Transcriptomics-based investigation of manganese dioxide nanoparticle toxicity in rats' choroid plexus.

Manganese dioxide nanoparticles (MnO2-NPs) have a wide range of applications in biomedicine. Given this widespread usage, it is worth noting that MnO2-NPs are definitely toxic, especially to the brain. However, the damage caused by MnO2-NPs to the choroid plexus (CP) and to the brain after crossing CP epithelial cells has not been elucidated. Therefore, this study aims to investigate these effects and elucidate potential underlying mechanisms through transcriptomics analysis. To achieve this objective, eighteen SD rats were randomly divided into three groups: the control group (control), low-dose exposure group (low-dose) and high-dose exposure group (high-dose). Animals in the two treated groups were administered with two concentrations of MnO2-NPs (200 mg kg-1 BW and 400 mg kg-1 BW) using a noninvasive intratracheal injection method once a week for three months. Finally, the neural behavior of all the animals was tested using a hot plate tester, open-field test and Y-type electric maze. The morphological characteristics of the CP and hippocampus were observed by H&E stain, and the transcriptome of CP tissues was analysed by transcriptome sequencing. The representative differentially expressed genes were quantified by qRT-PCR. We found that treatment with MnO2-NPs could induce learning capacity and memory faculty decline and destroy the structure of hippocampal and CP cells in rats. High doses of MnO2-NPs had a more obvious destructive capacity. For transcriptomic analysis, we found that there were significant differences in the numbers and types of differential genes in CP between the low- and high-dose groups compared to the control. Through GO terms and KEGG analysis, high-dose MnO2-NPs significantly affected the expression of transporters, ion channel proteins, and ribosomal proteins. There were 17 common differentially expressed genes. Most of them were transporter and binding genes on the cell membrane, and some of them had kinase activity. Three genes, Brinp, Synpr and Crmp1, were selected for qRT-PCR to confirm their expression differences among the three groups. In conclusion, high-dose MnO2-NPs exposure induced abnormal neurobehaviour, impaired memory function, destroyed the structure of the CP and changed its transcriptome in rats. The most significant DEGs in the CP were within the transport system.

Ecological and health risk assessment of heavy metals in soil and Chinese herbal medicines.

As medicinal plants can accumulate harmful metals from the native soil, people's consumption of these materials may cause the human body to accumulate toxic metal elements. This has given rise to people's concerns about the quality and safety of Chinese medicinal materials. This research aims to determine the levels of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb in four medicinal plant species (Aster tataricus L.f., Salvia miltiorrhiza Bge, Radix Aucklandiae, Scutellaria baicalensis Georgi) and their native soil. All samples were collected from Qian'an city, beside Yanshan Mountain Range in Tangshan city, east Hebei Province, north China. The contents of heavy metals we detected in the soil conformed to the current limits. However, the Cd and Hg in the soil had a very high potential ecological risk because of their contents higher than the base level of local soil. The contents of Cu, Cd, Hg and Pb in some medicinal herbs exceeded the standards. The content of Cu in Radix Aucklandiae exceeded the standard by 3 times, and others exceeded the standard by less than one time. The comprehensive health risk assessment of heavy metals with chronic non-carcinogenic effects for human body showed that none of the four medicinal herbs can create a health risk. Thus, there is no strong positive correlation between heavy metal pollution in medicinal herbs and that in the native soil. Further research should be investigated to the connection between the heavy metal levels in the soil and plants, and the comprehensive effects of soil, air and irrigation water on heavy metal pollution of Chinese herbal medicines. We also recommend that Chinese herbal medicines should be cultivated and gathered only from controlled or uncontaminated areas.

Protective effect of astaxanthin against La2O3 nanoparticles induced neurotoxicity by activating PI3K/AKT/Nrf-2 signaling in mice.

Lanthanum oxide nanoparticles (La2O3 NPs) are used in photoelectric and catalytic applications. Astaxanthin (ASX) is a red carotenoid pigment with antioxidant and anti-inflammatory properties, and the antioxidant activities promote neuroprotection. This study explored the effect of ASX supplementation on La2O3 NP-induced neurotoxicity in mice and the molecular mechanisms of such protective effects. Amongst our findings, we determined that ASX treatment significantly attenuated La2O3 NP-induced behavioural abnormalities, histopathological evidence of hippocampal injury and ultrastructural changes in the CA1 region of the hippocampus. ASX treatment also markedly inhibited the production of ROS and activated PI3K/AKT signaling, which facilitated the nuclear translocation of Nrf-2 and reversed the down-regulation of HO-1, NQO1 and GCLM proteins in the hippocampus that were induced by sub-chronic exposure to La2O3 NPs. Administration of ASX to mice receiving La2O3 NPs also resulted in decreased expression of iNOS, IL-1ß, TNF-α, COX-2, Bax and Caspase-3 and in increased expression of BDNF, NGF and Bcl-2 observed in response to La2O3 NPs. In conclusion, ASX had a markedly protective effect against the negative sequelae associated with La2O3 NP-induced neurotoxicity. This may result from the activation of the PI3K/AKT/Nrf-2 signaling and via the inhibition of oxidative stress, neuroinflammation and cellular apoptosis.

