER stress response, respectively, which both exert excessive ROS generation and result in the ferroptosis and inflammation in BV2 cells. CONCLUSION: N-GQDs exposure caused ferroptosis and inflammatory responses in hippocampus of mice and cultured microglia through activating two calcium channels to disrupt intracellular calcium homeostasis. The findings not only posted an alert for biomedical applications of N-GQDs, but also highlighted an insight into mechanism researches of GQDs inducing multiple types of cell death in brain tumor therapy in the future.

NADPH oxidases regulate endothelial inflammatory injury induced by PM2.5 via AKT/eNOS/NO axis.

Fine particulate matter (PM2.5 )-induced detrimental cardiovascular effects have been widely concerned, especially for endothelial cells, which is the first barrier of the cardiovascular system. Among potential mechanisms involved, reactive oxidative species take up a crucial part. However, source of oxidative stress and its relationship with inflammatory response have been rarely studied in PM2.5 -induced endothelial injury. Here, as a key oxidase that catalyzes redox reactions, NADPH oxidase (NOX) was investigated. Human umbilical vein endothelial cells (EA.hy926) were exposed to Standard Reference Material 1648a of urban PM2.5 for 24 h, which resulted in NOX-sourced oxidative stress, endothelial dysfunction, and inflammation induction. These are manifested by the up-regulation of NOX, increase of superoxide anion and hydrogen peroxide, elevated endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) level, reduced nitric oxide (NO) production, and down-regulation of phosphorylation of endothelial NO synthase (eNOS) with increased levels of inducible NO synthase, as well as the imbalance between tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1), and changes in the levels of pro-inflammatory and anti-inflammatory factors. However, administration of NOX1/4 inhibitor GKT137831 alleviated PM2.5 -induced elevated endothelial dysfunction biomarkers (NO, ET-1, ADMA, iNOS, and tPA/PAI-1), inflammatory factors (IL-1ß, IL-10, and IL-18), and adhesion molecules (ICAM-1, VCAM-1, and P-selectin) and also passivated NOX-dependent AKT and eNOS phosphorylation that involved in endothelial activation. In summary, PM2.5 -induced NOX up-regulation is the source of ROS in EA.hy926, which activated AKT/eNOS/NO signal response leading to endothelial dysfunction and inflammatory damage in EA.hy926 cells.

Ag2Se quantum dots damage the nervous system of nematode Caenorhabditis elegans.

Silver selenide quantum dots (Ag2Se QDs), as a novel type of QDs, are valuable in the biomedical application due to their low-toxic and excellent optical property in near infrared region, but the biosafety assessment of Ag2Se QDs is rare. In this study, the findings suggested that the accumulation of Ag2Se QDs in the body of nematodes decreased the lifespan and damaged normal neurobehaviors of Caenorhabditis elegan (C. elegans). Furthermore, Ag2Se QDs caused excessive reactive oxygen species (ROS) productions and altered expressions of several genes associated with redox equilibrium, which might contribute to neurotoxic outcomes in nematode C. elegans. According to this study, it is necessary and important for researchers to pay attention to the biosafety assessment of presumed low-toxic nanomaterials, like Ag2Se QDs, especially on sensitively toxic targets, i.e. the nervous system.

Neurobehavior and neuron damage following prolonged exposure of silver nanoparticles with/without polyvinylpyrrolidone coating in Caenorhabditis elegans.

Silver nanoparticles (AgNPs) have become widespread in the environment with increasing industrial applications. But the studies about their potential health risks are far from enough, especially in neurotoxic effects. This study aimed to investigate the neurotoxic effects of longer-term exposure (prolonged exposure for 48 h and chronic exposure for 6 days) of 20nm AgNPs with/without polyvinylpyrrolidone (PVP) coating at low concentrations (0.01-10 mg·L-1 ) to Caenorhabditis elegans. The results suggested that exposure to AgNPs induced damage to nematode survival, with the longest and relative average life span reduced. Exposure to AgNPs caused neurotoxicity on locomotion behaviors (head thrashes, body bends, pharyngeal pumping frequency, and defecation interval) and sensory perception behaviors (chemotaxis assay and thermotaxis assay), as well as impaired dopaminergic, GABAergic, and cholinergic neurons, except for glutamatergic, based on the alters fluorescence intensity, in a dose- and time-dependent manner. Further investigations suggested that the low-dose AgNPs (0.01-0.1 mg·L-1 ) exposure raises receptors of GABAergic and dopamine in C. elegans at the genetic level, whereas opposite results were observed at higher doses (1-10 mg·L-1 ), which implied that AgNPs could cause neurotoxicity by impairing neurotransmitter delivery. The PVP-AgNPs could cause a higher fatality rate and neurotoxicity at the same dose. Notably, AgNPs did not cause any deleterious effect on nematodes at the lowest dose of 0.01 mg·L-1 . In general, these results suggested that AgNPs possess the neurotoxic potential in C. elegans and provided useful information to understand the neurotoxicity of AgNPs, which would offer an inspiring perspective on the safe application.

