1.Lead exposure promotes NF2-wildtype meningioma cell proliferation through the Merlin-Hippo signaling pathway.
Nenghua ZHANG ; Xiaohua SHEN ; Yunnong YU ; Long XU ; Zheng WANG ; Jia ZHU
Environmental Health and Preventive Medicine 2025;30():8-8
BACKGROUND:
Lead is a persistent inorganic environmental pollutant with global implication for human health. Among the diseases associated with lead exposure, the damage to the central nervous system has received considerable attention. It has been reported that long-term lead exposure increases the risk of meningioma; however, the underlying mechanism remains poorly understood. Clinical studies have indicated that loss-of-function and mutations in the neurofibromin-2 (NF2) gene play a crucial role in promoting meningioma formation.
METHODS:
The effect of Pb on meningioma were tested in-vitro and in-vivo. Two human meningioma cell lines were used in this study, including NF2-wildtype IOMM-Lee cell and NF2-null CH157-MN cell. Cell viability, cell cycle and cell size were examined after Pb exposure. The expression of Merlin, mammalian sterile 20-like kinases 1 and 2 (MST1/2) and Yes-associated protein (YAP) from these two meningioma cells were analyzed by Western blot. A xenograft mouse model was constructed by subcutaneous injection of IOMM-Lee meningioma cells.
RESULTS:
This study demonstrated that treatment with lead induce dose-dependent proliferation in IOMM-Lee cell (with an EC50 value of 19.6 µM). Moreover, IOMM-Lee cell exhibited augmented cell size in conjunction with elevated levels of phosphorylated histone H3, indicative of altered cell cycle progression resulting from lead exposure. However, no significant change was observed in the CH157-MN cell. Additionally, the Merlin-Hippo signaling pathway was inactivated with decreased Merlin and phosphorylation levels of MST1/2 and YAP, leading to increased YAP nuclear translocation in IOMM-Lee cells. However, there was no change in the Merlin-Hippo signaling pathway in CH157-MN cells after lead treatment. The administration of Pb resulted in an acceleration of the subcutaneous IOMM-Lee meningioma xenograft growth in mice.
CONCLUSIONS
Overall, the current study elucidates the potential mechanism by which lead exposure promotes the proliferation of meningioma with NF2 expression for the first time.
Meningioma/genetics*
;
Neurofibromin 2/genetics*
;
Humans
;
Cell Proliferation/drug effects*
;
Animals
;
Signal Transduction/drug effects*
;
Mice
;
Hippo Signaling Pathway
;
Lead/adverse effects*
;
Cell Line, Tumor
;
Protein Serine-Threonine Kinases/genetics*
;
Meningeal Neoplasms
;
Environmental Pollutants/adverse effects*
;
Female
2.Association between maternal blood lead levels and prevalence of dental caries in the primary dentition of children.
Yoshie NAGAI-YOSHIOKA ; Ryota YAMASAKI ; Reiko SUGA ; Mayumi TSUJI ; Reiji FUKANO ; Kiyoshi YOSHINO ; Seiichi MOROKUMA ; Wataru ARIYOSHI ; Masanori IWASAKI
Environmental Health and Preventive Medicine 2025;30():92-92
BACKGROUND:
Dental caries is a chronic childhood disease and one of the most prevalent public health problems worldwide. Lead is a heavy metal that is taken up by the teeth and bones. However, the association between lead exposure during pregnancy, when the tooth germs are formed, and the prevalence of dental caries in the primary dentition remains unclear. This study aimed to examine the association between maternal blood lead levels and the prevalence of dental caries in the primary dentition of children.
METHODS:
This cross-sectional study was conducted as an Adjunct Study to the Japan Environment and Children's Study (JECS), which is an ongoing nationwide birth-cohort study. Among children participating in the JECS at the University of Occupational and Environmental Health Sub-Regional Center, those aged 7-8 years underwent oral examination and questionnaire administration. The dft (i.e., sum of the number of decayed and filled primary teeth) was then determined. The dft numerically expresses the dental caries prevalence in the primary dentition (larger value indicates more prevalent dental caries). Poisson regression analyses with robust standard errors were performed to evaluate the association between maternal blood lead levels during pregnancy, measured using frozen samples, and the dft.
