Long Xu

Elevated lead levels and adverse effects on natural killer cells in children from an electronic waste recycling area.

Lead (Pb) has been proved to exert immunotoxicity to influence immune homeostasis in humans. To monitor the internal Pb level and evaluate its effect on natural killer (NK) cells and cytokine/chemokine concentrations, we recruited 285 preschool children from Guiyu, one of the largest electronic waste (e-waste) destinations and recycling areas in the world, and known to have high concentrations of Pb in the air, soil, water, sediment and plants. A total of 126 preschool children were selected from Haojiang as a reference group. Results showed that children in Guiyu, the exposed area, had higher blood Pb levels and lower percentages of NK cells than children from the reference area. A significantly negative association was found between the percentage of NK cells and increasing Pb levels. Moreover, children in Guiyu area had higher platelet counts and IL-1β concentrations, and lower levels of IL-2, IL-27, MIP-1α and MIP-1β were observed in the exposed children. These changes might not be conducive to the development and differentiation of NK cells. Taken together, the elevated Pb levels result in the lower percentages of NK cells, but also alter the levels of platelets, IL-1β and IL-27, which might be unconducive to the activity and function of NK cells.

Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p<0.01), shorter body length and higher gestational age (p<0.01). After bivariate adjustment in a linear regression model, decreases of 205.05g in weight and 0.44cm in body length were associated with a 10ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd.

Hearing loss in children with e-waste lead and cadmium exposure

Environmental chemical exposure can cause neurotoxicity and has been recently linked to hearing loss in general population, but data are limited in early life exposure to lead (Pb) and cadmium (Cd) especially for children. We aimed to evaluate the association of their exposure with pediatric hearing ability. Blood Pb and urinary Cd were collected form 234 preschool children in 3-7years of age from an electronic waste (e-waste) recycling area and a reference area matched in Shantou of southern China. Pure-tone air conduction (PTA) was used to test child hearing thresholds at frequencies of 0.25, 0.5, 1, 2, 4 and 8kHz. A PTA≥25dB was defined as hearing loss. A higher median blood Pb level was found in the exposed group (4.94±0.20 vs 3.85±1.81μg/dL, p<0.001), while no significance was found for creatinine-adjusted Cd. Compared with the reference group, the exposed group had a higher prevalence of hearing loss (28.8% vs 13.6%, p<0.001). The PTA in the left, right and both ears, and hearing thresholds at average low and high frequency, and single frequency of 0.5, 1 and 2kHz were all increased in the exposed group. Positive correlations of child age and nail biting habit with Pb, and negative correlations of parent education level and child washing hands before dinner with Pb and Cd exposure were observed. Logistic regression analyses showed the adjusted OR of hearing loss for Pb exposure was 1.24 (95% CI: 1.029, 1.486). Our data suggest that early childhood exposure to Pb may be an important risk factor for hearing loss, and the developmental auditory system might be affected in e-waste polluted areas.

Elevated biomarkers of sympatho-adrenomedullary activity linked to e-waste air pollutant exposure in preschool children

Air pollution is a risk factor for cardiovascular disease (CVD), and cardiovascular regulatory changes in childhood contribute to the development and progression of cardiovascular events at older ages. The aim of the study was to investigate the effect of air pollutant exposure on the child sympatho-adrenomedullary (SAM) system, which plays a vital role in regulating and controlling the cardiovascular system. Two plasma biomarkers (plasma epinephrine and norepinephrine) of SAM activity and heart rate were measured in preschool children (n = 228) living in Guiyu, and native (n = 104) and non-native children (n = 91) living in a reference area (Haojiang) for >1 year. Air pollution data, over the 4-months before the health examination, was also collected. Environmental PM2.5, PM10, SO2, NO2 and CO, plasma norepinephrine and heart rate of the e-waste recycling area were significantly higher than for the non-e-waste recycling area. However, there was no difference in plasma norepinephrine and heart rate between native children living in the non-e-waste recycling area and non-native children living in the non-e-waste recycling area. PM2.5, PM10, SO2 and NO2 data, over the 30-day and the 4-month average of pollution before the health examination, showed a positive association with plasma norepinephrine level. PM2.5, PM10, SO2, NO2 and CO concentrations, over the 24 h of the day of the health examination, the 3 previous 24-hour periods before the health examination, and the 24 h after the health examination, were related to increase in heart rate. At the same time, plasma norepinephrine and heart rate on children in the high air pollution level group (≤50-m radius of family-run workshops) were higher than those in the low air pollution level group. Our results suggest that air pollution exposure in e-waste recycling areas could result in an increase in heart rate and plasma norepinephrine, implying e-waste air pollutant exposure impairs the SAM system in children.

