Aijie Chen

Central nervous system toxicity of metallic nanoparticles.

Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed.

Application of dental nanomaterials: potential toxicity to the central nervous system

Nanomaterials are defined as materials with one or more external dimensions with a size of 1–100 nm. Such materials possess typical nanostructure-dependent properties (eg, chemical, biological, optical, mechanical, and magnetic), which may differ greatly from the properties of their bulk counterparts. In recent years, nanomaterials have been widely used in the production of dental materials, particularly in light polymerization composite resins and bonding systems, coating materials for dental implants, bioceramics, endodontic sealers, and mouthwashes. However, the dental applications of nanomaterials yield not only a significant improvement in clinical treatments but also growing concerns regarding their biosecurity. The brain is well protected by the blood–brain barrier (BBB), which separates the blood from the cerebral parenchyma. However, in recent years, many studies have found that nanoparticles (NPs), including nanocarriers, can transport through the BBB and locate in the central nervous system (CNS). Because the CNS may be a potential target organ of the nanomaterials, it is essential to determine the neurotoxic effects of NPs. In this review, possible dental nanomaterials and their pathways into the CNS are discussed, as well as related neurotoxicity effects underlying the in vitro and in vivo studies. Finally, we analyze the limitations of the current testing methods on the toxicological effects of nanomaterials. This review contributes to a better understanding of the nano-related risks to the CNS as well as the further development of safety assessment systems.

Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells

With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1−/− BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 μg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity.

Graphene oxide and reduced graphene oxide induced neural pheochromocytoma-derived PC12 cell lines apoptosis and cell cycle alterations via the ERK signaling pathways

Given the novel applications of graphene materials in biomedical and electronics industry, the health hazards of these particles have attracted extensive worldwide attention. Although many studies have been performed on graphene material-induced toxic effects, toxicological data for the effect of graphene materials on the nervous system are lacking. In this study, we focused on the biological effects of graphene oxide (GO) and reduced graphene oxide (rGO) materials on PC12 cells, a type of traditional neural cell line. We found that GO and rGO exerted significant toxic effects on PC12 cells in a dose- and time-dependent manner. Moreover, apoptosis appeared to be a response to toxicity. A potent increase in the number of PC12 cells at G0/G1 phase after GO and rGO exposure was detected by cell cycle analysis. We found that phosphorylation levels of ERK signaling molecules, which are related to cell cycle regulation and apoptosis, were significantly altered after GO and rGO exposure. In conclusion, our results show that GO has more potent toxic effects than rGO and that apoptosis and cell cycle arrest are the main toxicity responses to GO and rGO treatments, which are likely due to ERK pathway regulation.

Evaluation of the effect of time on the distribution of zinc oxide nanoparticles in tissues of rats and mice: a systematic review.

To evaluate the time effect on the distribution of zinc oxide nanoparticles (ZnO NPs) in tissues from rats and mice, a search on the PubMed, Embase, SpringerLink, Scopus, Science Direct, Cochrane, CNKI, Wanfang, and vip databases up to September 2014 was performed, followed by screening, data extraction, and quality assessment. Thirteen studies were included. At 24 h, Zn content was mainly distributed in the liver, kidney, and lung. At ≥7 days, Zn content was mainly distributed in the liver, kidney, lung, and brain. ZnO NPs are readily deposited in tissues. Furthermore, as time increases, Zn content decreases in the liver and kidney, but increases in the brain.

Current understanding of the toxicological risk posed to the fetus following maternal exposure to nanoparticles

ABSTRACT Introduction: With the broad use of nanotechnology, the number and variety of nanoparticles that humans can be exposed to has further increased. Consequently, there is growing concern about the potential effect of maternal exposure to various nanoparticles during pregnancy on a fetus. However, the nature of this risk is not fully known. Areas covered: In this review, materno-fetal transfer of nanoparticles through the placenta is described. Both prenatal and postnatal adverse effects, such as fetal resorption, malformation and injury to various organs in mice exposed to nanoparticles are reviewed. The potential mechanisms of toxicity are also discussed. Expert opinion: The toxicology and safe application of recently developed nanoparticles has attracted much attention in the past few years. Although many studies have demonstrated the toxicology of nanoparticles in various species, only a small number of studies have examined the effect on a fetus after maternal exposure to nanoparticles. This is particularly important, because the developing fetus is especially vulnerable to the toxic effects of nanoparticles during fetal development due to the unique physical stage of the fetus. Nanoparticles may directly or indirectly impair fetal development and growth after maternal exposure to nanoparticles.

