Silver nanoparticles induced synaptic degeneration via Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells.

Silver nanoparticles (AgNPs) have been widely used in biomedicine and cosmetics, increasing their potential risks in neurotoxicity. But the involved molecular mechanism remains unclear. This study aims to explore molecular events related to AgNPs-induced neuronal damage by RNA-seq, and elucidate the role of Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells synaptic degeneration induced by AgNPs. This study found that cell viabilities were decreased by AgNPs in a dose/time-dependent manner. AgNPs also increased protein expression of PINK1, Parkin, synaptophysin, and inhibited PGC-1α, MAP2 and APP protein expression, indicating AgNPs-induced synaptic degeneration involved in disturbance of mitophagy and mitochondrial biogenesis in HT22 cells. Moreover, inhibition of AgNPs-induced Ca2+/CaMKII activation and Drp1/ROS rescued mitophagy disturbance and synaptic degeneration in HT22 cells by reserving aforementioned protein express changes except for PGC-1α and APP protein. Thus, AgNPs-induced synaptic degeneration was mediated by Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells, and mitophagy is the sensitive to the mechanism. Our study will provide in-depth molecular mechanism data for neurotoxic evaluation and biomedical application of AgNPs.

Comparative oxidative damages induced by silver nanoparticles with different sizes and coatings in Caenorhabditis elegans.

Silver nanoparticles (AgNPs) are widely used in many commercial and medical products. Serious concerns are paid on their adverse potentials to the environment and human health. In this study, toxic effects and oxidative stress induced by AgNPs with different sizes and coatings (20 nm AgNPs, 20 nm polyvinylpyrrolidone (PVP) -AgNPs and 50 nm AgNPs) in Caenorhabditis elegans (C. elegans) were investigated. The toxic effects including the shortened lifespan and decreased frequency of head thrashes and body bends of C. elegans were induced in a dose-dependent manner by AgNPs. The reactive oxygen species (ROS) production and the oxidative stress-related indicators including malondialdehyde (MDA) and glutathione (GSH) in nematodes were changed after exposure to three kinds of AgNPs. These effects were the most obvious in a 20 nm PVP-AgNPs exposure group. AgNPs could also induce the expression of genes related to oxidative stress in nematodes. In addition, the up-regulation of mtl-1 and mtl-2 in nematodes might reduce the oxidative damage caused by AgNPs, by using transgenic strains CF2222 and CL2120 nematodes. Metallothionein (MT), an antioxidant, could relieve the oxidative damage caused by AgNPs. These results suggested that 20 nm PVP-AgNPs with a smaller particle size and better dispersion have stronger toxic effects and the oxidative damage to nematodes. Mtl-1 and mtl-2 might be involved in alleviating the oxidative damage caused by AgNPs. Our findings provide clues for the safety evaluation and mechanism information of metal nanoparticles.

ROS-Drp1-mediated mitochondria fission contributes to hippocampal HT22 cell apoptosis induced by silver nanoparticles.

Silver nanoparticles (AgNPs) have widely used in industrial and medical applications for their excellent antibacterial activities. AgNPs can penetrate into the brain and cause neuronal death, but limited evidence focused on toxic effects and mechanic study in hippocampal neuron. This study aimed to investigate the molecular mechanisms of mitochondrial damage and apoptosis in mouse hippocampal HT22 cells and further to explore role of reactive oxygen species (ROS) and GTPase dynamin-related protein 1 (Drp1) in AgNPs-induced neurotoxicity. Our results showed that acute exposure to AgNPs at low doses (2-8 µg/mL) increased ROS generation, decreased mitochondrial membrane potential (MMP) and ATP synthesis in HT22 cells. In addition, AgNPs promoted mitochondrial fragmentation and mitochondria-dependent apoptosis via excessive mitochondrial fission/fusion by 8 µg/mL AgNPs treatment for 24 h. The mechanism was involved in increased protein expression of Drp1, mitochondrial fission protein 1 (Fis1), mitofusin 1/2 (Mfn1/2) and inhibited optic atrophy 1 (OPA1), and mainly mediated by phosphorylation of Drp1 Ser616. The AgNPs-induced mitochondrial impairment and apoptosis was mainly due to their particle-specific effect rather than silver ions release. Furthermore Drp1-mediated mitochondrial fission contributed to mitochondria-dependent apoptosis induced by AgNPs, all aforementioned changes were significantly rescued by N-acetyl-l-cysteine (NAC) and Mdivi-1 except for OPA1 protein expression. Hence, our results provide a novel neurotoxic mechanism to AgNPs-induced neurotoxicity and revealed that the mechanism of mitochondria-dependent apoptosis in HT22 cells was mediated by excessive activation of ROS-Drp1-mitochondrial fission axis. These findings can deepen current evidences on neurotoxicological evaluation of AgNPs and aid in guiding their proper applications in different areas, especially in biomedical use.

