Geyu Liang

Influence of Different Sizes of Titanium Dioxide Nanoparticles on Hepatic and Renal Functions in Rats with Correlation to Oxidative Stress

As titanium dioxide (TiO2) nanoparticles are widely used commercially, the potential effects of TiO2 nanoparticles on humans are a concern. To evaluate the effects of TiO2 nanoparticles on hepatic and renal functions and correlate changes to oxidative stress, Sprague-Dawley rats were treated with TiO2 particles of two different specific surface areas (TiO2-S50: 50 m2/g, and TiO2-S210: 210 m2/g) at 0.5, 5, or 50 mg/kg body weight by intratracheal instillation. After 7 d, TiO2 nanoparticles produced no obvious acute toxicity on hepatic and renal functions. However, superoxide dismutase (SOD) activity of plasma and glutathione peroxidase (GSH-PX) activity of kidney in the low-dose TiO2-S210 group were significantly decreased. After TiO2-S210 exposure, malondialdehyde (MDA) levels of liver and kidney in intermediate and high-dose groups were significantly increased. This change only appeared in liver after TiO2-S50 exposure. Furthermore, SOD activity in liver and kidney and GSH-PX activity in kidney with low TiO2-S210 exposure group were significantly less than with low TiO2-S50. No apparent pathological changes in liver and kidney were observed. Intratracheal exposure to TiO2 nanoparticles may induce oxidative stress in liver and kidney, but does not influence hepatic or renal functions. There was no apparent evidence that TiO2-S210 was more toxic than TiO2-S50. In general, intratracheal exposure to TiO2 did not markedly affect extrapulmonary tissue functions.

Effects of subchronic exposure to multi-walled carbon nanotubes on mice.

Carbon nanotubes have attracted attention not only due to electrical, optical, and mechanical applications but also due to their presence in biological and pharmaceutical products. In this study, modified multi-walled carbon nanotubes (MWCNT) were used as a model to evaluate potential subchronic effects of carbon nanotubes on mice. ICR mice were treated with phosphorylcholine-grafted multi-walled carbon nanotubes (MWCNT-PC) daily for 28 d at 10, 50, or 250 mg/kg by the intraperitoneal (ip) route. Subchronic exposure to MWCNT-PC did not produce any apparent systemic effects in mice. The body weight of the high-dose group was significantly lower than control in male mice, whereas tissue to body weight ratios of liver, spleen, and lung rose significantly with increase of dose of MWCNT-PC. There were significant differences between high-dose exposure and control groups. Accumulation of carbon nanotubes and inflammation response in liver, spleen, and lung were observed in the high-dose exposure group. No systemic toxicity and histopathological changes were found in 10-mg/kg exposure groups. Data in the present study support the view that MWCNT in vivo do not exert apparent marked effects in mice and that MWCNT products are relatively safe for human consumption.

Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

Microcystin-Degrading Activity of an Indigenous Bacterial Strain Stenotrophomonas acidaminiphila MC-LTH2 Isolated from Lake Taihu

Microcystin-LR (MC-LR) and microcystin-RR (MC-RR) produced by harmful cyanobacterial blooms (HCBs) pose substantial threats to the ecosystem and public health due to their potential hepatotoxicity. Degradation of microcystins (MCs) by indigenous bacteria represents a promising method for removing MCs from fresh water without harming the aquatic environment, but only a few microcystin (MC)-degrading bacteria have been isolated and had their mechanisms reported. This study aimed to isolate indigenous bacteria from Lake Taihu, and investigate the capability and mechanism of MC degradation by these bacteria. During a Microcystis bloom, an indigenous MC-degrading bacterium designated MC-LTH2 was successfully isolated from Lake Taihu, and identified as Stenotrophomonas acidaminiphila based on phylogenetic analysis. In the presence of MC-LR together with MC-RR, the strain MC-LTH2 was capable of totally degrading both simultaneously in 8 days, at rates of 3.0 mg/(L⋅d) and 5.6 mg/(L⋅d), respectively. The degradation rates of MCs were dependent on temperature, pH, and initial MC concentration. Adda (3-amino-9-methoxy-2, 6, 8-trimethyl-10-phenyldeca-4, 6-dienoic acid) was detected as an intermediate degradation product of MCs using high performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF-MS). To the best of our knowledge, this is the first report of Stenotrophomonas acidaminiphila capable of degrading two MC analogues and other compounds containing Adda residue completely under various conditions, although the mlrA gene in the strain was not detected. These results indicate the Stenotrophomonas acidaminiphila strain MC-LTH2 possesses a significant potential to be used in bioremediation of water bodies contaminated by MC-LR and MC-RR, and is potentially involved in the degradation of MCs during the disappearance of the HCBs in Lake Taihu.

