Blood lead levels of children exposed to e-waste: a systematic review and meta-analysis.

Blood lead levels (BLLs) have been decreasing worldwide for decades. However, systematic reviews and quantitative syntheses of BLLs in electronic waste (e-waste)-exposed children are lacking. To summarize temporal trend of BLLs among children in e-waste-recycling areas. Fifty-one studies met the inclusion criteria and included participants from six countries. Meta-analysis was performed using the random-effects model. Results showed that among e-waste-exposed children, the total geometric mean (GM) BLL was 7.54 µg/dL (95% CI: 6.77, 8.31). Children's BLLs displayed a decreasing temporal trend, from 11.77 µg/dL in phase I (2004-2006) to 4.63 µg/dL in phase V (2016-2018). Almost 95% of eligible studies found that children exposed to e-waste had significantly higher BLLs than reference groups. The difference of children's BLLs between the exposure group and the reference group was from 6.60 µg/dL (95% CI: 6.14, 7.05) in 2004 to 1.99 µg/dL (95% CI: 1.61, 2.36) in 2018. For subgroup analyses, except for Dhaka and Montevideo, the BLLs of children from Guiyu in the same survey year were higher than those of children from other regions. Our findings indicate that the gap between BLLs of children exposed to e-waste and those of reference group children is closing, and we appeal that the critical value for blood lead poisoning in children should be lowered in key e-waste-dismantling areas of developing countries, such as Guiyu.

CXCL9, 10, 11/CXCR3 Axis Contributes to the Progress of Primary Sjogren's Syndrome by Activating GRK2 to Promote T Lymphocyte Migration.

Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that causes dysfunction of secretory glands and the specific pathogenesis is still unknown. The CXCL9, 10, 11/CXCR3 axis and G protein-coupled receptor kinase 2 (GRK2) involved in many inflammation and immunity processes. We used NOD/Ltj mice, a spontaneous SS animal model, to elucidate the pathological mechanism of CXCL9, 10, 11/CXCR3 axis promoting T lymphocyte migration by activating GRK2 in pSS. We found that CD4 + GRK2, Th17 + CXCR3 was apparently increased and Treg + CXCR3 was significantly decreased in the spleen of 4W NOD mice without sicca symptom compared to ICR mice (control group). The protein levels of IFN-γ, CXCL9, 10, 11 increased in submandibular gland (SG) tissue accompanied by obvious lymphocytic infiltration and Th17 cells overwhelmingly infiltrated relative to Treg cells at the sicca symptom occurs, and we found that the proportion of Th17 cells was increased, whereas that of Treg cells was decreased in spleen. In vitro, we used IFN-γ to stimulate human salivary gland epithelial cells (HSGECs) co-cultured with Jurkat cells, and the results showed that CXCL9, 10, 11 was increased by IFN-γ activating JAK2/STAT1 signal pathway and Jurkat cell migration increased with the raised of cell membrane GRK2 expression. HSGECs with tofacitinib or Jurkat cells with GRK2 siRNA can reduce the migration of Jurkat cells. The results indicate that CXCL9, 10, 11 significantly increased in SG tissue through IFN-γ stimulating HSGECs, and the CXCL9, 10, 11/CXCR3 axis contributes to the progress of pSS by activating GRK2 to promote T lymphocyte migration.

Epidemiological evidence for the effect of environmental heavy metal exposure on the immune system in children.

Heavy metals exist widely in daily life, and exposure to heavy metals caused by environmental pollution has become a serious public health problem worldwide. Due to children's age-specific behavioral characteristics and imperfect physical function, the adverse health effects of heavy metals on children are much higher than in adults. Studies have found that heavy metal exposure is associated with low immune function in children. Although there are reviews describing the evidence for the adverse effects of heavy metal exposure on the immune system in children, the summary of evidence from epidemiological studies involving the level of immune molecules is not comprehensive. Therefore, this review summarizes the current epidemiological study on the effect of heavy metal exposure on childhood immune function from multiple perspectives, emphasizing its risks to the health of children's immune systems. It focuses on the effects of six heavy metals (lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), nickel (Ni), and manganese (Mn)) on children's innate immune cells, lymphocytes and their subpopulations, cytokines, total and specific immunoglobulins, and explores the immunotoxicological effects of heavy metals. The review finds that exposure to heavy metals, particularly Pb, Cd, As, and Hg, not only reduced lymphocyte numbers and suppressed adaptive immune responses in children, but also altered the innate immune response to impair the body's ability to fight pathogens. Epidemiological evidence suggests that heavy metal exposure alters cytokine levels and is associated with the development of inflammatory responses in children. Pb, As, and Hg exposure was associated with vaccination failure and decreased antibody titers, and increased risk of immune-related diseases in children by altering specific immunoglobulin levels. Cd, Ni and Mn showed activation effects on the immune response to childhood vaccination. Exposure age, sex, nutritional status, and co-exposure may influence the effects of heavy metals on immune function in children.