Identification of potential circRNA-miRNA-mRNA regulatory networks in response to graphene quantum dots in microglia by microarray analysis.

Along with the increasing application of graphene quantum dots (GQDs) in the fields of biomedicine and neuroscience, it is important to assess the probably adverse effects of GQDs in the central nervous system (CNS) but their underlying toxic mechanisms is still unclear. In this study, we evaluate the molecular mechanisms associated with circular RNAs (circRNAs) of nitrogen-doped GQDs (N-GQDs) and amino-functionalized GQDs (A-GQDs) damaging the cell viability and cellular structure in microglia by an integrative analysis of RNA microarray. The differentially expressed circRNA (DEcircRNAs)-miRNA- differentially expressed mRNA (DEmRNAs) regulatory networks were conducted in BV2 microglial cells treated with 25 µg/mL N-GQDs, 100 µg/mL N-GQDs and 100 µg/mL A-GQDs. Based on that, the protein-coding genes in each ceRNA network were collected to do bio-functional analysis to evaluate signaling pathways that were indirectly mediated by circRNAs. Some pathways that could play indispensable roles in the neurotoxicity of N-GQDs or both two kinds of GQDs were found. Low-dosed N-GQDs exposure mainly induced inflammatory action in microglia, while high-dosed N-GQDs and A-GQDs exposure both affect olfactory transduction and GABAergic synapse. Meanwhile, several classical signaling pathways, including mTOR, ErbB and MAPK, could make diverse contributions to the neurotoxicity of both two kinds of GQDs. These circRNAs could be toxic biomarkers or protective targets in neurotoxicity of GQDs. More importantly, they emphasized the necessity of comprehensive analysis of latent molecular mechanisms through epigenetics approaches in biosafety assessment of graphene-based nanomaterials.

Mitophagy-lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells.

With the increasing use of silver nanoparticles (AgNPs) in biological materials, the cytotoxicity caused by these particles has attracted much attention. However, the molecular mechanism underlying AgNP cytotoxicity remains unclear. In this study, we aimed to systematically investigate the toxicity induced by AgNP exposure to the lung adenocarcinoma A549 cell line at the subcellular and signaling pathway levels and elucidate the related molecular mechanism. The survival rate of cells exposed to AgNPs at 0, 20, 40, 80, and 160 µg/mL for 24 or 48 h decreased in a dose- and time-dependent manner. AgNPs induced autophagy and mitophagy, determined by the transmission electron microscopy investigation and upregulation of LC3 II/I, p62, PINK1, and Parkin expression levels. AgNP treatment induced lysosomal injury, including the decline of lysosomal membrane integrity and increase in cathepsin B level. The decreased in mitochondrial membrane potential, along with upregulation of cytochrome c, caspases 9 and 3, and BAX/BCL2, further suggested that mitochondrial injury were involved in AgNP-induced apoptosis. In addition, mitochondrial injury may further lead to excessive production of reactive oxygen species and oxidative/ antioxidant imbalance. The results suggested that AgNPs could regulate autophagy via mitochondrial and lysosome injury in A549 cells. The information of the molecular mechanism will provide an experimental basis for the safe application of nanomaterials.

Mesoporous Silica Nanoparticles at Predicted Environmentally Relevant Concentrations Cause Impairments in GABAergic Motor Neurons of Nematode Caenorhabditis elegans.