Pre-Diagnostic Plasma 25-Hydroxyvitamin D Levels and Risk of Non-Melanoma Skin Cancer in Women

Background Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer. Methods We prospectively evaluated the association between baseline plasma 25(OH)D levels and the risk of incident squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) among 4,641 women from the Nurses’ Health Study (NHS) and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results Plasma 25(OH)D levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OH)D had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52–2.80, P for trend <0.0001). We also found a significantly positive association between plasma 25(OH)D levels and SCC risk after adjusting for the same covariates (OR, highest vs. lowest quartile  = 3.77, 95% CI = 1.70–8.36, P for trend  = 0.0002). Conclusion In this prospective study of women, plasma vitamin D levels were positively associated with non-melanoma skin cancer risk. Considering that most circulating vitamin D is due to sun exposure, the positive association between plasma vitamin D and non-melanoma skin cancer is confounded by sun exposure. Our data suggest that one-time measurement of plasma vitamin D levels may reasonably reflect long-term sun exposure and predict the risk of non-melanoma skin cancer.

Chlorpyrifos exposure reduces reproductive capacity owing to a damaging effect on gametogenesis in the nematode Caenorhabditis elegans

Previous studies have revealed that chlorpyrifos exposure adversely affects the reproductive capacity of male rodents. The present study investigated the reproductive toxicity of chlorpyrifos exposure and possible related mechanisms using the nematode Caenorhabditis elegans. L4 nematode larvae were exposed to chlorpyrifos at concentrations of 0.003, 0.03, 0.3 and 3.0 mg l−1 for different durations. In addition to decreased brood size, reduced spermatid size, increased percentage of abnormal spermatids, suppressed spermatid activation and motility of sperm, damaged oocyte morphology, increased numbers of apoptotic cells and unfertilized oocytes were observed in nematodes exposed to various concentrations of chlorpyrifos. Moreover, expression patterns of the genes spe‐10, spe‐15, fer‐1, prg‐1, glp‐1, mlh‐1, cyb‐3, ced‐3, ced‐4 and ced‐9 (which are associated with spermatid size, spermatid activation and morphology, oocyte morphology, oocyte function, and apoptosis) were altered after chlorpyrifos exposure. Therefore, chlorpyrifos exposure may adversely affect fertility in nematodes by influencing both spermatogenesis and oogenesis. Alterations in the expression patterns of genes involved in gametogenesis may explain the corresponding changes in gametogenesis in nematodes exposed to chlorpyrifos. Hence, the model organism Caenorhabditis elegans is recommended for assessment of reproductive toxicity relating to gametogenesis. Copyright

Systemic Immune Effects of Titanium Dioxide Nanoparticles after Repeated Intratracheal Instillation in Rat

The potential immune effects of titanium dioxide nanoparticles (nano-TiO2) are raising concern. Our previous study verified that nano-TiO2 induce local immune response in lung tissue followed by intratracheal instillation administration. In this study, we aim to evaluate the systemic immune effects of nano-TiO2. Sprague Dawley rats were treated by intratracheal instillation with nano-TiO2 at doses of 0.5, 4, and 32 mg/kg body weight, micro-TiO2 with 32 mg/kg body weight and 0.9% NaCl, respectively. The exposure was conducted twice a week, for four consecutive weeks. Histopathological immune organs from exposed animals showed slight congestion in spleen, generally brown particulate deposition in cervical and axillary lymph node. Furthermore, immune function response was characterized by increased proliferation of T cells and B cells following mitogen stimulation and enhanced natural killer (NK) cell killing activity in spleen, accompanying by increased number of B cells in blood. No significant changes of Th1-type cytokines (IL-2 and INF-γ) and Th2-type cytokines (TNF-α and IL-6) were observed. Intratracheal exposure to nano-TiO2 may be one of triggers to be responsible for the systemic immune response. Further study is needed to confirm long-lasting lymphocyte responses and the potential mechanisms.