Editor's Highlight: Effects of Intraperitoneal Injection of SnS2 Flowers on Mouse Testicle.

SnS2 nanoflowers (SnS2 NFs) have been widely used in photoelectric and catalytic applications. However, its explosure and reproductive toxicity is unknown. The aim of this study was to investigate the effect of exposure to 3 different sized-SnS2 flowers (dose: 38 mg/kg; size: 50, 80, and 200 nm) in testes of mice for 4 weeks by intraperitoneal injection. Though the body weight of mice treated or not with SnS2 NFs was not different, and SnS2 NFs were distributed to the organs including liver, kidney, spleen, heart, brain, and testis, more distribution SnS2 NFs (50 and 80 nm) were found in testicle tissues compared with SnS2 flowers (200 nm) in those tissues. The results of sperm count and survival analysis, histopathological evaluation, and qRT-PCR detection showed that there was moderate reproductive toxicity induced by the small-sized SnS2 NFs in testicle tissues. Furthermore, elevated malondialdehyde level and decreased superoxide dismutase activity were also observed in the SnS2 NFs (dose: 38 mg/kg; size: 50 and 80 nm) treated groups. Likewise, the qRT-PCR data indicated that SnS2 NFs can induce apoptosis and inflammation responses. Although the pro-inflammation marker of TNF-α, IL-1ß, iNOS, and COX-2 at the mRNA levels were higher expression in 50 and 80 nm groups than that in control and 200 nm group, no statistical significance existed between 50 and 80 nm groups. Accordingly, the repeated-dose toxicity of SnS2 NFs in testicle tissues was also observed in a dose-dependent manner by intraperitoneal injection of SnS2 NFs (size: 50 nm; 0.38, 3.8, and 38 mg/kg) for 4 weeks, when determined by sperm count, survival rate, and qRT-PCR analysis. In addition, transmission electron microscopy showed that the ultrastructural abnormalities formed by the small-sized SnS2 NFs in testes were more severe than those formed by the large-sized SnS2 in testes. Taken together, these findings implied that the SnS2 NFs activated inflammation responses that signified apoptosis in murine testes. This study provided useful information for risk analysis and regulation of SnS2 NFs by administration agencies.

Lead selenide nanoparticles-induced oxidative damage of kidney in rats.

OBJECTIVE: To investigate the effect of lead selenide nanoparticles (nano PbSe) on kidney in rats. METHOD: Specific pathogen free SD rats were randomly divided into 4 groups (8 rats/group), and injected with of 0mg/kg (control group), 10mg/kg (low dose group), 20mg/kg (middle dose group), or 30mg/kg (high dose group) nano PbSe respectively. Seven weeks after injection, the serum was taken from rats for the detection of blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA). Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) levels were detected using renal tissue homogenate. Pathological examination was performed on kidney sections. RESULTS: The levels of BUN and Cr in three exposure groups were significantly increased compared with those of control group. Levels of UA in middle dose and high dose group were higher than those in the control group. Levels of SOD, GSH-Px and T-AOC in three exposure groups were markedly decreased compared with those in the control group. Levels of MDA in three exposure groups were higher than those in the control group. Pathological changes at different levels of kidneys were observed, and the damage was more serious with the increase of concentration. CONCLUSIONS: Nano PbSe can lead to oxidative damage to the kidney, with the toxicity positively correlates to the dosage.

Local anesthetic thoracoscopy for the diagnosis of metastatic pleural melanoma originated from oral malignant melanoma: case report and comments.

BACKGROUND: Oral malignant melanoma (OMM) is an aggressive tumor with very low survival rate and easy to metastasize. Pleural metastatic melanoma via primary OMM is rare. CASE PRESENTATION: In this report, we presented a case of metastatic malignant melanoma of the pleura originated from OMM. A 54-year-old man without primary skin lesion was diagnosed multiple nodular shadows, pleural invasion, and pleural effusion by chest computed tomography (CT). One cyst-form tumor on the tongue base was observed by bronchoscopy, which was diagnosed as OMM by pathological examination and then was resected. After getting the tumor tissues from the pleura by pleural biopsy surgery, the diagnosis of pathological examination was pleural metastatic melanoma. Furthermore, tumor cells displayed a positive immunoreaction for melanocytic markers S100 and HMB-45 combining with positive vimentin and cytokeratin AE1/AE3. The patient was therefore diagnosed with metastatic melanoma of the left pleura and the primary melanoma was OMM. CONCLUSIONS: According to this case, we could draw the conclusion that pleural metastasis from OMM was very rare and thoracoscopy preceded under local anesthesia is an important method for its accurate diagnosis.

Effects of nanocrystalline PbSe on hematopoietic system and bone marrow micronucleus rate of rats.

