Association Between Multiple Metal(loid)s Exposure and Blood Lipid Levels: Evidence from a Cross-Sectional Study of Southeastern China.

Exposure to essential and toxic metals occurs simultaneously as a mixture in real-life. However, there is no consensus regarding the effects of co-exposure to multiple metal(loid)s (designated hereafter metals) on blood lipid levels. Thus, blood concentrations of six human essential metals and five toxic metals in 720 general populations from southeastern China were simultaneously determined as a measure of exposure. In addition, quantile g-computation, Bayesian kernel machine regression, elastic net regression, and generalized linear model were used to investigate both the joint and individual effects of exposure to this metal mixture on human blood lipid levels. The significant positive joint effect of exposure to this metal mixture on serum total cholesterol (TC) levels, rather than on serum triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, Castelli risk index I, Castelli risk index II, atherogenic coefficient, and non-HDL-C levels, was found. In addition, the positive effect may be primarily driven by selenium (Se), lead (Pb), and mercury (Hg) exposure. In addition, on the effect of TC levels, the synergistic effect between Pb and Hg and the antagonistic effect between Se and Pb were identified. Our finding suggests that combined exposure to this metal mixture may affect human blood lipid levels. Therefore, reducing exposure to heavy metals, such as Pb and Hg, should be a priority for the general population. In addition, Se supplementation should also be considered with caution.

Sustained release of arsenic trioxide benefits interventional therapy on rabbit VX2 liver tumor.

The benefit of chemotherapy as a constituent of transcatheter arterial chemoembolization (TACE) is still in debate. Recently we have developed arsenic trioxide nanoparticle prodrug (ATONP) as a new anticancer drug, but its systemic toxicity is a big issue. In this preclinical TACE study, ATONP emulsified in lipiodol behaved as drug-eluting bead manner. Sustained release of arsenic from ATONP within occluded tumor caused very low arsenic level in plasma, avoiding the "rushing out" effect as ATO did. Correspondingly, intratumoral arsenic accumulation and inorganic phosphate deprivation were simultaneously observed, and arsenic concentration was much higher as ATONP was transarterially administered than ATO, or intravenously injected. Tumor necrosis and apoptosis were remarkably more severe in ATONP group than ATO, but no significant hepatic and renal toxicity was perceived. In brief, ATONP alleviated arsenic toxicity and boosted the therapeutic effect of TACE via Pi-activated drug sustainable release.

Lead exposure-induced cognitive impairment through RyR-modulating intracellular calcium signaling in aged rats.

Lead is widely distributed in the environment and has become a global public health issue. It is well known that lead exposure induces not only neurodevelopmental toxicity but also neurodegenerative diseases, with learning and memory impairment in the later stage. However, the molecular mechanisms remain elusive. The present study investigated the effects of early life and lifetime lead exposure on cognition and identified the molecular mechanisms involved in aged rats. The results herein demonstrated that the lead concentration in peripheral blood and brain tissues in aged rats was significantly increased in a lead dose-dependent manner. High-dose lead exposure caused cognitive functional impairment in aged rats, concomitant with a longer escape latency and a lower frequency of crossing the platform via Morris water maze testing compared to those in the control and low-dose lead exposure groups. Importantly, neuron functional defects were still observed even in early life lead exposure during the prenatal and weaning periods in aged rats. The neurotoxicity induced by lead exposure was morphologically evidenced by a recessed nuclear membrane, a swollen endoplasmic reticulum, and mitochondria in the neurons. Mechanistically, the exposure of aged rats to lead resulted in increasing free calcium concentration, reactive oxygen species, and apoptosis in the hippocampal neurons. Lead exposure increased RyR3 expression and decreased the levels of p-CaMKIIα/CaMKIIα and p-CREB/CREB in the hippocampus of aged rats. These findings indicated that early life lead exposure-induced cognition disorder was irreversible in aged rats. Lead-induced neurotoxicity might be related to the upregulation of RyR3 expression and high levels of intracellular free calcium with increasing lead concentration in injured neurons.

Controlled-release of antacids from biopolymer microgels under simulated gastric conditions: Impact of bead dimensions, pore size, and alginate/pectin ratio.

