JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
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2024
·Vol. 79
·期 3
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IF 4.3
Wang He-Ling,Fang Evandro F
We are now living in an aging society with increasingly older population, many of whom are suffering with or are at a high risk of developing dementia (1,2). Alzheimer’s disease (AD) is the world’s most common type of dementia, affecting about 50 million individuals worldwide currently, with that number set to rise to 82 million by 2023. There is a huge challenge in developing an anti-AD drug, and an enormous amount of effort has been devoted to this branch of research. It is encouraging that the 2 recently described anti-Aβ antibodies, lecanemab and donanemab, show clear benefits in slowing cognitive decline in patients with early-stage disease; however, rare but severe side effects (such as brain bleeding and swelling) still occur (10.1126/science.adj8110), indicating that there is likely a longway to go in developing a cure for AD (3,4).Although the hunt is on to develop an anti-AD drug to stop disease progression, it is also important and necessary to focus on prevention. It has been reported that lifestyle patterns and environmental toxins (natural and anthropogenic) increase the risk of dementia, with some estimates noting up to a 30% increase in AD risk. These factors are modifiable and reducing such risks could prevent or slow down the onset of dementia (5,6). Environmental toxins cover a broad spectrum of chemicals, including pesticides (organochlorine and organophosphate insecticides), toxic metals (such as aluminum), air pollutants, and especially industrial chemicals (6). Although we are exposed to trace amount of these contaminants during our daily lives, a lifelong accumulation could presumably reach to a toxic level, jeopardizing neuronal function and brain health.Per- and polyfluoroalkyl substances (PFASs) are a group of man-made chemicals that have been widely used in consumer products around the world since the 1950s. They have been very widely used and closely linked to our daily lives, being used, for example, on fabrics to provide stain resistance, and on cookware to keep food from sticking to it. While PFAS compounds facilitate our lives, they have brought environmental challenges with them, mainly due to their broad application, vast numbers (there are thousands of fluoroalkyl chemical compounds), and due to a chain of linked carbon and fluorine atoms that result in very slow breakdown over time, a long lifespan (7). Due to its widespread use, humans have been widely exposed to these chemicals, many of which can now be found in blood and cerebrospinal fluid (CSF) samples. In combination with data from laboratory animals, it is suggested these chemicals may cause a series of health issues, as summarized in Figure 1 (7,8).In this issue, Delcourt and colleagues (9) present a small human study showing patients with high CSF PFASs correlate with AD. Here, using the CSF samples from 8 patients hospitalized with suspected normal pressure hydrocephalus, they checked levels of 18 of the most common PFAS molecules. PFASs were detected in all 8 CSF samples, and a correlation was seen between high PFOS (perfluorooctane sulfonate) and cognitive impairment among the tested individuals. This discovery brings with it a sense of urgency in reducing exposure to PFASs in our daily lives and highlights the risks that it may bring in terms of our brain health. As this is a small-size proof-of-concept study, further large-size clinical validation and underlying molecular investigation are needed.E.F.F. is supported by Cure Alzheimer’s Fund (#282952), HELSE SØR-ØST (#2020001, #2021021, #2023093), the Research Council of Norway (#262175, #334361), Molecule AG/VITADAO (#282942), NordForsk Foundation (#119986), the National Natural Science Foundation of China (#81971327), Akershus University Hospital (#269901, #261973, #262960), the Civitan Norges Forskningsfond for Alzheimers sykdom (#281931), the Czech Republic-Norway KAPPA programme (with Martin Vyhnálek, #TO01000215), the Rosa sløyfe/Norwegian Cancer Society & Norwegian Breast Cancer Society (#207819), and Wellcome Leap (#104617).E.F.F. is the co-owner of Fang-S Consultation AS (Organization number 931 410 717); he has an MTA with LMITO Therapeutics Inc. (South Korea), a CRADA arrangement with ChromaDex (United States), a commercialization agreement with Molecule AG/VITADAO; he is a consultant to Aladdin Healthcare Technologies (United Kingdom and Germany), the Vancouver Dementia Prevention Centre (Canada), Intellectual Labs (Norway), MindRank AI (China), and NYO3 (Norway and China). H-L.W. declares no conflict of interest.