OBJECTIVE: To investigate the effect of lead selenide nanocrystals on hematopoietic system and bone marrow micronucleus rate of rats. METHOD: Specific pathogen free SD rats were randomly divided into 4 groups (8 rats in each group), and injected with of 0 (control group), 10 (low dose group), 20 (middle dose group), 30 mg/kg (high dose group) nanocrystalline PbSe, respectively. Seven weeks after injection, the blood was taken from rats for routine index detection; the number of micronucleus cells per 1000 polychromatic erythrocyte from bone marrow was counted. RESULTS: White blood cell (WBC), lymphocyte (LYM) count in low dose group rats, and WBC, LYM, granulocyte (GRN), monocytes (MOD) counts in high dose group significantly increased compared to those of control group. LYM% ratio decreased while GRN% ratio increased along with the increase of exposure dosage. Compared with those of the control group, levels of erythrocyte mean corpuscular volume (MCV) in low dose group, hemoglobin (HGB), red blood cell specific volume (HCT), MCV in middle dose group and red blood cell (RBC), HGB, HCT, MCV in high dose group, were markedly decreased. Red blood cell distribution width (RDW), blood platelet (PLT) levels in three exposure groups of were higher than those in control group. Marrow micronucleus test results showed that, the micronucleus rate rise in mid dose and high dose group compared with the control group, suggesting that nanocrystalline PbSe has genetic toxicity on rats. CONCLUSIONS: Nano PbSe can lead to changes in blood routine index and bone marrow micronucleus rate, and its toxicity was positively related to the dosage.

Hepatotoxicity and nephrotoxicity of organic contaminants in wastewater-irrigated soil.

The objective of this study is to investigate the hepatotoxicity and nephrotoxicity of organic contaminants in wastewater-irrigated soil using in vivo and in vitro experiments on mice and rat. Soil samples were collected from a wastewater-irrigated area and groundwater-irrigated area, i.e. clean water-irrigated area as control group. The organic contaminants were extracted using an ultrasonic oscillator. In vivo experiment was performed by contamination of hepatocytes of rat using the organic extract, and comet assay was used to analyse the DNA damage of hepatocytes. For in vitro experiment, mice were first gavaged with extracts, and then the indicators for kidney functions, liver functions and oxidative damage of tissues were investigated. The result shows, for in vitro experiments, compared with clean water-irrigated area groups, the average DNA tailing length for the wastewater-irrigated area group is larger, and for the wastewater-irrigated area groups with extract concentration 0.6 g/ml and 0.9 g/ml, the tailing rate increases significantly (P < 0.05). For in vivo experiments, the change of weight across each group shows no significant difference (P < 0.05). Compared with clean water-irrigated groups, the liver indices have decreased for all groups of the wastewater-irrigated area, while both kidney and liver indices decreased for wastewater-irrigated area high-dose group (P < 0.05 or P < 0.01). The total proteins for wastewater-irrigated low-dose group and Gamma-glutamyl transpeptidase, creatinine for high-dose group all increased (P < 0.01). Compared with the reagent control group, total superoxide dismutase activity of liver for wastewater-irrigated groups and glutathione peroxidase activity for high-dose group, malondialdehyde content all decreased (P < 0.05 or P < 0.01); glutathione peroxidase activity of kidney tissue for wastewater-irrigated high-dose group decreased (P < 0.01). The result shows that the joint toxicity in extracts of wastewater-irrigated soil is able to cause DNA damage of hepatocytes in rats, changes of liver functions in mice and lead to oxidative damage of liver and kidney.

Effects of titania nanoparticles on phosphorus fractions and its release in resuspended sediments under UV irradiation.

Little is known about the effects of nano-TiO(2) on the transformation and transport of phosphorus (P) in resuspended sediments. Chemical sequential extraction was used to investigate P fractions and its release in resuspended sediments under the influence of nano-TiO(2) and UV irradiation. The results showed that the contents of sediment P in all fractions decreased with increasing nano-TiO(2) concentration in UV irradiation, while increased in the dark controls. Furthermore, P release from all fractions was greater in UV irradiation than in the controls. Elevated concentrations (10-50 mg L(-1)) of nano-TiO(2) in UV irradiation significantly facilitated the release of P from organic and Fe oxide fractions, possibly resulting from the partial photo-degradation of organic matter and photochemical transformation of Fe oxides. Apparently, nano-TiO(2) in UV irradiation did not immobilize the loosely sorbed P and reductant soluble P release from the resuspended sediments, possible because (1) some of P released from those fractions were refurnished by the P released from OM; (2) photocatalysis of nano-TiO(2) reduced binding capacity of the resuspended sediments. Our results suggest that the photocatalysis of nano-TiO(2) may offer the potential to regulate the transformation and transport of sediment P in the aquatic environment.

[Effect of tea polypheonls and ascorbic acid on the activity of antioxidant enzymes in rats with experimental silicosis].

To explore the effect of tea polypheonls (TP) combined with ascorbic acid on the activity of antioxidant enzymes of rats induced by silica, the activities of nitric oxide synthase (NOS), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) were determined. Compared with the normal saline control group, the activities of SOD and NOS of the silica-induced group increased (P < 0.05), but the activity of GSH-PX was gradually decreased. The activities of SOD and NOS decreased and GSH-PX increased in the intervention group. It is concluded that TP combined with ascorbic acid can alleviate the abnormal change of antioxidant enzymes in rats induced by silica.