Available safety evaluations regarding mesoporous silica nanoparticles (mSiNPs) are based on the assumption of a relatively high exposure concentration, which makes the findings less valuable in a realistic environment. In this study, we employed Caenorhabditis elegans (C. elegans) as a model to assess the neuronal damage caused by mSiNPs at the predicted environmentally relevant concentrations. After nematodes were acute and prolonged exposed to mSiNPs at concentrations over 300 µg/L, locomotion degeneration, shrinking behavior, and abnormal foraging behavior were observed, which were associated with the deficits in the development of GABAergic neurons, including D-type and RME motor neurons. Furthermore, the oxidative stress evidenced by excessive ROS generation might contribute to the mechanism of mSiNPs damaging neurons. Although the neurotoxicity of mSiNPs was weaker than (nonmesoporous) SiNPs, it is still necessary for researchers to pay attention to the adverse effects caused by mSiNPs in the environmental animals, especially with the rapid increase in mSiNPs application. Considering the conserved property of GABAergic neurons during evolution, these findings will shed light on our understanding of the potential eco-risks of NPs to the nervous system of other animal models.

Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia.

BACKGROUND: Graphene quantum dots (GQDs) provide a bright prospect in the biomedical application because they contain low-toxic compounds and promise imaging of deep tissues and tiny vascular structures. However, the biosafety of this novel QDs has not been thoroughly evaluated, especially in the central nervous system (CNS). The microarray analysis provides a hint that nitrogen-doped GQDs (N-GQDs) exposure could cause ferroptosis in microglia, which is a novel form of cell death dependent on iron overload and lipid peroxidation. RESULTS: The cytosolic iron overload, glutathione (GSH) depletion, excessive reactive oxygen species (ROS) production and lipid peroxidation (LPO) were observed in microglial BV2 cells treated with N-GQDs, which indicated that N-GQDs could damage the iron metabolism and redox balance in microglia. The pre-treatments of a specific ferroptosis inhibitor Ferrostatin-1 (Fer-1) and an iron chelater Deferoxamine mesylate (DFO) not only inhibited cell death, but also alleviated iron overload, LPO and alternations in ferroptosis biomarkers in microglia, which were caused by N-GQDs. When assessing the potential mechanisms of N-GQDs causing ferroptosis in microglia, we found that the iron content, ROS generation and LPO level in mitochondria of BV2 cells all enhanced after N-GQDs exposure. When the antioxidant ability of mitochondria was increased by the pre-treatment of a mitochondria targeted ROS scavenger MitoTEMPO, the ferroptotic biological changes were effectively reversed in BV2 cells treated with N-GQDs, which indicated that the N-GQDs-induced ferroptosis in microglia could be attributed to the mitochondrial oxidative stress. Additionally, amino functionalized GQDs (A-GQDs) elicited milder redox imbalance in mitochondria and resulted in less ferroptotic effects than N-GQDs in microglia, which suggested a slight protection of amino group functionalization in GQDs causing ferroptosis. CONCLUSION: N-GQDs exposure caused ferroptosis in microglia via inducing mitochondrial oxidative stress, and the ferroptotic effects induced by A-GQDs were milder than N-GQDs when the exposure method is same. This study will not only provide new insights in the GQDs-induced cell damage performed in multiple types of cell death, but also in the influence of chemical modification on the toxicity of GQDs.

The glycolytic shift was involved in CdTe/ZnS quantum dots inducing microglial activation mediated through the mTOR signaling pathway.

The excellent optical property and relatively low toxicity of CdTe/ZnS core/shell quantum dots (QDs) make them an advanced fluorescent probe in the application of biomedicines, particularly in neuroscience. Thus, it is important to evaluate the biosafety of CdTe/ZnS QDs on the central nervous system (CNS). Our previous studies have suggested that the high possibility of CdTe/ZnS QDs being transported into the brain across the blood-brain barrier resulted in microglial activation and a shift of glycometabolism, but their underlying mechanism remains unclear. In this study, when mice were injected intravenously with CdTe/ZnS QDs through tail veins, the microglial activation, polarized into both M1 phenotype and M2 phenotype, and the neuronal impairment were observed in the hippocampus. Meanwhile, the increased pro- and anti-inflammatory cytokines released from BV2 microglial cells treated with CdTe/ZnS QDs also indicated that QD exposure was capable of inducing microglial activation in vitro. We further demonstrated that the glycolytic shift from oxidative phosphorylation switching into aerobic glycolysis was required in the microglial activation into M1 phenotype induced by CdTe/ZnS QD treatment, which was mediated through the mTOR signaling pathway. The findings, taken together, provide a mechanistic insight regarding the CdTe/ZnS QDs inducing microglial activation and the role of the glycolytic shift in it.

Biodistribution and organ oxidative damage following 28 days oral administration of nanosilver with/without coating in mice.