The highly acidic nature of the gastric fluids inside the human stomach can cause have health problems in certain individuals e.g., acid reflux and ulcers. Antacid-loaded biopolymer microgels can be used to control the acidity of the gastric fluids, which may be useful for developing functional foods to treat these problems. In this study, the impact of biopolymer microgel dimensions and composition on the dissolution rate of encapsulated antacid was determined under simulated gastric conditions. The microgels were formed by injecting antacid (magnesium hydroxide) and biopolymers (alginate or alginate/pectin) into a calcium chloride solution to promote cross-linking. Microgels of varying dimensions were formed using either a hand-held syringe or a vibrating nozzle encapsulation device with different nozzle sizes. The rate of antacid dissolution was measured using an automatic titration device (pH stat) that added HCl solution into the simulated gastric fluids to maintain a constant pH of 2.5. The antacid dissolution rate decreased with increasing microgel diameter (300 to 1660 µm) and decreasing pore size (0.8 to 2.0% alginate). The slowest dissolution rate was observed in microgels containing 80% alginate and 20% pectin, which may have been due to the impact of biopolymer composition on bead dimensions and pore size. The results of this study may be useful for the design of biopolymer microgels that can control the release of antacids in the stomach, thereby leading to better control over the pH of the gastric fluids.

Dietary, Nutrient Patterns and Blood Essential Elements in Chinese Children with ADHD.

Dietary or nutrient patterns represent the combined effects of foods or nutrients, and elucidate efficaciously the impact of diet on diseases. Because the pharmacotherapy on attention deficit hyperactivity disorder (ADHD) was reported be associated with certain side effects, and the etiology of ADHD is multifactorial, this study investigated the association of dietary and nutrient patterns with the risk of ADHD. We conducted a case-control study with 592 Chinese children including ADHD (n = 296) and non-ADHD (n = 296) aged 6-14 years old, matched by age and sex. Dietary and nutrient patterns were identified using factor analysis and a food frequency questionnaire. Blood essential elements levels were measured using atomic absorption spectrometry. A fish-white meat dietary pattern rich in shellfish, deep water fish, white meat, freshwater fish, organ meat and fungi and algae was inversely associated with ADHD (p = 0.006). Further analysis found that a mineral-protein nutrient pattern rich in zinc, protein, phosphorus, selenium, calcium and riboflavin was inversely associated with ADHD (p = 0.014). Additionally, the blood zinc was also negatively related to ADHD (p = 0.003). In conclusion, the fish-white meat dietary pattern and mineral-protein nutrient pattern may have beneficial effects on ADHD in Chinese children, and blood zinc may be helpful in distinguishing ADHD in Chinese children.

Selection of nutrients for prevention or amelioration of lead-induced learning and memory impairment in rats.

BACKGROUND: We carried out animal experiments based on the orthogonal design L(8)(2(7)) setting seven factors with two different levels of each and 10 groups of rats. The nutrients tested were tyrosine, glycine, methionine, taurine, ascorbic acid, thiamine and zinc. OBJECTIVES: The objective of this study was to explore the optimal combinations of nutrients for prevention or amelioration of lead-induced learning and memory impairment. METHODS: Rats were supplemented with nutrients by gavage once a day in two experiments: one was simultaneous nutrient supplementation with lead acetate administration (800 mg l(-1)) for 8 weeks (prophylactic supplementation) and the other was nutrient supplementation for 4 weeks after the cessation of 4 weeks of lead administration (remedial supplementation). Morris water maze was initiated at ninth week. Rats were terminated for assays of levels of Pb in blood, activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in hippocampus, levels of nitric oxide (NO) in hippocampus and expressions of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) response element-binding protein messenger RNA in hippocampus. RESULTS: Results showed that in prophylactic supplementation, methionine, taurine, zinc, ascorbic acid and glycine were the effective preventive factors for decreasing prolonged escape latency, increasing SOD and NOS activities and NO levels in the hippocampus, respectively. On the other hand, in remedial supplementation, taurine was the effective factor for reversing Pb-induced decrease in activities of SOD, NOS and levels of NO. CONCLUSIONS: In conclusion, the optimum combinations of nutrients appear to be methionine, taurine, zinc, ascorbic acid and glycine for the prevention of learning and memory impairment, while taurine and thiamine appear to be the effective factors for reversing Pb neurotoxicity.