MiR-378a-3p/ SLC7A11 regulate ferroptosis in nerve injury induced by lead exposure.

An increasing number of studies have clarified that ferroptosis plays a vital role in neurodegenerative diseases, which is characterized by the accumulation of Fe2+, lipid peroxidation, and alteration of mitochondrial structure. However, whether ferroptosis is involved in nerve injury caused by lead exposure remains unclear. In this study, HT22 cells and mice were treated with lead acetate to investigate the role of ferroptosis in lead neurotoxicity. The results showed that lead exposure resulted in an accumulation of Fe2+, an increase in malondialdehyde (MDA) levels, and a decrease in glutathione (GSH) levels in vivo and in vitro. An increase in the levels of lipid reactive oxygen species (ROS) and the expression of 4HNE, as well as the change in mitochondrial morphology, were also observed in HT22 cells treated with lead acetate. In addition, deferoxamine (DFO; an iron chelator) attenuated the accumulation of Fe2+ and significantly enhanced the viability of HT22 cells exposed to lead. Fer-1 (an anti-ferroptosis agent) reduced the level of lipid ROS and expression of 4HNE in lead-treated HT22 cells. Furthermore, lead exposure sharply downregulated the expression of SLC7A11 in HT22 cells. Overexpression of SLC7A11 reversed the changes in MDA and GSH levels and cell viability induced by lead exposure. In contrast, lower expression of SLC7A11 accelerated the changes in these parameters. Consequently, we screened miRNAs that regulate SLC7A11 using TargetScan. We found that miR-378a-3p showed the highest expression among the target miRNAs regulating SLC7A11 expression. Inhibition of miR-378a-3p expression reversed the reduction in GSH and the increase in lipid ROS levels induced by lead exposure. Taken together, these findings indicate that lead exposure can cause ferroptosis and that miR-378a-3p exerted an important effect by regulating SLC7A11 expression. Our findings provide new insights into the mechanisms underlying the effects of lead exposure.

Brain copper clearance by the blood-cerebrospinal fluid-barrier: Effects of lead exposure.

Lead (Pb) is a heavy metal commonly found in the environment and is known to have neurotoxic, hematological, and other toxic effects. It has been reported that Pb exposure can disturb metal regulation in the blood-cerebrospinal fluid-barrier (BCB). Copper (Cu) plays a key role in maintaining normal brain function and can accumulate in the brain after Pb exposure. However, the mechanism by which Pb affects Cu levels in the brain is still unknown. This study investigated Cu clearance by the BCB in the central nervous system (CNS) of Sprague-Dawley rats after Pb exposure by focusing on the Cu transporter protein CTR1/ATP7A. Inductively coupled plasma mass spectrometry (ICP-MS) was used to examine how heavy metal levels change in the hippocampus, cortex, and cerebrospinal fluid (CSF) after Pb exposure. Ventriculo-cisternal perfusion measurements suggested that the ability of the BCB to deliver Cu from the CSF to the blood decreased after Pb exposure. The presence of excess Cu in the choroid plexus led to CTR1/ATP7A shifting toward the apical microvilli facing the CSF after Pb exposure. We further evaluated microstructure of the choroid plexus by transmission electron microscopy, revealing altered mitochondrial morphology with decreased microvilli after Pb exposure. Conclusively, exposure to Pb alters the cellular structure of the BCB and its Cu clearance function, which can cause further brain damage.

SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity.

Structural maintenance of chromosomes 4 (SMC4) has an important role in chromosome condensation and segregation, which is involved in regulating multiple tumor development. However, the role of SMC4 in endometrial cancer is uncertain. The expression and prognostic value of SMC4 were predicted by UALCAN, Gene Expression Omnibus (GEO), The Human Protein Atlas and Kaplan Meier plotter tools. SMC4-related genes were analyzed by LinkedOmics, Gene Ontology (GO) annotations, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Forkhead box protein O1 (FoxO1) activity was suppressed by AS1842856 (AS). SMC4, Ki67, B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein (Bax), FoxO1, phosphorylated FoxO1 (p-FoxO1), and p27 protein levels were detected by Western blotting. Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) analyses. Cell apoptosis was measured using TUNEL analysis. SMC4 abundance was increased in endometrial cancer, and predicted a worse overall survival. SMC4 knockdown repressed proliferative ability of endometrial cancer cells and promoted cell apoptosis. SMC4 knockdown promoted FoxO1 transactivation by decreasing its phosphorylated level. Addition of AS inhibited FoxO1 activity by increasing the phosphorylated level of FoxO1. The inhibition of FoxO1 activity reversed the effect of SMC4 silencing on cell proliferation and apoptosis. In conclusion, SMC4 silencing restrained cell proliferation and facilitated apoptosis in endometrial cancer via regulating FoxO1 activity.

