Environmentally Persistent Free Radical Promotes Lung Cancer Progression by Regulating the Expression Profile of miRNAs.

Background: Environmentally persistent free radicals (EPFRs) are generated in the combustion processes of solid waste and can cause adverse influences on human health, especially lung diseases. Lung cancer is one of the most serious malignancies in recent years, which the global deaths rate is about 1.6 million every year. Methods and Results: In this study, we verified that ZnO/MCB EPFRs promote cell proliferation and migration, impedes cell apoptosis in lung cancer. Furthermore, we found that ZnO/MCB could influence the expression of miRNAs (miR-18a and miR-34a). In vivo, ZnO/MCB and ZnO EPFRs can reduce the weight and survival rate of BALB/c male mice more than that of BALB/c female mice. In the ZnO/MCB exposed group, male mice lung became even smaller, while the female mice the lung increased significantly. Taken together, our results provide evidence for assessing the potential health risks of persistent free radicals on fine particles. Conclusions: This study linked toxicity of EPFRs with miRNAs revealed the potential health hazard to human lung cancer.

Facile Synthesis of CeO2-LaFeO3 Perovskite Composite and Its Application for 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK) Degradation.

A facile and environmentally friendly surface-ion adsorption method using CeCO3OH@C as template was demonstrated to synthesize CeO2-LaFeO3 perovskite composite material. The obtained composite was characterized by X-ray diffraction (XRD), fourier transform infrared spectra (FT-IR), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), thermo-gravimetric analysis and differential scanning calorimetry (TG-DSC), N2 adsorption/desorption isotherms and X-ray photoelectron spectra (XPS) measurements. The catalytic degradation of nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was tested to evaluate catalytic activity of the CeO2-LaFeO3 composite. Much better activity was observed for the CeO2-LaFeO3 composite comparing with CeO2 and LaFeO3. These results suggested that perovskite composite materials are a promising candidate for the degradation of tobacco-specific nitrosamines (TSNAs).

A new prenylated indole diketopiperazine alkaloid from Eurotium cristatum.

A new prenylated indole diketopiperazine alkaloid, cristatumin F (1), and four known metabolites, echinulin (2), dehydroechinulin (3), neoechinulin A (4) and variecolorin O (5), were isolated from the crude extract of the fungus Eurotium cristatum. The structure of 1 was elucidated primarily by NMR and MS methods. The absolute configuration of 1 was assigned using Marfey's method applied to its acid hydrolyzate. Cristatumin F (1) showed modest radical scavenging activity against DPPH radicals, and exhibited marginal attenuation of 3T3L1 pre-adipocytes.

Preparation of phenyl group-functionalized magnetic mesoporous silica microspheres for fast extraction and analysis of acetaldehyde in mainstream cigarette smoke by gas chromatography-mass spectrometry.

Acetaldehyde is regarded as a toxic mainstream cigarette smoke constituent, and measurement of acetaldehyde in complex real samples is difficult owing to its high volatility and reactivity. In this work, phenyl group-functionalized magnetic mesoporous microspheres were developed as the solid-phase extraction sorbents for enrichment and analysis of acetaldehyde in mainstream cigarette smoke. The functional magnetic microspheres were first synthesized through a facile one-pot co-condensation approach. The prepared nanomaterials possessed abundant silanol groups in the exterior surface and numerous phenyl groups in the interior pore-walls, as well as a large surface area (273.5m(2)/g), strong superparamagnetism and uniform mesopores (3.3 nm). Acetaldehyde in mainstream cigarette smoke was collected in water and derivatizated with O-2,3,4,5,6-(pentafluorobenzyl)hydroxylamine. The formed acetaldehyde oximes were extracted and enriched by the prepared adsorbents via π-π interactions and subsequently analyzed using GC-MS. Extraction conditions such as amounts of sorbents, eluting solvent, adsorption and desorption time were investigated and optimized to achieve the best efficiency. Method validations including linearity, recovery, repeatability, and limit of detection were also studied. It was found that the suggested methodology provided low detection limit of 0.04 mg/mL, good recovery of 88-92%, intra-day and inter-day RSD values of 4.5% and 10.1%, and linear range of 0.25-4 mg/mL (R(2)=0.999). The results indicated that the proposed method based on phenyl-functionalized magnetic mesoporous microspheres was rapid, efficient and convenient for the enrichment and analysis of acetaldehyde in tobacco.

Development of a rapid method for the simultaneous separation and determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its N- and O-glucuronides in human urine by liquid chromatography-tandem mass spectrometry.

Determination of the tobacco-specific nitrosamine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its N- and O-glucuronides (NNAL-N-Gluc and NNAL-O-Gluc) is important for toxicology analysis of tobacco smoke induced carcinogenicity and the understanding of detoxification mechanisms of the carcinogenic nitrosamine in humans. But previously reported indirect measurement methods involving enzymolysis and base treatment steps were tedious and time-consuming. In this work, a direct measurement method for simultaneous determination of urinary NNAL, NNAL-N-Gluc and NNAL-O-Gluc by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a single run was developed for the first time without the need to perform enzymatic or base hydrolysis. Urine samples were purified using dichloromethane and further extracted by solid-phase extraction. Then they were analyzed by LC-MS/MS operated in electrospray positive ionization mode. Chromatographic separation was achieved on a Phenomenex Kinetex PFP column within 6 min. The proposed method was validated and the results demonstrated that the method can produce satisfactory recoveries and reproducibility for the analytes. The applicability of this newly developed method was investigated for the simultaneous analysis of the three metabolites in smokers' urine and the obtained results were comparable to those detected using the conventional enzymolysis method.

