ABSTRACT
Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) mediated by nanozymes has been extensively studied both experimentally and theoretically, but the low catalytic efficiency due to insufficient H2O2 in the TME and the poor biodegradability of the nanozymes are still main challenges for clinical translation of nanozymes. Herein, we designed a H2O2 self-supplying nanozyme bearing glucose oxidase (GOX) and polyethyleneimine based on a degradable iron-doped phosphate-based glass (FePBG) nanomimic (FePBG@GOX), which can convert endogenous glucose into toxic hydroxyl radicals. The GOX loaded on the nanozyme can effectively consume glucose in tumor cells to produce a large amount of H2O2 to make up for the lack of H2O2 in the TME. Thereafter, enormous hydroxyl radicals, based on a Fenton reaction of FePBG without any exogenous H2O2, are generated to induce severe apoptosis of tumor cells. The nanozyme exhibits enhanced in vitro cytotoxicity in a high-glucose medium than in a low-glucose medium, illustrating sufficient generation of H2O2 by GOX. The excellent in vivo antitumor efficacy is manifested by a high tumor growth inhibition ratio of 94.65% in model mice. Excellent intrinsic biodegradability owing to its phosphate-based glass nature is a remarkable advantage of the prepared FePBG nanozyme over most other reported nanozymes. Big concerns about side effects caused by long-time residence in living organisms are eliminated since it degrades not only in an acid medium but also in a neutral physiological environment. Therefore, this novel strategy of the TME-responsive H2O2 self-supplying nanozyme based on an endogenous cascade catalytic reaction opens up an avenue for designing degradable nanozymes in CDT.
Subject(s)
Hydrogen Peroxide , Neoplasms , Animals , Cell Line, Tumor , Glucose , Glucose Oxidase/metabolism , Hydrogen Peroxide/metabolism , Hydroxyl Radical , Iron , Mice , Neoplasms/drug therapy , Phosphates , Tumor MicroenvironmentABSTRACT
Exposure to organochlorine pesticides (OCPs) can cause adverse health effects in the female population. We investigated the dietary OCP intake of childbearing-age women living in large agricultural areas of Northern China, as well as their associated health risks. Ten childbearing-age women were recruited during 2015-2016. Their weekly dietary intake diaries and food samples were collected over the course of five visits. The OCP residues of 322 food samples from seven categories (i.e., cereal, vegetable, fruit, fish, meat, egg, and milk) were analyzed by gas chromatography-mass spectrometry. The average concentrations of the total hexachlorocyclohexanes (ΣHCH), dichlorodiphenyltrichloroethanes and their metabolites (ΣDDX), endosulfans (ΣES), and dieldrin and endrin (ΣDrin) in all food categories were, overall, much lower than the maximum residue limits. Relative high mean residues of ΣDrin and ΣES were found in fruits (ΣDrin: 0.687 ng g-1 wet weight (w.w.), ΣES: 2.24 ng g-1 w.w.) and vegetables (ΣDrin: 0.690 ng g-1 w.w., ΣES: 2.11 ng g-1 w.w.). The estimated daily dietary intake (EDI) of these compounds was calculated, with mean levels of 10.6 (ΣES) > 4.37 (ΣDrin) > 1.51 (ΣHCH) > 0.850 (ΣDDX) ng kg-1 day-1. Women during the heating period (from January to March) tended to ingest more ΣHCH, ΣDDX, ΣDrin, and ΣES. Overall, women had no obvious non-carcinogenic and carcinogenic risks due to intake of OCPs, but 83.9% of them has potential carcinogenic risk, with estimated life carcinogenic risk (LCR) exceeding 10-6. Furthermore, women had a higher potential carcinogenic risk during the heating period (mean LCR: 1.33 × 10-5) than during the non-heating period (mean LCR: 8.50 × 10-6). ΣDrin was the dominant OCP responsible for health risks, followed by ΣHCH. We concluded that women in North China still have some dietary OCP intake, especially during the heating period.