Effects of lead exposure on the activation of microglia in mice fed with high-fat diets.

Lead (Pb) exposure can cause central nervous system (CNS) damage. The process of Pb neurotoxicity is accompanied by the microglia activation. In addition, microglia activation was observed under the intervention of high-fat diets (HFD). This study was designed to investigate the effect of Pb on the cognitive function of mice with HFD, with focus on the microglia activation in brain. Male C57BL/6J mice, 8 weeks of age, were randomly divided into control, HFD, Pb, and HFD + Pb groups. The results showed that HFD following Pb exposure could exacerbate the learning and memory impairment in mice. Pb exposure could promote microglia activation and increase the expression of M1 microglia marker and decrease the expression of M2 microglia marker in the hippocampus of mice with HFD. Our finding suggested that Pb exposure may aggravate CNS damage by promoting M1 polarization and inhibiting M2 polarization of hippocampal microglia in HFD mice.

Evaluation of a Drowning Prevention Program Based on Testimonial Videos: A Randomized Controlled Trial.

OBJECTIVE: Unintentional drowning is the most common cause of childhood death in rural China. Global intervention efforts offer mixed results regarding the efficacy of educational programs. METHODS: Using a randomized controlled design, we evaluated a testimonial-based intervention to reduce drowning risk among 280 3rd- and 4th-grade rural Chinese children. Children were randomly assigned to view either testimonials on drowning risk (intervention) or dog-bite risk (control). Safety knowledge and perceived vulnerability were measured by self-report questionnaires, and simulated behaviors in and near water were assessed with a culturally appropriate dollhouse task. RESULTS: Children in the intervention group had improved children's safety knowledge and simulated behaviors but not perceived vulnerability compared with controls. CONCLUSIONS: The testimonial-based intervention's efficacy appears promising, as it improved safety knowledge and simulated risk behaviors with water among rural Chinese children.

A randomized trial evaluating child dog-bite prevention in rural China through video-based testimonials.

OBJECTIVE: Dog-bite injuries pose significant threat to children globally. School-age children are especially at risk because of their insufficient safety knowledge and cognitively immature tendency toward low perceived vulnerability to bites, and this risk is elevated further for school-age children living in rural China due to the large number of stray dogs, all potential rabies carriers, present in their communities. METHOD: This randomized controlled trial evaluated whether viewing an educational video of testimonials would change safety knowledge, perceived vulnerability, and simulated behaviors with dogs among a sample of 280 third and fourth graders living in rural China. Participants were randomly assigned to view either an educational video of testimonials on dog-bite prevention (treatment) or an educational video of testimonials on drowning prevention (comparison). Safety knowledge, perceived vulnerability to dog bites, and simulated behavior with dogs using a dollhouse model were assessed both before and after exposure to the video of testimonials. RESULTS: Children who watched the educational video of testimonials on dog-bite prevention had increased safety knowledge, higher perceived vulnerability, and less risky simulated behaviors with dogs compared with the comparison group. Mediation analysis revealed that the intervention successfully changed children's simulated behaviors with dogs through greater safety knowledge and increased perceived vulnerability. CONCLUSIONS: Results suggest the incorporation of testimonials into injury prevention programs has potential for broad global dissemination. The fact that both increased knowledge and heightened perceived vulnerability mediated changes in simulated behavior suggests the dual roles of knowledge and appraisal on children's injury-risk behavior.

Cognitive and Behavioral Risk Factors for Unintentional Drowning Among Rural Chinese Children.

BACKGROUND: Unintentional drowning is among the top causes of pediatric death worldwide and the leading cause of death for children under age 14 in China. Environmental factors such as abundant bodies of water and psychosocial factors such as lack of parental supervision contribute to heightened risk of pediatric drowning in rural China, but little is known about the role of individual characteristics such as knowledge and perceived vulnerability in the drowning risk of rural Chinese children. PURPOSE: The present study aimed to explore the cognitive and behavioral risk factors for unintentional drowning among school-aged rural Chinese children. METHOD: Two hundred and eighty children (mean age = 10.03 years, range 8-13) enrolled at an elementary school in rural Zhejiang Province, China completed self-report assessments of knowledge about drowning prevention, perceived vulnerability toward drowning, and history of non-fatal drowning experiences, as well as demographic information. A simulation task using a dollhouse assessed children's anticipated behaviors with water. RESULTS: Fifty-two percent of the sample reported exposure to water sources at least once daily, and 21 % of the sample reported at least one non-fatal drowning experience in their lifetime. Regression analysis showed that male gender, better swimming ability, less safety knowledge, and lower levels of perceived vulnerability were associated with more self-reported risky practice in/near water. More safety knowledge also predicted safer behaviors in the dollhouse simulation task. None of the risk factors predicted self-reported history of non-fatal drowning incidents. CONCLUSION: High exposure to water sources and non-fatal drowning experiences were found among school-aged children in rural China. Drowning risk factors included demographic, cognitive, and behavioral characteristics of children. Results offer evidence for developing interventions in both Zhejiang Province and other regions with similar geographic and population characteristics.