Current status of indoor dust PBDE pollution and its physical burden and health effects on children.

Polybrominated diphenyl ethers (PBDEs) are widely detected in indoor dust, which has been identified as a more important route of PBDE exposure for children than food intake. The physical burden and health hazards to children of PBDE exposure in house dust have not been adequately summarized; therefore, this article reviews the current status of PBDE pollution in indoor dust associated with children, highlighting the epidemiological evidence for physical burden and health risks in children. We find that PBDEs remain at high levels in indoor dust, including in homes, schools, and cars, especially in cars showing a significant upward trend. There is a trend towards an increase in the proportion of BDE-209 in household dust, which is indicative of recent PBDE contamination. Conversely, PBDE congeners in car and school indoor dust tended to shift from highly brominated to low brominated, suggesting a shift in current pollution patterns. Indoor dust exposure causes significantly higher PBDE burdens in children, especially infants in early life, than in adults. Exposure to dust also affects breast milk, putting infants at high risk of exposure. Although evidence is limited, available epidemiological studies suggest that exposure to indoor dust PBDEs promotes neurobehavioral problems and cancer development in children.

Kindergarten indoor dust metal(loid) exposure associates with elevated risk of anemia in children.

Exposure to metals and metalloids in indoor dust is associated with adverse health effects in young children, but there is limited evidence for an association with anemia, which is at high risk in children. The aim of this study was to investigate the association between exposure to multiple metal(loid)s in indoor dust in kindergartens and the risk of anemia in children. In 2021, 2165 children from 25 kindergartens in eastern China were included in the study and had their hemoglobin (Hb) measured. Indoor dust samples were collected from the children's kindergartens, and the concentrations of 11 metals and metalloids in the samples were measured using inductively coupled plasma mass spectrometry (ICP-MS). The daily exposure dose (DED) of dust was used to assess the risk of metal(loid) exposure in the children. The results showed that of the 2165 children with available data, 351 (16.2 %) met the WHO definition of anemia. In multiple linear regression and logistic regression analyses, we found that for each quartile of DED increase in Cd inhalation, child Hb levels decreased by 2.703 g/L (95 % CI: -4.055, -1.351), and the risk of anemia increased 1.602-fold (95 % CI: 1.087, 2.360). Mn ingestion was associated with increased odds of anemia [odds ratio (OR) = 1.760 (95 % CI: 1.217, 2.544)]. Interaction analysis indicated that metal(loid)s exposure effects were modified by child sex, age, and body mass index (BMI). Cluster analysis found that children at high risk of metal(loid) exposure in the school environment tended to have lower Hb levels and higher prevalence of anemia compared with those at low risk, although this was not statistically significant. These findings suggest that child school exposure to metal(loid)s in indoor dust is associated with an increased risk of developing anemia in children, modified by child sex, age, and BMI.

Deficiency of ß-arrestin2 alleviates apoptosis through GRP78-ATF6-CHOP signaling pathway in primary Sjögren's syndrome.

The etiology of primary Sjögren's syndrome (pSS) remains unknown, and there is no ideal drug for the specific treatment of pSS. ß-arrestin2 is a key protein that mediates desensitization and internalization of G protein-coupled receptors (GPCRs) and it participates in inflammatory and immune responses that have been found to mediate apoptosis in autoimmune disease. In this study, we established an experimental Sjögren's syndrome (ESS) mouse model to elucidate the molecular mechanisms of ß-arrestin2 in pSS. First, excessive activation of ß-arrestin2 and GRP78-ATF6-CHOP apoptosis signaling were detected in specimens from pSS patients. In vivo, we found that inhibition of GRP78-ATF6-CHOP apoptosis signaling improved ESS symptoms, and the targeted deletion of ß-arrestin2 significantly increased saliva flow, alleviated salivary gland indices, and improved tissue integrity in the ESS model by downregulating GRP78-ATF6-CHOP apoptosis signaling. In vitro, we used IFNα to stimulate human salivary gland epithelial cells (HSGECs), and the results showed that IFNα activated GRP78-ATF6-CHOP apoptosis signaling, decreased cell viability, and induced apoptosis, which were negatively regulated by the ERS inhibitor 4-PBA. In addition, ß-arrestin2 depletion downregulated GRP78-ATF6-CHOP apoptosis signaling to alleviate cell apoptosis, and the effect depended on the interaction between GRP78 and ß-arrestin2. In summary, our results suggest that excessive activation of GRP78-ATF6-CHOP apoptosis signaling is involved in the pathogenesis of pSS and that ß-arrestin2 encourages inflammation-induced epithelial apoptosis through GRP78-ATF6-CHOP apoptosis signaling. This research further clarified the underlying role of ß-arrestin2 and provided an experimental foundation for ß-arrestin2 depletion in the treatment of the human autoimmune disorder pSS.