Ameliorative effects of different doses of selenium against fluoride-triggered apoptosis and oxidative stress-mediated renal injury in rats through the activation of Nrf2/HO-1/NQO1 signaling pathway.

Excess fluoride (F) exposure can cause oxidative stress in the kidney. As an antioxidant, selenium (Se) can potentially protect the kidney from F-induced injury in rats. Hence, the histopathological, renal biochemical, oxidative stress, and apoptotic-related indices upon exposure to 100 mg/L sodium fluoride (NaF) and various doses of sodium selenite (Na2SeO3; 0.5, 1, and 2 mg/L) were assessed. Our results demonstrated that F-mediated renal structural damage and apoptosis elevated the content of serum creatinine (SCr), inhibited the activity of catalase (CAT) in serum, and increased the production of reactive oxygen species (ROS) in kidney and malondialdehyde (MDA) in serum. Interestingly, 1 mg/L dietary supplementation of Se tangibly mitigated these injuries. Furthermore, F could also change the gene and protein expression of the nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase1 (NQO1). Concomitantly, the different concentrations of Se notably alleviated their expression. Taken together, 1-2 mg/L Se ameliorated F-induced renal injury through oxidative stress and apoptosis-related routes. The recorded ameliorative effects might be related to the activation of the Nrf2/HO-1/NQO1 signaling pathway.

Sensitive electrochemical detection of enrofloxacin in eggs based on carboxylated multi-walled carbon nanotubes-reduced graphene oxide nanocomposites: Molecularlyimprintedrecognition versus direct electrocatalytic oxidation.

A sensitive electrochemical method for detecting enrofloxacin was proposed using carboxylated multi-walled carbon nanotubes-reduced graphene oxide (MWCNT-COOH-RGO) nanocomposites. The MWCNT-COOH-RGO nanocomposites were firstly electrodeposited on a bare electrode, followed by electropolymerization of molecularly imprinted polymers. Enrofloxacin was determined by the mechanisms of direct electrocatalytic oxidation and molecularly imprinted recognition, respectively. Under the optimized conditions, a response range of 5.0×10-7 M to 5.5×10-5 M and limit of detection (LOD) of 2.3×10-7 M were obtained by direct electrocatalytic oxidation of enrofloxacin using chronoamperometry. By contrast, the response range of 1.0×10-10 M to 5.0×10-5 M and LOD of 2.5×10-11 M were achieved by molecularly imprinted recognition of enrofloxacin using square-wave voltammetry. Moreover, the proposed method exhibited good repeatability, stability and selectivity, and could be used for enrofloxacin detection in egg samples with satisfactory results.

Synthesis of Fluorescent Carbon Dots and Their Application in Ascorbic Acid Detection.

Water-soluble fluorescent carbon dots (CDs) were synthesized by a hydrothermal method using citric acid as the carbon source and ethylenediamine as the nitrogen source. The repeated and scale-up synthetic experiments were carried out to explore the feasibility of macroscopic preparation of CDs. The CDs/Fe3+ composite was prepared by the interaction of the CDs solution and Fe3+ solution. The optical properties, pH dependence and stability behavior of CDs or the CDs/Fe3+ composite were studied by ultraviolet spectroscopy and fluorescence spectroscopy. Following the principles of fluorescence quenching after the addition of Fe3+ and then the fluorescence recovery after the addition of asorbic acid, the fluorescence intensity of the carbon dots was measured at λex = 360 nm, λem = 460 nm. The content of ascorbic acid was calculated by quantitative analysis of the changing fluorescence intensity. The CDs/Fe3+ composite was applied to the determination of different active molecules, and it was found that the composite had specific recognition of ascorbic acid and showed an excellent linear relationship in 5.0-350.0 µmol·L-1. Moreover, the detection limit was 3.11 µmol·L-1. Satisfactory results were achieved when the method was applied to the ascorbic acid determination in jujube fruit. The fluorescent carbon dots composites prepared in this study may have broad application prospects in a rapid, sensitive and trace determination of ascorbic acid content during food processing.

Preparation of biocompatible nano-ZnO/chitosan microspheres with multi-functions of antibacterial, UV-shielding and dye photodegradation.