ROS and DRP1 interactions accelerate the mitochondrial injury induced by polystyrene nanoplastics in human liver HepG2 cells.

Microplastics have become a serious environmental pollutant and subsequently have harmful effects on human health. Thus, the impacts of microplastics on human cells need to be explored. In the present study, the cytotoxic effects at the subcellular-organelle levels to polystyrene nanoplastics (PS-NPs, diameter 21.5 ± 2.7 nm) were investigated in the human hepatocellular carcinoma (HepG2) cell line. The cell viability exposed to PS-NPs at the concentrations of 6.25, 12.5, 25 and 50 µg/mL for 24 h diminished in a concentration-dependent manner. The PS-NPs treatment induced mitochondrial injuries, including morphological changes, decreased adenosine triphosphate (ATP) production and the loss of mitochondrial membrane potentials (MMP). The PS-NPs treatment could further spark cell apoptosis by upregulating caspase 3, caspase 9, cytochrome c, and Bcl-2 associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) in HepG2 cells, which is related to the mitochondrial dysfunction. PS-NPs exposure stimulated the excessive cellular reactive oxygen species (ROS) production and also induced mitochondrial fission by upregulating dynamin-related protein 1 (DRP1) and P-DRP1, but downregulating optic atrophy protein 1 (OPA1) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) expression levels. The above effects on mitochondria damage induced by PS-NPs were reversed by the pretreatment of N-acetylcysteine (NAC), mitochondrial division inhibitor 1 (Mdivi-1) and DRP1 siRNA. The results suggested that the interaction between ROS and DRP1-dependent mitochondrial division could promote mitochondrial lesions and mitochondria-related apoptosis caused by PS-NPs. These findings on molecular mechanisms provide a theoretical basis for preventing the hazards caused by microplastics to human health.

Adaptive regulations of Nrf2 alleviates silver nanoparticles-induced oxidative stress-related liver cells injury.

Silver nanoparticles (AgNPs) are widely used in various fields such as industry, agriculture, and medical care because of their excellent broad-spectrum antibacterial activity. However, their extensive use has raised concerns about their health risks. Liver is one of the main target organs for the accumulation and action of AgNPs. Therefore, evaluating the toxic effects of AgNPs on liver cells and its mechanisms of action is crucial for the safe application of AgNPs. In the study, polyvinylpyrrolidone (PVP)-coated AgNPs were characterized. The human hepatoma cell line (HepG2) and the normal hepatic cell line (L02) were exposed to different concentrations of AgNPs (20-160 µg/mL) and pretreated with the addition of N-acetylcysteine (NAC) or by Nrf2 siRNA transfection. NAC was able to inhibit the concentration-dependent increase in the level of apoptosis induced by AgNPs in HepG2 cells and L02 cells. Interestingly, HepG2 cells were more sensitive to AgNPs than L02 cells, and this may be related to the different ROS generation and responses to AgNPs by cancer cells and normal cells. In addition, NAC also alleviated the imbalance of antioxidant system and cell cycle arrest, which may be related to AgNPs-induced DNA damage and autophagy. The knockdown of nuclear factor erythroid-derived factor 2-related factor (Nrf2) found that AgNPs-induced ROS and apoptosis levels were further upregulated, but the cell cycle arrest was alleviated. On the whole, Nrf2 exerts a protective role in AgNPs-induced hepatotoxicity. This study complements the hepatotoxicity mechanisms of AgNPs and provides data for a future exploration of AgNPs-related anti-hepatocellular carcinoma drugs.

Silver nanoparticle-induced impaired autophagic flux and lysosomal dysfunction contribute to the microglia inflammation polarization.