This study evaluated the biodistribution and organ oxidative effects of silver nanoparticles (AgNPs) coated with/without polyvinylpyrrolidone (PVP) (AgNP-20 and AgNP-PVP) in mice; these were administered by gavage at a dose of 10-250 mg/kg body weight per day for 28 days. The results showed that both the AgNPs could induce subacute toxicity and oxidative damage to mice and were mainly accumulated in the liver and spleen and excreted by feces. AgNPs could be absorbed into blood and might cross the blood-brain barrier, and be distributed extensively in mice. The malondialdehyde content in the liver, lungs and kidneys increased in both AgNP groups, while the content of glutathione decreased, and the activity of superoxide dismutase increased at first and then decreased along with the increased doses. Inflammatory pathological changes in the lung and liver at high dose of both AgNPs were consistent with increases in glutamate pyruvic transaminase, glutamate oxaloacetic transaminase and the total protein in serum detection. The Ag content was detected in organs, with the highest content in the liver, followed by spleen, while the Ag content in feces was about 500 times higher than that in urine. AgNP-PVP could induce higher oxidative stress and subacute toxicity than AgNP-20 at the same dose, which might be related to the higher concentrations and more Ag+ ions released in mice after AgNP-PVP exposure. The data from this research provided information on toxicity and biodistribution of AgNPs following gavage administration in mice, and might shed light for future application of AgNPs in daily life.

Genotoxic effects of silver nanoparticles with/without coating in human liver HepG2 cells and in mice.

With the rapid expansion of human exposure to silver nanoparticles (AgNPs), the genotoxicity screening is critical to the biosafety evaluation of nanosilver. This study assessed DNA damage and chromosomal aberration in the human hepatoma cell line (HepG2) as well as the effects on the micronucleus of bone marrow in mice induced by 20 nm polyvinylpyrrolidone-coated nanosilver (PVP-AgNPs) and 20 nm bare nanosilver (AgNPs). Our results showed that the two types of AgNPs, in doses of 20-160 µg/mL, could cause genetic toxicological changes on HepG2 cells. The DNA damage degree of HepG2 cells in 20 nm AgNPs was higher than that in 20 nm PVP-AgNPs, while the 20 nm PVP-AgNPs caused more serious chromosomal aberration than 20 nm AgNPs. Both kinds of AgNPs caused genetic toxicity in a dose-dependent manner in HepG2 cells. In the micronucleus test on mouse bone marrow cells, in doses of 10, 50 and 250 mg/kg body weight administered orally for 28 days once a day, the two kinds of AgNPs have no obvious inhibitory effect on the mouse bone marrow cells, and the effect of chromosome aberration could be documented at the high dose of 250 mg/kg. These results suggest that AgNPs have genotoxic effects in HepG2 cells and limited effects on bone marrow in mice; both in vitro and in vivo tests could be of great importance on the evaluation of genotoxicity of nanosilver. These findings can provide useful toxicological information that can help to assess genetic toxicity of nanosilver in vitro and in vivo.

DNA damage in BV-2 cells: An important supplement to the neurotoxicity of CdTe quantum dots.

Microglial cells are resident immune cells in the central nervous system. Activation of microglia as induced by CdTe quantum dots (QDs) can trigger damage to neurons. To quantify the intracellular QDs, we monitored the intracellular Cd concentration in the QD-exposed mouse microglial cells (BV-2 cell line). The extent of cell injury at different times correlated with the Cd concentration in cells at that time. In addition to Cd ion detection, we also monitored the intracellular fluorescence of the QDs. More QDs accumulated in the nucleus than in the cytoplasm. Comet assays confirmed that QDs induce DNA damage. However, DNA cannot interact with QDs, so the DNA damage was not caused by CdTe QDs adducts to DNA but by the increase of the Cd ion concentration and the secondary oxidative damage. In addition to DNA damage, biofilm injury and endogenous reduced glutathione depletion were also apparent in QD-exposed BV-2 cells. These changes can be prevented or even reversed by exogenous reduced glutathione administration.

Identification of mRNA-miRNA crosstalk in human endothelial cells after exposure of PM2.5 through integrative transcriptome analysis.

