BIOLOGICAL TRACE ELEMENT RESEARCH
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2025
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IF 3.6
Liu Kan,Tao Tao,Li Ranhong,Wang Huanping,Wang Li,Wu Haiying
Arsenic exposure is well-established to cause neurotoxicity, but its underlying molecular mechanisms remain unclear. This study investigates the effects of early-life arsenic exposure on the nervous system of offspring. Female mice were exposed to NaAsO₂, and alterations in learning, memory, and hippocampal lesions in offspring were assessed. Transcriptome analysis, protein interaction studies, and cellular experiments were integrated to identify key regulatory factors in arsenic-induced neurotoxicity. Arsenic interacts with HUWE1, significantly downregulating its protein expression. HUWE1 inhibition enhances GPX8 stability by reducing its ubiquitination. GPX8 disrupts histone epigenetic modifications by promoting GSH synthesis and arsenic methylation, leading to elevated H3K9 levels. HUWE1 also interacts with KDM3A, and its inhibition reduces KDM3A-mediated H3K9me1/me2 demethylation, amplifying H3K9me2-mediated transcriptional repression of LARS2 and triggering PANoptosis. This study provides novel molecular insights into arsenic-induced neurotoxicity and highlights potential therapeutic targets to mitigate arsenic-related nervous system damage.
研究领域:
毒理学
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神经生物学
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表观遗传学
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分子毒理学
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发育神经科学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2024
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IF 6.7
Haorui Cao,Kang Mao,Jiajia Yang,Qingqing Wu,Jiming Hu,Hua Zhang
The arsM gene is a critical biomarker for the potential risk of arsenic exposure in paddy soil. However, on-site screening of arsM is limited by the lack of high-throughput point-of-use (POU) methods. Here, a multiplex CRISPR/Cas12a microfluidic paper-based analytical device (μPAD) was constructed for the high-throughput POU analysis of arsM, with cascade amplification driven by coupling crRNA-enhanced Cas12a and horseradish peroxidase (HRP)-modified probes. First, seven crRNAs were designed to recognize arsM, and their LODs and background signal intensities were evaluated. Next, a step-by-step iterative approach was utilized to develop and optimize coupling systems, which improved the sensitivity 32 times and eliminated background signal interference. Then, ssDNA reporters modified with HRP were introduced to further lower the LOD to 16 fM, and the assay results were visible to the naked eye. A multiplex channel microfluidic paper-based chip was developed for the reaction integration and simultaneous detection of 32 samples and generated a recovery rate between 87.70 and 114.05%, simplifying the pretreatment procedures and achieving high-throughput POU analysis. Finally, arsM in Wanshan paddy soil was screened on site, and the arsM abundance ranged from 1.05 × 106 to 6.49 × 107 copies/g; this result was not affected by the environmental indicators detected in the study. Thus, a coupling crRNA-based cascade amplification method for analyzing arsM was constructed, and a microfluidic device was developed that contains many more channels than previous paper chips, greatly improving the analytical performance in paddy soil samples and providing a promising tool for the on-site screening of arsM at large scales.
研究领域:
环境科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2021
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IF 7.086
Beibei Wang,Hongguang Cheng,Chunye Lin,Xuan Zhang,Xiaoli Duan,Qin Wang,Dongqun Xu
Emerging evidence indicates that chronic low-dose arsenic (As) exposure can pose adverse health effects to children. This study aimed to systematically study the exposure risk induced by As ingestion in children living in Hubei Province, central China. The feasibility of first morning spot urine instead of 24-h urine as an environmental exposure biomarker was also explored. A total of 120 children aged 2–17 years were recruited from an urban area for the collection of biomarker samples (first morning and 24-h urine samples), environmental exposure samples (duplicate diets, drinking water , and soil), and related child-specific exposure factors. The external exposure risk, internal exposure level, and source of exposure to As in children were analyzed. The results indicated that As concentration in duplicated diets, water, and soil were 29.2 μg kg −1 , 1.3 μg L −1 , and 9.3 mg kg −1 , respectively; these were all below the corresponding maximum allowable levels in China (the threshold value of As in most food, drinking water and soil are 0.5 mg⸱kg −1 , 0.01 mg L −1 , and 20 mg⸱kg −1 , respectively). Dietary intake was the predominant exposure route, accounting for 90% of the total daily dose. The combined oral non-carcinogenic and carcinogenic risks all exceeded the corresponding maximum acceptable risk level . Therefore, As bioavailability should be investigated and used in health risk assessment. Multiple linear regression analysis indicated that urinary As was positively associated with dietary As, with a one-unit increase in daily As intake from the diet associating with 4.82 and 5.21 μg g −1 increases in 24-h urine and first morning urine, respectively. Furthermore, significant correlations with 24-h urine and external exposure metrics suggested that creatine-adjusted As concentrations in first morning urine could be an appropriate substitute of 24-h urine as exposure biomarkers.