Nano-ZnO (nZnO) has been widely used as antibacterial, UV-shielding and photocatalysis materials, but limited by its contentious biosafety. In this paper, chitosan (CS) was introduced to enhance the biocompatibility. To solve the problem that nZnO reacts with the CS acid solution, alternate-feed spray drying was adopted to fabricate nZnO/CS composite microspheres. It was showed that nZnO remained the hexagonal phase, dispersed and embedded into CS microspheres. Based on the results of cytotoxicity and hemolysis test, biosafety was improved obviously. Further, the antibacterial activity of nZnO/CS was notably better than either of CS and nZnO individually. UV-shielding property and photocatalytic degradation test were estimated. In a word, alternate-feed spray drying presents a novel and cost-efficient method to fabricate multifunctional nZnO/CS microspheres with enhanced biosafety.

Selenium attenuates apoptosis and p-AMPK expressions in fluoride-induced NRK-52E cells.

Fluoride is widely distributed in the environment, and excessive fluoride intake can induce cytotoxicity, DNA damage, and cell cycle changes in many tissues and organs, including the kidney. Accumulating evidence demonstrates that selenium (Se) administration ameliorates sodium fluoride (NaF)-induced kidney damage. However, the potentially beneficial effects of Se against NaF-induced cytotoxicity of the kidney and the underlying molecular mechanisms of this protection are not fully understood. At present, in this study, the normal rat kidney cell (NRK-52E) was used to investigate the potentially protective mechanism of Se against NaF-induced apoptosis, by using the methods of pathology, colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blot. The experiment was designed with a control group, two NaF-treated groups (NaF, 5, 20 mg/L), two sodium selenite-treated groups (Na2SeO3, 17.1, 34.2 µg/L), and four Se + NaF-treated groups (Na2SeO3, 17.1, 34.2 µg/L; NaF, 5, 20 mg/L). The results indicate that selenium can attenuate apoptosis and AMPK phosphorylation in the NRK-52E cell induced with fluoride. These results imply that selenium is capable to modulate fluoride-induced NRK-52E cell apoptosis via regulating the expression levels of the proteins involved in mitochondrial pathway and changes in p-AMPK expressions may also be a key process in preventing fluorosis.

Prevalence of Cigarette Smoking and Nicotine Dependence in Men and Women Residing in Two Provinces in China.

AIMS: Although it is known that there is a high smoking prevalence among Chinese, key issues such as social and environmental factors impacting smoking initiation and persistence, the percentage of smokers considered nicotine dependence (ND), and the availability and use of ND treatments have rarely been investigated. METHODS: To address these issues, from 2012 to 2014, we conducted a large-scale study in the Zhejiang and Shanxi provinces of China using the Fagerström Test for Nicotine Dependence and other validated questionnaires. RESULTS: Of the 17,057 subjects, consisting of 13,476 males and 3,581 females aged 15 years or older, the prevalence of male smoking was 66.1% [95% confidence interval (CI) 65.5%, 66.9%] and that of female smoking was 3.2% (95% CI 3.0%, 3.8%). Among males, 25.8% (95% CI 25.0%, 26.5%) were low-to-moderate ND, and 11.8% (95% CI 11.2%, 12.3%) were high ND (H-ND), persons who have significant difficulty quitting without treatment. The degrees of ND were related to age, extent of education, and annual family income. The social-environmental factors examined conveyed a higher risk for smoking initiation, which is particularly true for the influence of smoking by friends. Furthermore, current smokers had a significantly higher risk of suffering respiratory and digestive symptoms. CONCLUSION: These data not only show a high smoking prevalence in Chinese men but also reveal that a relatively large number of smokers are H-ND. Considering that few Chinese smokers seek ND treatment, a comprehensive smoking prevention and treatment program designed specifically for Chinese is greatly needed.

Role of IL-17 Pathways in Immune Privilege: A RNA Deep Sequencing Analysis of the Mice Testis Exposure to Fluoride.

We sequenced RNA transcripts from the testicles of healthy male mice, divided into a control group with distilled water and two experimental groups with 50 and 100 mg/l NaF in drinking water for 56 days. Bowtie/Tophat were used to align 50-bp paired-end reads into transcripts, Cufflinks to measure the relative abundance of each transcript and IPA to analyze RNA-Sequencing data. In the 100 mg/l NaF-treated group, four pathways related to IL-17, TGF-ß and other cellular growth factor pathways were overexpressed. The mRNA expression of IL-17RA, IL-17RC, MAP2K1, MAP2K2, MAP2K3 and MAPKAPK2, monitored by qRT-PCR, increased remarkably in the 100 mg/L NaF group and coincided with the result of RNA-Sequencing. Fluoride exposure could disrupt spermatogenesis and testicles in male mice by influencing many signaling pathways and genes, which work on the immune signal transduction and cellular metabolism. The high expression of the IL-17 signal pathway was a response to the invasion of the testicular immune system due to extracellular fluoride. The PI3-kinase/AKT, MAPKs and the cytokines in TGF-ß family were contributed to control the IL-17 pathway activation and maintain the immune privilege and spermatogenesis. All the findings provided new ideas for further molecular researches of fluorosis on the reproduction and immune response mechanism.