Silver nanoparticles (AgNPs) have been incorporated in many consumer and biomedical products. Serious concerns have been expressed about the environmental and public health risks caused by nanoparticles. In previous studies, we found that AgNPs induced microglia polarization of the inflammatory phenotype. Autophagy was a critical for AgNPs-induced neuroinflammation. In the present study, we evaluated in detail the effects of AgNPs in different stages of the autophagy process, and we found that AgNPs induced neuroinflammatory responses and autophagic flux blockage both in the mouse brain and BV2 cells. AgNPs inhibited autophagosome-lysosome fusion and impaired the lysosomal functions by reducing the levels of lysosomal-associated membrane proteins, promoting lysosome membrane permeability and altering the lysosomal acidic microenvironment. These changes resulted in the defects in autophagic substrate clearance and subsequently led neuroinflammation. In addition, the elevation of autophagy could prevent the neuroinflammation induced by AgNPs. As a result, AgNPs hindered autophagic flux by inhibiting autophagosome fusion with lysosomes, thus aggravating the AgNPs-induced neurotoxicity. These findings will provide new insights to investigate the molecular mechanisms of neurotoxicity caused by AgNPs.

Silver nanoparticles induced hippocampal neuronal damage involved in mitophagy, mitochondrial biogenesis and synaptic degeneration.

Silver nanoparticles (AgNPs) could accumulate in the central nervous system (CNS) and induce neurotoxicity for their widespread use in industry and medicine. Mitochondria are vulnerable to toxicity of AgNPs, however, their role in the neurotoxicity remains unclear. This study aimed to evaluate AgNPs-induced synaptic degeneration in mouse hippocampal neurons (at a dose of 12-120 mg/kg BW via intravenous injection), and to further investigate mechanism of mitophagy, mitochondrial biogenesis process in the neurotoxicity. The results indicated that AgNPs accumulated in mouse hippocampal neurons and induced neurological deficits of learning and memory, which involved in synaptic degeneration accompanied with mitochondrial damage. Mechanistically, AgNPs exposure increased protein expression of PTEN-induced kinase 1 (PINK1), Parkin and inhibited peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) protein expression, caused disturbed mitophagy and mitochondrial biogenesis. AgNPs also induced synaptic damage by increasing the protein expression of synaptophysin and decreasing PSD95, MAP2 protein expression. AgNPs exposure even promoted protein expression of amyloid precursor protein (APP) using in amyloid-ß (Aß) cleavage. Furthermore, AgNPs induced hippocampal neuronal synaptic degeneration, mitophagy and mitochondrial biogenesis is dependent on particle-specific AgNPs rather than released silver ions. Our research could provide insights into the regulatory mechanisms of AgNPs-induced neurotoxicity. This study will shed the light of neurotoxicological evaluation of nanoparticles and possible early warning of biomedical applications.

Urban fine particulate matter causes cardiac hypertrophy through calcium-mediated mitochondrial bioenergetics dysfunction in mice hearts and human cardiomyocytes.

In recent years, the cardiovascular toxicity of urban fine particulate matter (PM2.5) has sparked significant alarm. Mitochondria produce 90% of ATP and make up 30% of the volume of cardiomyocytes. Thus knowledge of myocardial mitochondrial dysfunction due to PM2.5 exposure is essential for further cardiotoxic effects. Here, the mechanism of PM2.5-induced cardiac hypertrophy through calcium overload and mitochondrial dysfunction was investigated in vivo and in vitro. Male and female BALB/c mice were given 1.28, 5.5, and 11 mg PM2.5/kg bodyweight weekly through oropharyngeal inhalation for four weeks and were assigned to low, medium, and high dose groups, respectively. PM2.5-induced myocardial edema and cardiac hypertrophy were detected in the high-dose group. Mitochondria were scattered and ruptured with abnormal ultrastructural morphology. In vitro experiments on human cardiomyocyte AC16 showed that exposure to PM2.5 for 24 h caused opened mitochondrial permeability transition pore --leading to excessive calcium production, decreased mitochondrial membrane potential, weakened mitochondrial respiratory metabolism capacity, and decreased ATP production. Nevertheless, the administration of calcium chelator ameliorated the mitochondrial damage in the PM2.5-treated group. Our in vivo and in vitro results confirmed that calcium overload under PM2.5 exposure triggered mTOR/AKT/GSK-3ß activation, leading to mitochondrial bioenergetics dysfunction and cardiac hypertrophy.