研究领域:
环境科学
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公共卫生
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毒理学
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DOI
高影响因子
Gut Microbes
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2025
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IF 11
Ruonan Chen,Xiaoqin Chai,Yunxiao Zhang,Tianxiu Zhou,Yinyin Xia,Xuejun Jiang,Bo Lv,Jun Zhang,Lixiao Zhou,Xin Tian,Ruonan Wang,Lejiao Mao,Feng Zhao,Hongyang Zhang,Jun Hu,Jingfu Qiu,Zhen Zou,Chengzhi Chen
Fat mass and obesity-associated protein (FTO) is the key demethylase that reverses the abnormally altered N6-methyladenosine (m6A) modification in eukaryotic cells under environmental pollutants exposure. Arsenic is an environmental metalloid and can cause severe symptoms in human mainly through drinking water. However, there is no specific treatment for its toxic effects due to the uncovered mechanisms. We previously revealed that exposure to arsenic increased the level of m6A via down-regulation of FTO, which might serve as a potential target for intervention against arsenic-related disorders. In this study, our results demonstrated that chronic exposure to arsenic significantly disrupted the intestinal barrier and microenvironment. Also, this administration resulted in the enhancement of m6A modification and the reduction of FTO expression in the intestine. By using both CRISPR/Cas9-based FTO knock-in strategy and adeno-associated virus (AAV)-mediated overexpression of FTO in the intestine, we established for the first time that up-regulation of FTO remarkably ameliorated arsenic-induced disruption of intestinal barriers and altered microenvironment of mice. We also firstly identified a dominant gut microbial species, Desulfovibrio fairfieldensis, which was sharply reduced in arsenic-exposed mice, was able to proceed arsenic-induced neurobehavioral impairments by declining the levels of its major metabolite hydrogen sulfide. Administration of Desulfovibrio fairfieldensis could significantly alleviate the neurotoxicity of arsenic. Intriguingly, the beneficial effects of FTO against arsenic neurotoxicity possibly occurred through a novel gut–brain communication via Desulfovibrio fairfieldensis and its produced hydrogen sulfide. Collectively, these findings will provide new ideas for understanding the mechanisms of arsenic-induced toxic effects from a gut–brain communication perspective, and will assist the development of explicit intervention strategy via regulation of a new potential target FTO for prevention and treatment against arsenic-related both intestinal and neurological disorders.
研究领域:
毒理学
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微生物学
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神经科学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2021
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IF 3.512
Nan Jing,Xinzheng Wang,Xin Yang,Qian Liu,Hongxia Wang,Fangting Dong,Kun He,Na Wang
With the acceleration of industrialization, environmental arsenic pollution is threatening human health. However, by the time clinical symptoms appear, arsenic toxicity has usually caused irreversible damage to the body, so it is important to establish a rapid and accurate screening method for early arsenic exposure. In this work, 32 female C57BL/6 mice were exposed to different concentrations of inorganic arsenic in drinking water for a week. By analyzing the changes in serum, more than 20 compounds were detected to increase or decrease with the increase of arsenic intake. The abnormal increase in inosine, xanthine, xanthosine, and hypoxanthine and the abnormal purine pathway were found at the same time. Dimethylarsenic acid, an important inorganic arsenic metabolite in the body, was also found in serum. Combined with statistical analysis, early arsenic exposure can be easily and quickly detected, and the potential health risks of short-term exposure can be revealed simultaneously.
研究领域:
环境科学
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毒理学
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分析化学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Cong Ma,Kaiqin Hu,Xueke Zhang,Yaru Yu,Zuying Xu,Tian Ma,Hongzhen Ruan,Yingying Zhang,Jiajia Wang,Xinyu Yue,Chunmei Liang,Huifen Xiang,Rui Guo,Yunxia Cao,Zhiming Ding
Arsenic is a pollutant that can cross the placenta; however, research on the effects of arsenic exposure during pregnancy on the fertility of female offspring is limited. To address this gap, we developed a mouse model to investigate the relationship between arsenic exposure during pregnancy and fertility in female offspring. Our fertility assessment revealed that gestational exposure to 1 mg/kg arsenic or higher (10 mg/kg) resulted in reduction in litter size, ovarian volume, and multistage-follicle number in female offspring. By assessing the in vitro developmental capacity of oocytes and zygotes, we confirmed that the reduced fertility was due not to impaired oocyte quality but rather to a reduction in oocyte quantity. Arsenic exposure impedes synapsis formation in MPI and compromises homologous recombination-mediated repair of double-strand breaks, resulting in fewer crossovers. This disruption activates the pachytene-checkpoint, hindering the progression of the MPI and resulting in the elimination of defective oocytes through p-Chk2 activation. Our study reveals for the first time the detrimental effects of arsenic exposure during pregnancy on the fertility of female offspring, underscoring the urgent need to prevent such exposure to safeguard reproductive health.
研究领域:
生殖生物学
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毒理学
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遗传学
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产品关联
DOI
PubMed
高影响因子
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