PM2.5 has implications in cardiovascular adverse events, but the underlying mechanisms are still obscure. The aim of this study is to evaluate miRNA expression in endothelial cells in response to two realistic doses of PM2.5 and to identify the possible gene targets of deregulated miRNAs through microarray profiling and computational technology. As a result, there are 18 differentially expressed miRNAs between 2.5 µg/cm2 group and the control, of which 11 miRNAs are up-regulated and 7 miRNAs are down-regulated. Relative to the control group, 40 miRNAs are significantly changed in 10 µg/cm2 group with 21 miRNAs being upregulated and 19 miRNAs being downregulated. Interestingly, when two PM2.5-treated groups respectively compared with the control, the expressed trends of 12 miRNAs in 2.5 µg/cm2 group are the same as those in 10 µg/cm2 group, with 8 being upregulated and 4 miRNAs being simultaneously downregulated. Gene ontology (GO) analysis shows that the crucial functional categories of miRNA-targeted genes incorporate transcription-related process and intracellular signal transduction. Pathway analysis reveals that endocytosis, FoxO signaling pathway and PI3K-Akt signaling pathway are involved in the PM2.5-caused cardiotoxicity. Further confirmation by RT-qPCR indicates that PM2.5 could induce the down-regulation of hsa-miR-128-3p, hsa-miR-96-5p, hsa-miR-28-5p, hsa-miR-4478 and hsa-miR-6808-5p, which are in accordance with the results of array data. With the comprehensive analysis of mRNAs and miRNAs, a great number of pairs have been identified, suggesting abnormally expressed miRNAs have functions in the cardiotoxicity of PM2.5, and the function may be achieved through the post-transcriptional regulation of certain genes on the related pathways.

Review of the effects of manufactured nanoparticles on mammalian target organs.

Nanotechnology had matured significantly during the last two decades as it has transitioned from bench top science to applied technology. Even though the issue of safety of nanotechnology has been raised nearly one decade ago, the rapid progress in development and use of nanomaterials has not yet been matched by toxicological investigations. Many recent studies have simply outlined the toxic effects of nanoparticles (NPs), but few have systematically addressed their potentially adverse biological effects on target organs. Some animal models have shown that NPs could be accumulated in various organs. These accumulations can access the vasculature and target other organs, resulting in a potential health risks. After the brief description of current knowledge on the wide applications of several common NPs, their applications and the toxicokinetics, this review focused on effects of NPs on organ functions and mammal health after acute or chronic exposure, and potential mechanisms of action. Due to their physical properties, the liver, kidneys and lung are the main target organs of NPs. Most of NPs show slight toxicity when exposed to animals, while certain toxic effects like oxidative stress generation, inflammation and DNA damage are commonly observed. The severity of NPs toxicity is dependent upon several factors, including exposure dose and administration, NPs chemistry, size, shape, agglomeration state, and electromagnetic properties, which could provide useful information necessary to control the toxicity of NPs. Finally, the safety evaluation of nanotoxicity was addressed.

Transcriptome analysis of different sizes of 3-mercaptopropionic acid-modified cadmium telluride quantum dot-induced toxic effects reveals immune response in rat hippocampus.

Recently, the increasing number of bio-safety assessments on cadmium-containing quantum dots (QDs) suggested that they could lead to detrimental effects on the central nervous system (CNS) of living organisms, but the underlying action mechanisms are still rarely reported. In this study, whole-transcriptome sequencing was performed to analyze the changes in genome-wide gene expression pattern of rat hippocampus after treatments of cadmium telluride (CdTe) QDs with two sizes to understand better the mechanisms of CdTe QDs causing toxic effects in the CNS. We identified 2095 differentially expressed genes (DEGs). Fifty-five DEGs were between the control and 2.2 nm CdTe QDs, 1180 were between the control and 3.5 nm CdTe QDs and 860 were between the two kinds of CdTe QDs. It seemed that the 3.5 nm CdTe QD exposure might elicit severe effects in the rat hippocampus than 2.2 nm CdTe QDs at the transcriptome level. After bioinformatics analysis, we found that most DEG-enriched Gene Ontology subcategories and Kyoto Encyclopedia of Genes and Genomes pathways were related with the immune system process. For example, the Gene Ontology subcategories included immune response, inflammatory response and T-cell proliferation; Kyoto Encyclopedia of Genes and Genomes pathways included NOD/Toll-like receptor signaling pathway, nuclear factor-κB signaling pathway, tumor necrosis factor signaling pathway, natural killer cell-mediated cytotoxicity and T/B-cell receptor signaling pathway. The traditional toxicological examinations confirmed the systemic immune response and CNS inflammation in rats exposed to CdTe QDs. This transcriptome analysis not only revealed the probably molecular mechanisms of CdTe QDs causing neurotoxicity, but also provided references for the further related studies.