Intermittent exposure to airborne particulate matter induces subcellular dysfunction and aortic cell damage in BALB/c mice through multi-endpoint assessment at environmentally relevant concentrations.

Airborne particulate matter (PM) has been linked to cardiovascular diseases, but the underlying mechanisms remain unclear, especially at realistic exposure levels. In this study, both male and female BALB/c mice were employed to assess vascular homeostasis following a standard urban particulate matter, PM SRM1648a, via oropharyngeal aspiration at three environmentally relevant concentrations. The tested indicators included histopathological observation and lipid deposition, as well as redox biology and inflammatory responses. Furthermore, endothelial monolayer, vascular cell apoptosis and subcellular function were assessed to decipher whether episodic PM SRM1648a exposure leads to vascular damage after multiple periods of treatment, including subacute (4 weeks) and subchronic (8 weeks) durations. As a result, PM aspiration caused thickening of airways, leukocytes infiltration and adhesion to alveoli, with the spot of particles engulfed by pulmonary macrophages. Meanwhile, it induced local and systemic oxidative stress and inflammation, but limited pathological changes were captured throughout aortic tissues after either subacute or subchronic treatment. Furthermore, even in the absence of aortic impairment, vascular cell equilibrium has been disturbed by the characteristics of endothelial monolayer disintegration and cell apoptosis. Mechanistically, PM SRM1648a activated molecular markers of ER stress (BIP) and mitochondrial dynamics (DRP1) at both transcriptional and translational levels, which were strongly correlated to ox-inflammation and could serve as early checkpoints of hazardous events. In summary, our data basically indicate that episodic exposure of BALB/c mice to PM SRM1648a exerts limited effects on vascular histopathological alterations, but induces vascular cell apoptosis and subcellular dysfunction, to which local and systemic redox biology and inflammation are probably correlated.

The crosstalk between DRP1-dependent mitochondrial fission and oxidative stress triggers hepatocyte apoptosis induced by silver nanoparticles.

Previous studies have revealed that the liver is the main target organ of deposition for engineered nanoparticles. The hepatotoxicity of silver nanoparticles (AgNPs), the widely used antimicrobial nanoparticles, has been of great interest. However, little is known about the regulatory mechanism of the mitochondria in AgNP-induced hepatotoxicity. In the present study, we found that AgNPs, rather than silver ions, induced mitochondrial dynamics disorders, oxidative stress, and mitochondria-dependent hepatocyte apoptosis in mice. Using human hepatocellular carcinoma (HepG2) cells, we confirmed that the interaction between dynamin-related protein 1 (DRP1)-dependent mitochondrial fission and oxidative stress promoted mitochondrial damage and mitochondria-dependent apoptosis induced by AgNPs, as determined by the elimination of DRP1 or addition of N-acetylcysteine (NAC). Interestingly, the crosstalk between DRP1-dependent mitochondrial fission and oxidative stress also activated mitophagy and autophagy flux blocking. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) gene silencing contributed to the aggravation of mitochondrial damage, oxidative stress, and apoptosis. These results revealed that the interplay between mitochondrial fission and oxidative stress induced mitophagy defects and triggered AgNP-induced mitochondria-dependent apoptosis in liver cells both in vivo and in vitro. Our findings provide a perspective for the mechanism of hepatotoxicity induced by exposure to metal NPs.

The key role of autophagy in silver nanoparticle-induced BV2 cells inflammation and polarization.