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Background/Aims: Renal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS), and nitroso-redox imbalance. The calcium-sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM). Methods: The bilateral renal arteries and veins of streptozotocin (STZ)-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR) and NPS-2143 (antagonist of CaSR) at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM), and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE) staining, transmission electron microscope (TEM), commercial kits, enzyme-linked immunosorbent assay (ELISA), and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer

Background Lumbrokinase (LK) is an enzyme complex with antithrombotic, antioxidant, antitumor, and immunomodulatory effects. It has been extensively studied and used in clinical anti-tumor therapy. However, its half-life is short, its bioavailability is low, and its toxicity and side effects are great, which greatly limit its clinical application. Therefore, LK is often combined with other drugs (such as immune agents, hormones, or Chinese herbal medicine) to reduce its dosage and side effects and to improve its anti-tumor effects. Methods and results Here, we described an LK/paclitaxel (PTX) nanocarrier based on poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyoxycarbonyl-l-lysine)-r-poly(l-lysine)) (PEG-b-(PELG-g-(PZLL-r-PLL))). In the present study, LK and PTX were loaded by electrostatic and/or hydrophobic effects under mild conditions, thereby increasing the half-life and bioavailability of the drugs via the sustained release and enhancement of tumor site enrichment by the LK/PTX/PEG-b-(PELG-g-(PZLL-r-PLL)) complex through passive targeting. In this study, using bladder cancer cells (J82 cells) and rat bladder cancer model as the object, the structure of the nanocarrier, the relationship between drugs composition and antitumor properties were systematically studied. Conclusion We propose that the block copolymer PEG-b-(PELG-g-(PZLL-r-PLL)) may function as a potent nanocarrier for augmenting anti-bladder cancer pharmacotherapy, with unprecedented clinical benefits.

Interactions between polycyclic aromatic hydrocarbons and epoxide hydrolase 1 play roles in asthma

Asthma, as one of the most common chronic diseases in children and adults, is a consequence of complex gene–environment interactions. Polycyclic aromatic hydrocarbons (PAHs), as a group of widespread environmental organic pollutants, are involved in the development, triggering and pathologic changes of asthma. Various previous studies reported the critical roles of PAHs in immune changes, oxidative stress and environment–gene interactions of asthma. EPHX1 (the gene of epoxide hydrolase 1, an enzyme mediating human PAH metabolism) had a possible association with asthma by influencing PAH metabolism. This review summarized that (1) the roles of PAHs in asthma—work as risk factors; (2) the possible mechanisms involved in PAH-related asthma—through immunologic and oxidative stress changes; (3) the interactions between PAHs and EPHX1 involved in asthma—enzymatic activity of epoxide hydrolase 1, which affected by EPHX1 genotypes/SNPs/diplotypes, could influence human PAH metabolism and people’s vulnerability to PAH exposure. This review provided a better understanding of the above interactions and underlying mechanisms for asthma which help to raise public’s concern on PAH control and develop strategies for individual asthma primary prevention.

Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

Background/Aims: Paeoniflorin (PF) is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund’s complete adjuvant (CFA)-induced inflammatory pain and explore the underlying molecular mechanism. Methods: An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1β and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot. Results: PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro. Conclusion: These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.