Preparation and characterization of organic-functionalized mesoporous silica as heavy metal adsorbents.

Novel organic-inorganic hybrid mesoporous materials have attracted much attention because the functional organic groups can bring these materials special properties, such as selective absorption and new catalytic properties. In this paper, two kind of bis(triethoxysilyl) organic skeleton (EtO)3Si-(CH2)3-NH-C(O)-X-C(O)-NH-(CH2)3-Si(OEt)3 (X = 1,4-benzene (BSPB), 2,5-thienyl (BSPT)) precursors were synthesized firstly. Then bridged organic-inorganic hybrid mesoporous materials were prepared by direct grafting on MCM-41. The MCM-41 was obtained under basic conditions using cetyltrimethylammonium bromide (CTAB) as a template with tetraethyl orthosilicate. FT-IR spectra showed the acylamino, carbonyl, phenyl and thienyl groups had been introduced into the materials. The structures of these materials were further confirmed by X-ray diffraction (XRD) and the N2 adsorption-desorption. In addition, the adsorption capacity of heavy metal ions such as mercury, cadmium, and lead, was evaluated. The results indicated that the functionalized mesoporous materials with high porosity and specific surface area were successfully prepared, and the new prepared materials exhibited good adsorption capacity for heavy metal ions Hg2+, Cd2+, and Pb2+.

Surface properties of solid materials measured by modified inverse gas chromatography.

A novel modified inverse gas chromatography (IGC) method has been developed to investigate the surface properties of solid materials. On the modified IGC system, the every adjusted retention time of miscellaneous probe molecules can be rapidly calculated within only one sample injection through wisely induction a capillary column and two detectors, i.e., flame ionization detector (FID) and thermal conductivity detector (TCD). In the system, the relative dead time can be acquired from FID detector while the retention time can be obtained from TCD detector simultaneously. The significant advantage of our design is that, experimental time is greatly saved compared to the traditional IGC. In addition, the new system is capable of distinguishing variety surface properties of porous materials. Two types of active carbon samples were tested, and the results showed that their thermodynamic parameters were quite different, indicating that the samples have opposite acidic/basic properties. The use of IGC would be an effective tool to evaluate the physiochemical data of solid materials.

Development, validation, and application of a liquid chromatography-tandem mass spectrometry method for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in human hair.

The tobacco-specific nitrosamine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a valuable biomarker for human exposure to the carcinogenic nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in tobacco and tobacco smoke. In this work, an efficient and sensitive method for the analysis of NNAL in human hair was developed and validated. The hair sample was extracted by NaOH solution digestion, purified by C(18) solid-phase extraction (SPE) and molecularly imprinted solid-phase extraction, further enriched by reverse-phase ultrasound-assisted dispersive liquid-liquid microextraction (USA-DLLME) into 1.0 % aqueous formic acid, and finally analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry. Good linearity was obtained in the range of 0.24-10.0 pg/mg hair with a correlation coefficient of 0.9982, when 150 mg hair was analyzed. The limit of detection and lower limit of quantification were 0.08 and 0.24 pg/mg hair, respectively. Accuracies determined from hair samples spiked with three different levels of NNAL ranged between 87.3 and 107.7 %. Intra- and inter-day relative standard deviations varied from 4.1 to 8.5 % and from 6.9 to 11.3 %, respectively. Under the optimized conditions, an enrichment factor of 20 was obtained. Finally, the developed method was applied for the analysis of NNAL in smokers' hair. The proposed sample preparation procedure combining selectivity of two-step SPE and enrichment of DLLME significantly improves the purification and enrichment of the analyte and should be useful to analyze NNAL in hair samples for cancer risk evaluation and cancer prevention in relation to exposure to the tobacco-specific carcinogen NNK.

The application of hepatic P450 reductase null gpt delta mice in studying the role of hepatic P450 in genotoxic carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mutagenesis.

The cytochrome P450 (P450 or CYP) is involved in both detoxification and metabolic activation of many carcinogens. In order to identify the role of hepatic P450 in the mutagenesis of genotoxic carcinogens, we generated a novel hepatic P450 reductase null (HRN) gpt delta mouse model, which lacks functional hepatic P450 on a gpt delta mouse background. In this study, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was used to treat HRN gpt delta mice and control littermates. Gene mutations in the liver and lungs were detected, and mutation spectra were analyzed. Pharmacokinetic analyses were performed, and tissue levels of NNK and metabolite were determined. NNK-induced mutant frequencies (MFs) were equivalent to spontaneous MFs in the liver, but increased more than 3 times in the lungs of HRN gpt delta mice compared to control mice. NNK-induced mutation spectra showed no difference between HRN gpt delta mice and control littermates. Toxicokinetic studies revealed reduced clearance of NNK with elevated tissue concentrations in HRN gpt delta mice. To our knowledge, these are the first data demonstrating that NNK cannot induce mutagenesis in the liver without P450 metabolic activation, but can induce mutagenesis in lungs by a hepatic P450-independent mechanism. Moreover, our data show that hepatic P450 plays a major role in the systemic clearance of NNK, thereby protecting the lungs against NNK-induced mutagenesis. Our model will be useful in establishing the role of hepatic versus extrahepatic P450-mediated mutagenesis, and the relative contributions of P450 compared to other biotransformation enzymes in the genotoxic carcinogens' activation.