As the release of silver nanoparticles (AgNPs) in the environment continues to increase, great concerns have been raised about their potential toxicity to humans. It is urgent to assess the possible toxicity of AgNPs to the immune cells of the central nervous system due to the continuous accumulation of AgNPs in the brain. This study aimed to evaluate the neurotoxicity of AgNPs and the regulatory mechanism of autophagy in AgNPs-induced inflammation by using mouse microglia BV2 cell lines. AgNPs decreased the microglia cell activity in a concentration and time-dependent manner. The exposure of BV2 cells to AgNPs at a non-cytotoxic level of 5 µg/mL resulted in increase of pro-inflammatory cytokines and decrease of mRNA expression of anti-inflammatory cytokines. AgNPs exposure increased M1 markers of iNOS expression and decreased the expression of M2 markers of CD206 in a time-dependent manner. Meanwhile, the expression of inflammatory proteins IL-1ß and NF-κB increased significantly. Additionally, AgNPs induced an increase in autophagosome and upregulation of LC3II, Beclin1, and p62 expression levels. Pretreatment by an autophagy inhibitor, 3-Methyladenine, caused more AgNPs-treated microglia to polarized into pro-inflammatory phenotypes. Inhibition of autophagy also increased the expression of inflammation-associated mRNA and proteins in BV2 cells. These results indicated that AgNPs could induce pro-inflammatory phenotypic polarization of microglia and the autophagy could play a key regulatory role in the pro-inflammatory phenotypic polarization of microglia induced by AgNPs.

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.

Silver nanoparticles induced cytotoxicity in HT22 cells through autophagy and apoptosis via PI3K/AKT/mTOR signaling pathway.

With the widespread application and inevitable environmental exposure, silver nanoparticles (AgNPs) can be accumulated in various organs. More serious concerns are raised on the biological safety and potential toxicity of AgNPs in the central nervous system (CNS), especially in the hippocampus. This study aimed to investigate the biological effects and the role of PI3K/AKT/mTOR signaling pathway in AgNPs mediated cytotoxicity using the mouse hippocampal neuronal cell line (HT22 cells). AgNPs reduced cell viability and induced membrane leakage in a dose-dependent manner, determined by the MTT and LDH assay. In doses of 25, 50, 100 µg mL-1 for 24 h, AgNPs promoted the excessive production of reactive oxygen species (ROS) and caused the oxidative stress in HT22 cells. AgNPs induced autophagy, determined by the transmission electron microscopy observation, upregulation of LC3 II/I and downregulation of p62 expression levels. The mechanistic investigation showed that the PI3K/AKT/mTOR signaling pathway was activated by phosphorylation, which was enrolled in an AgNP-induced autophagy process. AgNPs could further trigger the apoptosis by upregulation of caspase-3 and Bax and downregulation of Bcl-2 in HT22 cells. These results revealed AgNP-induced cytotoxicity in HT22 cells, which was mediated by autophagy and apoptosis via the PI3K/AKT/mTOR signaling pathway. The study could provide the experimental evidence and explanation for the potential neurotoxicity triggered by AgNPs in vitro.

Neurotoxicity of metal-containing nanoparticles and implications in glial cells.

With the development of nanotechnology, metal-containing nanoparticles are used widely in the diagnosis, monitoring and treatment of central nervous system (CNS) diseases. The neurotoxicity of these nanoparticles has drawn attention. Glial cells (particularly microglial cells and astrocytes) have important functions in the CNS. Neural disorders are related to functional/histologic damage to glial cells. Dysfunctions of microglial cells or astrocytes injure the brain, and cause the neurodegeneration seen in Alzheimer's disease and Parkinson's disease. We have summarized the route of access of metal-containing nanoparticles to the CNS, as well as their neurotoxicity and potential molecular mechanisms involved in glial cells. Metal-containing nanoparticles cross or bypass the blood-brain barrier, access the CNS and cause neurotoxicity. The potential mechanisms are related to inflammation, oxidative stress, DNA and/or mitochondrial damage and cell death, all of which are mediated by microglial cell activation, inflammatory factor release, generation of reactive oxygen species, apoptosis and/or autophagy in glial cells. Moreover, these processes increase the burden of the CNS and even accelerate the occurrence or development of neurodegenerative diseases. Some important signaling pathways involved in the mechanism of neurotoxicity in glial cells caused by nanoparticles are also discussed.

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.

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.

Potential health impact of environmental micro- and nanoplastics pollution.