Finite element analysis of stress distribution in four different endodontic post systems in a model canine.

To investigate the stress distribution in a maxillary canine restored with each of four different post systems at different levels of alveolar bone loss. Two-dimensional finite element analysis (FEA) was performed by modeling a severely damaged canine with four different post systems: CAD/CAM zirconia, CAD/CAM glass fiber, cast titanium, and cast gold. A force of 100 N was applied to the crown, and the von Mises stresses were obtained. FEA revealed that the CAD/CAM zirconia post system produced the lowest maximum von Mises stress in the dentin layer at 115.8 MPa, while the CAD/CAM glass fiber post produced the highest stress in the dentin at 518.2 MPa. For a severely damaged anterior tooth, a zirconia post system is the best choice while a cast gold post ranks second. The CAD/CAM glass fiber post is least recommended in terms of stress level in the dentin.

An in vitro evaluation of the zirconia surface treatment by mesoporous zirconia coating on its bonding to resin cement

The effect of zirconia surface treatment by mesoporous zirconia coating on the microtensile bond strength (MTBS) between zirconia and resin cement was investigated in this work. 160 zirconia specimens were prepared and divided into four groups according to surface treatments: (1) airborne-particle-abrasion treatment (APA); (2) glass infiltration and hydrofluoric acid treatment (GI+HF); (3) mesoporous zirconia coating (MZ); and (4) no treatment (C). The as-prepared zirconia specimens were bonded using Panavia F2.0 and RelyX Unicem. The MTBS values were tested using a universal testing machine, and data were analyzed using ANOVA and SNK methods (a=0.05). The MTBS values obtained after GI+HF and MZ treatments were significantly higher than those obtained after APA and C treatments (P<0.05), especially for samples cemented with Panavia F2.0. The results reveal that zirconia surface treatments using GI+HF and MZ yield higher bond strength than those using APA or C, regardless of the resin cements.

Finite element analysis to study the effects of using CAD/CAM glass-fiber post system in a severely damaged anterior tooth

To investigate the stress distribution of a severely damaged maxillary anterior tooth restored with a computer-aided design/computer-aided manufacturing (CAD/CAM) glass-fiber post system. Twelve models were fabricated with different alveolar bone levels and cervical dentin wall thicknesses and studied using a two-dimensional finite element method. A force of 100 N was applied to the lingual surface of the crown at 45 degrees, and the maximum von Mises stress was calculated. A higher stress level was observed in the dentin than in the post and crown. With the reduction of dentin thickness, the maximum von Mises stress in the dentin increased slightly to a peak at a thickness of 1.5 mm, followed by a slight decrease at a thickness of 1.0 mm. However, the relative ratio (RR) values did not show a large difference (RR > 80%). Meanwhile, a large difference in RR values was observed with a change in bone level (RR < 80%). When using a CAD/CAM glass-fiber post system, the maximal von Mises stress was significantly affected by the bone level, rather than by the dentin thickness. Moreover, this system may be applied to the treatment of a maxillary anterior tooth with a bone level of only 2/3.

The toxicity of silica nanoparticles to the immune system

Silicon-based materials and their oxides are widely used in drug delivery, dietary supplements, implants and dental fillers. Silica nanoparticles (SiNPs) interact with immunocompetent cells and induce immunotoxicity. However, the toxic effects of SiNPs on the immune system have been inadequately reviewed. The toxicity of SiNPs to the immune system depends on their physicochemical properties and the cell type. Assessments of immunotoxicity include determining cell dysfunctions, cytotoxicity and genotoxicity. This review focuses on the immunotoxicity of SiNPs and investigates the underlying mechanisms. The main mechanisms were proinflammatory responses, oxidative stress and autophagy. Considering the toxicity of SiNPs, surface and shape modifications may mitigate the toxic effects of SiNPs, providing a new way to produce these nanomaterials with less toxic impaction.