ABSTRACT
The relationship between excess copper (Cu) intake and lipid metabolic disorders is not well-studied, and most studies on this topic have a cross-sectional design. Here, we investigated the relationship between Cu exposure and blood lipid metabolism in women population, as well as potential mediation effects of oxidative stress and inflammation, using a repeated-measurement study. A total of 35 women in northern China were included, and each individual was visited for five times. Blood samples were collected, and the following serum biomarkers were analyzed: heme oxygenase-1 (HO-1), monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-6, IL-8, and lipids [triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and lipoprotein(a) (Lp(a))]. A linear mixed-effect model was used to analyze the associations between Cu and the individual biomarkers in serum. The results showed that Cu was positively associated with TG (ß = 0.0007, P = 0.01), TC (ß = 0.0006, P = 0.002), LDL (ß = 0.0004, P ≤ 0.001), and Lp(a) (ß = 0.0004, P = 0.01), but not associated with HDL (ß = 0.0001, P = 0.19). Likewise, serum Cu was positively associated with HO-1 (ß = 0.0004, P = 0.03) and negatively associated with MCP-1 (ß = -0.0006, P = 0.003) and IL-8 (ß = -0.002, P = 0.03). Among the biomarkers of oxidative stress, inflammation, and lipids in serum, only IL-8 was negatively associated with HDL (ß = -0.0004, P = 0.009). No other associations were observed. We conclude that high Cu exposure may elevate blood lipid levels as well as disturb processes related to oxidative stress and inflammation responses.
Subject(s)
Copper , Lipid Metabolism , China , Cholesterol, HDL , Cross-Sectional Studies , Female , HumansABSTRACT
The effects of ambient fine particulate matter (PM2.5) exposure on blood pressure have been widely reported. However, there remains uncertainty regarding the underlying roles of particulate matter components. We aimed to investigate the association between ambient PM2.5 exposure and blood pressure, as well as the potential effects of trace metal(loid)s, in a repeated-measurement study that enrolled women of childbearing age. Our study included 35 participants from Hebei Province, China, each of whom was visited for five times. During each visit, we conducted questionnaire surveys, measured blood pressure, and collected blood. The daily PM2.5 exposure of participants was estimated according to their residential addresses using a spatiotemporal model that combined monitoring data with satellite measurements and chemical-transport model simulations. This model was used to calculate average PM2.5 concentrations in 1, 3, 7, 15, 30, and 60 days prior to each visit. Serum concentrations of various trace metal(loid)s were measured. A linear mixed-effects model was used to investigate associations among study variables. Overall, the mean (standard deviation) 60 days PM2.5 concentration over all five visits was 108.1(43.3) µg/m3. PM2.5 concentration was positively associated with both systolic and diastolic blood pressures. Likewise, ambient PM2.5 concentration was positively associated with serum concentrations of manganese and arsenic, and negatively associated with serum concentrations of nickel, tin, and chromium. Only the serum concentration of molybdenum was negatively associated with systolic blood pressure. We concluded that ambient PM2.5 exposure may contribute to elevated blood pressure, potentially by interfering with internal intake of various metal(loid)s in the human body.
Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , Blood Pressure , China , Environmental Exposure , Female , Humans , Metals , Particulate Matter/analysisABSTRACT
Polycyclic aromatic hydrocarbons (PAHs), nicotine, cotinine, and metals in human hair have been used as important environmental exposure markers. We aimed to develop a simple method to simultaneously analyze these pollutants using a small quantity of hair. The digestion performances of tetramethylammonium hydroxide (TMAH) and sodium hydroxide (NaOH) for human hair were compared. Various solvents or their mixtures including n-hexane (HEX), dichloromethane (DCM) and trichloromethane (TCM), HEX:DCM32 (3/2) and HEX:TCM73 (7/3) were adopted to extract organics. The recoveries of metals were determined under an optimal operation of digestion and extraction. Our results showed that TMAH performed well in dissolving human hair and even better than NaOH. Overall, the recoveries for five solutions were acceptable for PAHs, nicotine in the range of 80%-110%. Except for HEX, other four extraction solutions had acceptable extraction efficiency for cotinine from HEX:TCM73 (88 ± 4.1%) to HEX:DCM32 (100 ± 2.8%). HEX:DCM32 was chosen as the optimal solvent in consideration of its extraction efficiency and lower density than water. The recoveries of 12 typical major or trace metals were mainly in the range of 90%-110% and some of them were close to 100%. In conclusion, the simultaneous analysis of PAHs, nicotine, cotinine, and metals was feasible. Our study provided a simple and low-cost technique for environmental epidemiological studies.