Micro- and nanoplastics are generated from plastics and have negative impacts on the environment due to their high level of fragmentation. They can originate from various sources such as fragments, fibers and foams. The large proportion of the waste and resistance to degradation means micro- and nanoplastics have become a serious global environmental problem, but there are few studies on their potential toxicity for human health. In this review, we discussed routes of exposure and the potential effects of micro- and nanoplastics to human health. Human beings could mainly be exposed to micro- and nanoplastics orally and by inhalation. The possible toxic effects of plastic particles are due to the potential toxicity of plastics themselves, and their combined toxicity with leachable additives and adsorbed contaminants. The potential risks for human health focused on their gastrointestinal toxicity and liver toxicity. The toxic mechanisms could involve oxidative stress, inflammatory reactions and metabolism disorders. More studies are needed to carry out and explore the potential toxicological mechanisms of micro- and nanoplastics and evaluate the combined toxicity of their adsorbed contaminants.

Silver nanoparticles modulate mitochondrial dynamics and biogenesis in HepG2 cells.

Silver nanoparticles (AgNPs) are inevitably released into the environment owing to their widespread applications in industry and medicine. The potential of their toxicity has aroused a great concern. Previous studies have shown that AgNPs exposure in HepG2 cells is primarily related to the damage of mitochondria, which includes induction of mitochondrial swelling and increase of intracellular levels of reactive oxygen species (ROS), the collapse of mitochondrial membrane potential and induction of apoptosis through a mitochondrial pathway. In this study, the effects of AgNPs exposure in HepG2 cells on mitochondrial dynamics and biogenesis were investigated. AgNPs were found to induce mitochondrial morphological and structural alterations. The expressions of key proteins (Drp1, Fis1, OPA1, Mff, Mfn1, and Mfn2) related to mitochondrial fission/fusion event were changed. Especially the expression of fission-related protein 1 (p-Drp1) (Ser616) was significantly up-regulated, whereas the expression of mitochondrial biogenesis protein (PGC-1α) was reduced in AgNP-treated cells. Concomitantly, the expression of autophagy marker proteins (LC3B and p62) was increased. The results suggested that AgNPs could trigger cytotoxicity by targeting the mitochondria, resulting in the disruption of mitochondrial function, damage to the mitochondrial structure and morphology, interfering in mitochondrial dynamics and biogenesis. The mitochondria could be a critical target of AgNPs in cells. The functions of mitochondria could be used for assessing the cytotoxic effects associated with AgNPs in cells.

The impact on T-regulatory cell related immune responses in rural women exposed to polycyclic aromatic hydrocarbons (PAHs) in household air pollution in Gansu, China: A pilot investigation.

Previous studies found associations between impairments of immune functions and exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient air pollution in the U. S. and China. However, the results remain inconclusive due to the limitations of these studies. In this study, we aimed to examine the direction and magnitude of immune changes related to PAH exposure from household air pollution among rural women living in Gansu, China. Healthy village women (n = 34) were recruited and enrolled in the study. Questionnaires were administered. Blood and urine samples were collected and analyzed during non-heating (September 2017, "summer") and heating (January 2018, "winter") seasons. Urinary 1-hydroxypyrene (1-OHP) was quantified as the biomarker of PAH exposure. To evaluate Treg cell related immune functions, we examined immunoglobulin E (IgE), percent of T-regulatory (Treg) cells, and gene expression of following: forkhead box transcription factor 3 (Foxp3), transforming growth factor-ß (TGF-ß), interleukin 10 (IL-10), and interleukin 35 (IL-35), composed of interleukin-12 alpha (IL-12α) and Epstein-Barr-virus-induced gene 3 (EBi3). Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to evaluate oxidative DNA damage. The results showed that the concentration of 1-OHP increased from 0.90 to 17.4 µmol mol-Cr -1 from summer to winter (p < 0.001). Meanwhile, average percent of Treg cells decreased from 5.01% to 1.15% (p < 0.001); IgE and mRNA expressions of Foxp3, TGF-ß, IL-10, IL-12α and EBi3 all significantly decreased (p < 0.001); Urinary 8-OHdG increased from 12.7 to 30.3 ng mg-Cr -1 (p < 0.001). The changes in 8-OHdG, Foxp3 and TGF-ß were significantly associated with the increase of 1-OHP. The results suggested that we observed a substantial increase of PAH exposure in winter, which was significantly associated with the repression on Treg cell function and oxidative DNA damage. Exposure to PAHs in household air pollution possibly induced immune impairments among rural women in northwest China.