Analysis of differentially changed gene expression in EA.hy926 human endothelial cell after exposure of fine particulate matter on the basis of microarray profile.

Epidemiological studies have illustrated that PM2.5 is closely related to cardiovascular disease (CVD), but underlying toxicological mechanisms are not yet clear. The main purpose of this study is to disclose the potential biological mechanisms responsible for PM2.5-dependent adverse cardiovascular outcomes through the appliance of genome-wide transcription microarray. From results, compared with the control group, there are 97 genes significantly altered in 2.5 µg/cm2 PM2.5 treated group and 440 differentially expressed genes in 10 µg/cm2 group. Of note, when 2.5 µg/cm2 and 10 µg/cm2 group were respectively compared with the control group, 46 significantly altered genes showed a consistent tendency in two treated groups, of which 31 genes were upregulated while 15 genes were meanwhile downregulated. Based on Gene Ontology (GO) annotation, altered genes are mainly gathered in functions of cellular processes and immune regulation. Pathway analysis indicated that TNF signaling pathway, NOD-like receptor (NLRs) signaling pathway, MAPK signaling pathway and gap junction are vital pathways involved in PM2.5-induced toxicity in EA.hy926. Moreover, results from RT-qPCR further corroborated that changed genes are implicated in oxidative stress, inflammation and metabolic disorder. In addition, metabolism of xenobiotics by cytochrome P450 pathway is the critical pathway which may serve as a target to prevent PM2.5-induced CVD. To sum up, our effort provides a fundamental data for further studies regarding mechanisms of PM2.5-induced cardiovascular toxicity on the basis of genome-wide screening.

Research advances on potential neurotoxicity of quantum dots.

With rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in biological and biomedical studies, including neuroscience, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs with a growing number of studies. However, the knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, while a potential risk of neurotoxicity arises if mass production of QDs leads to increased exposure and distribution in the nervous system. Owing to the quantum size effect of QDs, they are capable of crossing the blood-brain barrier or moving along neural pathways and entering the brain. Nevertheless, the interactions of QDs with cells and tissues in the central nervous system are not well understood. This review highlighted research advances on the neurotoxicity of QDs in the central nervous system, including oxidative stress injury, elevated cytoplasmic Ca(2+) levels and autophagy to damage in vitro neural cells, and impairments of synaptic transmission and plasticity as well as brain functions in tested animals, with the hope of throwing light on future research directions of QD neurotoxicity, which is a demanding topic that requires further exploration.

Liver Toxicity of Cadmium Telluride Quantum Dots (CdTe QDs) Due to Oxidative Stress in Vitro and in Vivo.

With the applications of quantum dots (QDs) expanding, many studies have described the potential adverse effects of QDs, yet little attention has been paid to potential toxicity of QDs in the liver. The aim of this study was to investigate the effects of cadmium telluride (CdTe) QDs in mice and murine hepatoma cells alpha mouse liver 12 (AML 12). CdTe QDs administration significantly increased the level of lipid peroxides marker malondialdehyde (MDA) in the livers of treated mice. Furthermore, CdTe QDs caused cytotoxicity in AML 12 cells in a dose- and time-dependent manner, which was likely mediated through the generation of reactive oxygen species (ROS) and the induction of apoptosis. An increase in ROS generation with a concomitant increase in the gene expression of the tumor suppressor gene p53, the pro-apoptotic gene Bcl-2 and a decrease in the anti-apoptosis gene Bax, suggested that a mitochondria mediated pathway was involved in CdTe QDs' induced apoptosis. Finally, we showed that NF-E2-related factor 2 (Nrf2) deficiency blocked induced oxidative stress to protect cells from injury induced by CdTe QDs. These findings provide insights into the regulatory mechanisms involved in the activation of Nrf2 signaling that confers protection against CdTe QDs-induced apoptosis in hepatocytes.

[Research on advance of health effects of nanoparticles on air pollution in China].

The adverse health effects of fine particles in the air pollution has been confirmed, and health consequences induced by ultrafine particles (mass media aerodynamic diameter < 0.1 micrometer), which was also known as nanoparticles, was drawing an increasing attention by researchers. Firstly, this review discussed the sources and physicochemical characteristics of nanoparticles in the atmosphere in China. And then we focused on the biological effects and potential toxicity mechanisms of some common nanoparticles in the atmosphere on the major tissues and organs. Finally, the research focus of the nano particles in air pollutants was also presented.