RESULTS:
The study included 139 children, of whom 54.7% were girls, and 89.2% were 7 years old. The median maternal blood lead level was 6.1 ng/g (25-75 percentile, 5.0-7.3). The median dft was 0 (25-75 percentile, 0-4). After adjusting for covariates including age, sex, and oral health status and behavior, maternal blood lead levels were significantly associated with increased dft (prevalence ratio, 1.6; 95% confidence interval, 1.3-1.8; per one standard deviation increase in natural log-transformed maternal blood lead levels).
CONCLUSIONS
This study found an association between maternal blood lead levels and the prevalence of dental caries in the primary dentition of children aged 7-8 years. Maternal exposure to lead during mid- to late-term pregnancy may affect the caries susceptibility of children after birth.
Humans
;
Lead/blood*
;
Female
;
Dental Caries/epidemiology*
;
Prevalence
;
Tooth, Deciduous
;
Male
;
Japan/epidemiology*
;
Child
;
Cross-Sectional Studies
;
Pregnancy
;
Adult
;
Maternal Exposure/adverse effects*
;
Environmental Pollutants/blood*
;
Prenatal Exposure Delayed Effects/epidemiology*
3.Research progress on metal pollutants inducing neurotoxicity through ferroptosis.
Ziyu QIN ; Yuqing CHEN ; Xinyuan ZHAO ; Shali YU
Journal of Zhejiang University. Medical sciences 2024;53(6):699-707
It has been confirmed that exposure to various metal pollutants can induce neurotoxicity, which is closely associated with the occurrence and development of neurological disorders. Ferroptosis is a form of cell death in response to metal pollutant exposure and it is closely related to oxidative stress, iron metabolism and lipid peroxidation. Recent studies have revealed that ferroptosis plays a significant role in the neurotoxicity induced by metals such as lead, cadmium, manganese, nickel, and antimony. Lead exposure triggers ferroptosis through oxidative stress, iron metabolism disorder and inflammation. Cadmium can induce ferroptosis through iron metabolism, oxidative stress and ferroptosis related signaling pathways. Manganese can promote ferroptosis through mitochondrial dysfunction, iron metabolism disorder and oxidative stress. Nickel can promote ferroptosis by influencing mitochondrial function, disrupting iron homeostasis and facilitating lipid peroxidation in the central nervous system. Antimony exposure can induce glutathione depletion by activating iron autophagy, resulting in excessive intracellular iron deposition and ultimately causing ferroptosis. This article reviews the effects of metal pollutants on ferroptosis-related indicators and discusses the specific mechanisms by which each metal triggers ferroptosis. It provides a reference for identifying targets for preventing neurotoxicity and for developing treatment strategies for neurological disorders.
Ferroptosis/drug effects*
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Humans
;
Iron/metabolism*
;
Oxidative Stress/drug effects*
;
Neurotoxicity Syndromes/metabolism*
;
Cadmium/adverse effects*
;
Animals
;
Lipid Peroxidation/drug effects*
;
Metals/metabolism*
;
Lead/adverse effects*
;
Environmental Pollutants/toxicity*
;
Manganese/adverse effects*
;
Nickel/adverse effects*
;
Mitochondria/drug effects*
;
Signal Transduction/drug effects*
4.Spatial correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in a typical coal-fired pollution fluorosis area.