[Effects of lead exposure on copper and copper transporters in choroid plexus of rats].

OBJECTIVE: To investigate the effects of lead exposure on the copper concentration in the brain and serum and the expression of copper transporters in the choroid plexus among rats. METHODS: Sixty specific pathogen-free Sprague-Dawley rats were randomly divided into a control group and three lead-exposed groups, with 8 mice in each group. The lead-exposed groups were orally administrated with 500 (low-dose group)), 1 000 (middle-dose group), and 2 000 mg/L (high-dose group) lead acetate in drinking water for eight weeks. And the rats in control group were given 2 000 mg/L sodium acetate in drinking water. The content of lead and copper in the serum, hippocampus, cortex, choroid plexus, bones, and cerebrospinal fluid (CSF) was determined by inductively coupled plasma-mass spectrometry (ICP-MS). Confocal and real-time PCR methods were applied to measure the expression of copper transporters including copper transporter 1 (Ctr1), antioxidant protein 1 (ATX1), and Cu ATPase (ATP7A). RESULTS: Compared with the control group, the lead-exposed groups showed significantly higher lead concentrations in the serum, cortex, hippocampus, choroid plexus, CSF, and bones (P < 0.05) and significantly higher copper concentrations in the CSF, choroid plexus, serum, and hippocampus (P < 0.05). Confocal images showed that Ctr1 protein was expressed in the cytoplasm and cell membrane of choroid plexus in control group. However, Ctr1 migrated to CSF surface microvilli after lead exposure. Ctr1 fluorescence intensity gradually increased with increasing dose of lead, except that the middle-dose group had a higher Ctr1 fluorescence intensity than the high-dose group. In addition, the middle- and high-dose groups showed a lower ATX1 fluorescence intensity compared with the control group. Real-time PCR data indicated that the three lead-exposed groups showed significantly higher mRNA levels of Ctr1 and ATP7A compared with the control group (P < 0.05). CONCLUSION: Copper homeostasis in the choroid plexus is affected by lead exposure to induce copper homeostasis disorders in brain tissue, which may be one of the mechanisms of lead neurotoxicity.

A survey of occupational health hazards among 7,610 female workers in China's electronics industry.

To investigate the occupational hazards among Chinese female workers in the electronics industry, the authors systematically sampled a total of 8,300 female workers at random across 4 provinces in a variety of electronics factories. A detailed questionnaire was used to collect information on occupational hazards and the occurrence of occupation-related diseases. The results show that 4,283 female workers (51.9%) were exposed to 1 or more occupational hazards. The most common chemical hazard was organic solvent, and the second most common was heavy metals. The ergonomic hazards included repetitive movements, poor standing posture, and the lifting of heavy goods. More than 60% of the female workers self-reported occupation-related diseases. These results showed that occupational health hazards were common in the electronics industry in China and that they caused serious occupation-related health problems for the female workers therein.

A multi-site study on knowledge, attitudes, beliefs and practice of child-dog interactions in rural China.

This study examines demographic, cognitive and behavioral factors that predict pediatric dog-bite injury risk in rural China. A total of 1,537 children (grades 4-6) in rural regions of Anhui, Hebei and Zhejiang Provinces, China completed self-report questionnaires assessing beliefs about and behaviors with dogs. The results showed that almost 30% of children reported a history of dog bites. Children answered 56% of dog-safety knowledge items correctly. Regressions revealed both demographic and cognitive/behavioral factors predicted children's risky interactions with dogs and dog-bite history. Boys behaved more riskily with dogs and were more frequently bitten. Older children reported greater risks with dogs and more bites. With demographics controlled, attitudes/beliefs of invulnerability, exposure frequency, and dog ownership predicted children's self-reported risky practice with dogs. Attitudes/beliefs of invulnerability, dog exposure, and dog ownership predicted dog bites. In conclusion, both demographic and cognitive/behavioral factors influenced rural Chinese children's dog-bite injury risk. Theory-based, empirically-supported intervention programs might reduce dog-bite injuries in rural China.