Prevalence and dissemination of antibiotic resistance genes and coselection of heavy metals in Chinese dairy farms.

This study aims to explore prevalence and dissemination of antibiotic resistance genes (ARGs) in dairy farms. A variety of ARGs conferring resistance to most classes of antibiotics were detected in feces and soil samples obtained from dairy farms, using a high-throughput metagenomic sequencing approach. The ARGs observed in the feces and the soil samples were significantly correlated (p<0.01). The abundance of mobile genetics elements, such as transposase, was also examined to evaluate the potential risk of horizontal ARGs transfer. The positive correlation (p<0.001) between the total abundance of transposase genes and ARGs in the soil samples suggested strong dissemination capacity of ARGs in soil. In addition, the ARGs and metal resistance genes (MRGs) were significantly correlated with heavy metals in the feces (p<0.01), suggesting that the heavy metals promoted the emergence of metal resistance, and participated in the coselection processes for ARGs. The prevalence of ARGs with high levels of genetic mobile elements in the dairy farms suggests that cattle excrement is a major reservoir of ARGs with a high risk of dissemination, which increases the potential risk of environmental pollution and threatens public health.

Regulation of LPS-induced mRNA expression of pro-inflammatory cytokines via alteration of NF-κB activity in mouse peritoneal macrophages exposed to fluoride.

F toxicity to immune system, especially to macrophage, has been studied a lot recently. Nuclear factor-kappa B (NF-κB), as a transcription factor, plays a central role in immune and inflammatory responses via the regulation of downstream gene expression. Recent studies indicated that fluoride effect on inflammatory cytokine secretion, however, the molecular mechanism was less understood. In our study, peritoneal macrophages (PMs) were divided several groups and were administrated sodium fluoride (NaF, 50, 100, 200, 400, 800 µM) and/or lipopolysaccharide (LPS, 30 ng/mg). The mRNA expression of p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) in macrophages exposed to fluoride was determined by quantitative real-time RT-PCR respectively. The translocation of NF-κB from cytoplasm to nucleus, which in a way reflects NF-κB activity, was demonstrated by Immunofluorescence and ELISA. Our results showed that fluoride had a dose-dependent effect on NF-κB activity, which coincided with LPS-induced mRNA expression of its downstream genes, iNOS and IL-1ß. Fluoride alone causes no effect on gene expression. However, the mRNA expression of TNF-α showed non-NF-κB-dependent manner. Therefore, we come to the conclusion that fluoride can regulate LPS-induced mRNA expression of iNOS and IL-1ß via NF-κB pathway in mouse peritoneal macrophages.

In vitro investigation on the magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate for breast cancer treatment.

Cancer comprehensive treatment has been fully recognized as it can provide an effective multimodality approach for fighting cancers. In therapeutic oncology, hyperthermic adjuvant chemotherapy termed as thermochemotherapy plays an increasing role in multimodality cancer treatment. Currently, targeted nanothermotherapy is one of the effective hyperthermia approach based on magnetic nanoparticles (MNPs), which can be achieved by applying biocompatible nanoscaled metallic particles that convert electromagnetic energy into heat, for instance, magnetic fluid hyperthermia (MFH) mediated by superparamagnetic iron oxide nanoparticles (SPIONs). Upon exposure under alternative magnetic field (AMF), SPIONs can generate heat through oscillation of their magnetic moment. Nowadays, clinical trials at phase II are now under investigations for MFH on patients in Germany and Japan and demonstrate very inspiring for cancer therapy. In this work we explore the feasibility and effectiveness of magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate, an anti-cancer drug, for breast cancer comprehensive treatment. Amino silane coated MNPs as agent of MFH were prepared by the chemical precipitation method. Physiochemical characterizations on MNPs have been systematically carried out by various instrumental analyses. Inductive heating property of the MNPs was evaluated by monitoring the temperature increase of the MNPs suspension under AMF. The in-vitro cytotoxicity results on human breast cancer cell MCF-7 by CCK-8 assay indicated the bi-modal cancer treatment approach for combined MFH and chemotherapy is more effective than mono-modal treatment, indicating a thermal enhancement effect of hyperthermia on drug cytocoxicity. The magnetic thermochemotherapy mediated by MNPs combined with methotrexate can realize cancer comprehensive treatment thus has great potential in clinical application.