Jian Ying WANG ; Jian Zhong CHENG ; Na YANG ; Jiang Hui ZHANG ; Cheng Long TU
Chinese Journal of Epidemiology 2023;44(6):891-898
Objective: To investigate the spatial distribution characteristics and correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in coal-fired fluorosis areas. Methods: Based on the survey data on the prevalence of dental fluorosis at CDC in Guizhou Province in 2022, 274 original surface drinking water sources were collected in typical coal-fired fluorosis areas, and fluoride (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb) 17 elements; apply Moran's I index, Getis-Ord Gi* hotspot analysis of the global spatial autocorrelation of chemical elements in drinking water and the degree of aggregation of each element on the local area, and correlation analysis with the prevalence of dental fluorosis in the region. Results: Except for Cu, Zn, and Cd, global spatial autocorrelation Moran's I was negative, and all other elements were positive. F, Ca, Al, Ti, As, Mo, Cd, and Cu elements showed high values of aggregation in the southeastern low-altitude area; Mg, Ba, Pb, Cr, Mn, and Fe elements were mainly aggregated in the central altitude terrain transition area, Zn and Se elements in water sources are significantly positively correlated with the prevalence of dental fluorosis (P<0.05). In contrast, F, Mg, Al, Ti, As, Mo, Cd, Ba, and Pb elements negatively correlate (P<0.05). Elements in the central region were high-high aggregation, as a hot spot aggregation area with high disease incidence, while F, Al, Mn, Mo, Cd, and Ba elements in the western region were low-low aggregation, as a cold spot aggregation area with a low incidence of fluorosis. Conclusions: The risk of population fluoride exposure in surface drinking water sources is shallow. However, the chemical element content of drinking water sources in coal-fired polluted endemic fluorosis areas has prominent spatial geographical distribution characteristics. There is a significant spatial aggregation effect with the prevalence of dental fluorosis, which may play a synergistic or antagonistic effect on the occurrence and prevalence of dental fluorosis.
Humans
;
Drinking Water
;
Prevalence
;
Coal
;
Fluorides/adverse effects*
;
Cadmium
;
Fluorosis, Dental/epidemiology*
;
Lead
;
Selenium
;
Arsenic
5.Outbreak investigation of lead neurotoxicity in children from artificial jewelry cottage industry.
Akhil D GOEL ; Rohini V CHOWGULE
Environmental Health and Preventive Medicine 2019;24(1):30-30
BACKGROUND:
Although lead neurotoxicity is a known phenomenon, it can often be missed at a primary or secondary care level especially if detailed environmental exposure history is missed.
METHODS:
This is an outbreak investigation where we observed 15 pediatric cases with neurologic signs and symptoms clustered in a slum area known for an unorganized artificial jewelry industry. Their clinical, biochemical, and epidemiological features were compared with 14 other children from the same region reporting with non-neurological symptoms who were considered as unmatched controls.
RESULTS:
Cases with neurological manifestations had a higher in-house lead smelting activity [OR 7.2 (95% CI 1.4-38.3)] as compared to controls. Toddlers below 3 years of age were more vulnerable to the effects of lead.
CONCLUSION
This study emphasizes that many focal sources of lead poisoning still remain especially in the unorganized sector. In cases presenting with unexplained neurotoxicity, specific occupational and environmental inquiry for chemical poisoning, with special consideration for lead, should be actively pursued.
Adolescent
;
Air Pollution, Indoor
;
adverse effects
;
Case-Control Studies
;
Child
;
Child, Preschool
;
Disease Outbreaks
;
Female
;
Humans
;
India
;
epidemiology
;
Infant
;
Inhalation Exposure
;
adverse effects
;
Jewelry
;
poisoning
;
Lead
;
blood
;
standards
;
Lead Poisoning
;
epidemiology
;
pathology
;
physiopathology
;
Male
;
Metallurgy
;
Neurotoxicity Syndromes
;
epidemiology
;
pathology
;
physiopathology
;
Poverty Areas
;
Risk Factors
6.Progress in research of relationship between heavy metal exposure and cardiovascular disease.
F LU ; F ZHAO ; J Y CAI ; L LIU ; X M SHI
Chinese Journal of Epidemiology 2018;39(1):102-106
Heavy metal is one of pollutants existed widely in the environment, its relationship with cardiovascular disease has attracted more and more attention. In this review, the concentrations of heavy metals, including lead, cadium and asenic, in the body from several national surveillance networks and the epidemiological studies on the effects of the exposure of three heavy metals on cardiovascular system were summarized. It is suggested to strengthen nationwide surveillance for body concentrations of heavy metals in general population in order to provide baseline data for quantitative evaluation of the risk of heavy metal exposure on cardiovascular disease.
Cadmium
;
Cardiovascular Diseases/chemically induced*
;
Environmental Exposure/adverse effects*
;
Environmental Pollutants/toxicity*
;
Epidemiologic Studies
;
Humans
;
Lead/toxicity*
;
Metals, Heavy/toxicity*
;
Neoplasms
;
Research/trends*
7.Effect of parents' occupational and life environment exposure during six months before pregnancy on executive function of preschool children.