Integrated analysis of long non-coding RNA‑associatedceRNA network reveals potential lncRNA biomarkers in human lung adenocarcinoma

Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer specific lncRNAs in lncRNA-related ceRNA network of lung adenocarcinoma (LUAD) are still unclear. In the present study, the 465 RNA sequencing profiles in LUAD patients were obtained from the cancer genome atlas (TCGA) database, which provides large sample RNA sequencing data free of charge, and 41 cancer specific lncRNAs, 25 miRNAs and 1053 mRNAs (fold change >2, p<0.05) were identified. Then, the lncRNA-miRNA-mRNA ceRNA network of LUAD was constructed with 29 key lncRNAs, 24 miRNAs and 72 mRNAs. Subsequently, we selected these 29 key lncRNAs to analyze their correlation with clinical features, and 21 of them were aberrantly expressed with tumor pathological stage, TNM staging system, lymph node metastasis and patient outcome assessment, respectively. Furthermore, there were 5 lncRNAs (BCRP3, LINC00472, CHIAP2, BMS1P20 and UNQ6494) positively correlated with overall survival (OS, log-rank p<0.05). Finally, 7 cancer specific lncRNAs were randomly selected to verify the expression in 53 newly diagnosed LUAD patients using qRT-PCR. The expression results between TCGA and qRT-PCR were 100% in agreement. The correlation between AFAP1-AS1 and LINC00472 and clinical features were also confirmed. Thus, our results showed the lncRNA expression profiles and we constructed an lncRNA-miRNA-mRNA ceRNA network in LUAD. The present study provides novel insight for better understanding of lncRNA-related ceRNA network in LUAD and facilitates the identification of potential biomarkers for diagnosis and prognosis.

Functional alterations in the glutathione S-transferase family associated with enhanced occurrence of esophageal carcinoma in China.

Glutathione S-transferases (GST) belong to a superfamily of phase II enzymes believed to be associated with enhanced frequency of esophageal carcinoma. This study was performed to evaluate whether the GST family was associated with susceptibility to esophageal carcinoma in China. Ninety-seven patients with newly diagnosed, untreated esophageal squamous-cell carcinoma (ESCC) and 97 healthy controls matched in age, gender, and residence were recruited in this community-based case-control study. Null genotypes of GSTM1 and GSTT1 were determined by multiplex polymerase chain reaction (PCR) technique. Ile105Val polymorphism in the fifth exon, mRNA level, CpG island hypermethylation of promoter, and protein levels of GSTP1 gene were measured with peripheral blood mononuclear cell (PBMC) by PCR–restriction fragment length polymorphism (PCR-RFLP) techniques, quantitative real-time reverse transcription PCR, methylation-specific PCR (MSP), and Western blotting, respectively. The results showed that GSTM1 null genotype and GSTT1 null genotype were significantly associated with increased risk for esophageal cancer in Chinese population. Compared with the control, the relative expression levels of mRNA were significantly reduced in ESCC patients. The conditional logistic regression analysis demonstrated that increased risk for esophageal cancer was associated with CpG island hypermethylation of promoter of GSTP1 gene. GSTP1 protein levels also showed significant decrease in ESCC when adjusted for age, gender, smoking status, and alcohol use. An individual with GSTM1 or GSTT1 null genotype may thus be more susceptible to esophageal cancer development. Reduced expression in mRNA and protein levels were the main manifestations noted in aberrant function of GSTP1 gene. Data thus suggest that the CpG island hypermethylation of promoter gene may serve as a useful biomarker for early diagnosis of esophageal carcinoma development.

Expression profiling and pathway analysis of microRNA expression in the lungs of mice exposed to long-term, low-dose benzo(a)pyrene

We investigated the effect of low-dose, long-term benzo(a)pyrene exposure on the miRNA expression profile in lung tissue of mice, and the potential mechanism of miRNAs in the benzo(a)pyreneinduced damage to health. Subject mice were treated with 5 μg/kg benzo(a)pyrene twice a week for 8 weeks by intragastrical administration, while control mice were treated with the same volume of olive oil solvent. All mice were then fed for another 8 weeks without exposure to benzo(a)pyrene, after which total RNA was isolated from lung tissue. miRNA expression profiles were generated by SOLiD™3 high-throughput sequencing and the signaling pathways represented were analyzed by DIANA-mirPath. A total of 74 miRNAs were dysregulated in mice lung tissues exposed to benzo(a)pyrene. Signaling pathways regulated by benzo(a)pyrene exposure included those involved in the environmental information process and human tumorigenesis. We conclude that low-dose, long-term benzo(a)pyrene exposure alters specific miRNA expression profiles.