Lingling NI ; Ting SHAO ; Huihui TAO ; Yanli SUN ; Shuangqin YAN ; Chunli GU ; Hui CAO ; Kun HUANG ; Fangbiao TAO ; Shilu TONG
Chinese Journal of Preventive Medicine 2016;50(2):136-142
OBJECTIVETo examine the effect of parents' occupational and life exposure during six months before pregnancy on executive function of preschool children.
METHODSPregnant women involved in the study came from the Ma'anshan Birth Cohort Study,a part of the China-Anhui Birth Cohort Study. Between October 2008 and October 2010, pregnant women who accepted pregnancy care in four municipal medical and health institutions in Ma'anshan city were recruited as study objects. A total of 5,084 pregnant women and 4,669 singleton live births entered in this cohort. Between April 2014 and April 2015, a total of 3,803 pre-school children were followed up. Finally, except 32 preschool children did not have EF evaluation result, there were 3,771 children included in this study. By using self-designed " Maternal health handbook", we researched parents' general demographic characteristics, and life and occupational exposure during six months before pregnancy. To research preschool children's executive function, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the association of parents' life and occupational exposure during six months before pregnancy and preschool children's EF.
RESULTS3,771 preschool children's detected rate of inhibitory self-control index (ISCI), flexibility index (FI), emergent metacognition index (EMI) and global executive composite (GEC) dysplasia were 4.8% (182), 2.3% (88), 16.5% (623) and 8.6% (324) respectively. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.86, 95% CI: 1.36-2.54), whose maternal were exposed to pesticides were the risk of ISCI dysplasia(OR=3.60, 95% CI: 1.45-8.95). During six months before pregnancy, children whose maternal were exposed to pesticides (OR=6.72, 95% CI: 2.50-18.07) and whose father were exposed to occupational lead (OR=2.10, 95% CI: 1.25-3.54) were the risk of FI dysplasia. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.42, 95%CI: 1.18-1.71) and whose father were exposed to occupational lead (OR=1.30, 95%CI: 1.02-1.65) were the risk of EMI dysplasia. During six months before pregnancy, children whose parents were lived in a noise environment (OR=1.58, 95% CI: 1.24-2.01) and whose maternal were exposed to pesticides (OR=2.39, 95% CI: 1.02-5.58) were the risk of GEC dysplasia.
CONCLUSIONThe development of executive function is worse among preschool children whose parents live in noise environment, mother exposed to pesticides, and father exposed to occupational lead during six months before pregnancy.
Child ; Child, Preschool ; China ; Cohort Studies ; Environmental Exposure ; adverse effects ; Executive Function ; Family Characteristics ; Female ; Humans ; Lead ; adverse effects ; Male ; Occupational Exposure ; adverse effects ; Parents ; Pesticides ; adverse effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; epidemiology ; psychology
8.Effects of nano-lead exposure on learning and memory as well as iron homeostasis in brain of offspring rats.
Jing GAO ; Hong SU ; Jingwen YIN ; Fuyuan CAO ; Peipei FENG ; Nan LIU ; Ling XUE ; Guoying ZHENG ; Qingzhao LI ; Yanshu ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2015;33(6):409-413
OBJECTIVETo investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42).
METHODSTwenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay.
RESULTSAfter nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05).
ONCLUSIONn Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.
Animals ; Cerebral Cortex ; drug effects ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Homeostasis ; Iron ; metabolism ; Lead ; toxicity ; Learning ; drug effects ; Maternal Exposure ; adverse effects ; Memory ; drug effects ; Pregnancy ; Rats ; Rats, Sprague-Dawley
9.Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area.
Yan YANG ; Xiao Song LU ; Ding Long LI ; Yun Jiang YU
Biomedical and Environmental Sciences 2013;26(6):474-484
OBJECTIVETo study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels.
METHODSAn E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied.
RESULTSThe blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks.
CONCLUSIONThere was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks.
Adult ; Electronic Waste ; analysis ; Environmental Monitoring ; Environmental Pollutants ; blood ; chemistry ; Follicle Stimulating Hormone ; blood ; Gonadal Steroid Hormones ; blood ; Humans ; Lead ; blood ; chemistry ; Luteinizing Hormone ; blood ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Refuse Disposal ; methods ; Testosterone ; blood

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