研究领域:
神经科学
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环境健康
·
医学
✓ 已验证
DOI
PubMed
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
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2014
·
IF 2.235
Zhen-Qiang Shi,Xue-Lian Huang,Chen Wang,Yi-Fan Li,Chao He,Chang-Sheng Zhao
In this study, poly(ether sulfone) (PES)/poly(sodium acrylate) (PSA) hybrid particles for the removal of environmental toxins were prepared via in situ cross-linked polymerization coupled with a liquid–liquid phase separation technique. The particles were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). Batch experiments were performed to verify the adsorption capability of the particles, and the initial concentrations and pH values of the solutions significantly affected the adsorption process. In addition, both adsorption kinetic and adsorption isotherm models were used to analyze the adsorption process of Cu2+. The modified PES particles showed high adsorption capability for Cu2+ and methylene blue (MB), and a particle column was used to further study the removal ability of environmental toxins. The results indicated that the hybrid particles had great potential to remove heavy metal ions and cationic dyes for wastewater treatment on an industrial scale.
研究领域:
材料科学
·
环境科学
✓ 已验证
DOI
高影响因子
AQUACULTURE
·
2023
·
IF 4.5
Enzhuang Pan,Huimiao Feng,Zuwang Yang,Yue Xin,Xiaomeng Ji,Kaixin Ping,Yong Sun,Jingquan Dong
As a widely used fungicide at present, difenoconazole can enter the aquatic ecosystem and cause adverse effects on freshwater carp culture. The spleen, an important immune organ of carp, is vulnerable to damage by environmental toxins. Studies have shown that the inflammatory response is an important mechanism of immunotoxicity of difenoconazole. Whereas quercetin has anti-inflammatory pharmacological activity, the role and mechanism of quercetin in difenoconazole-induced inflammatory damage in the spleen of carp is unknown. In this study, we developed a model for carp with quercetin added to the diet and exposed to environmentally relevant concentrations of difenoconazole. We found that quercetin protects against inflammatory damage in the splenic tissue of carp through histopathological observations. We found that quercetin alleviated ROS enrichment and disruption of redox homeostasis (dynamic balance of GSH, T-AOC, CAT, and MDA) in the spleen tissue of carp by fluorescence assay and biochemical assay. We found that quercetin was able to inhibit the activation of the NF-κB signaling pathway (elevated p-NF-κB p65 expression level) and NLRP3 inflammasome pathway (NLRP3/ASC/caspase-1) in carp spleen tissue induced by difenoconazole by immunohistochemistry and qPCR analysis. In conclusion, this study confirms that the addition of quercetin as a supplement to the diets of freshwater cultured carp is effective against the spleen toxicity induced by difenoconazole. Mechanistically, quercetin may alleviate the difenoconazole-induced splenic inflammatory injury in carp by suppressing the excessive activation of ROS/NF-κB/NLRP3 inflammasome axis, providing new insights into the mechanism of quercetin alleviation of splenic inflammatory injury in carp.
研究领域:
水产养殖
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毒理学
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免疫学
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药理学
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2023
·
IF 17.1
Dongyu Xu,Yu Wang,Lingyu Sun,Zhiqiang Luo,Yuan Luo,Yongan Wang,Yuanjin Zhao
Environmental toxins can result in serious and fatal damage in the human heart, while the development of a viable stratagem for assessing the effects of environmental toxins on human cardiac tissue is still a challenge. Herein, we present a heart-on-a-chip based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured living anisotropic structural color hydrogels for cardiotoxicity screening. Such anisotropic structural color hydrogels with a conductive parallel carbon nanotube (CNT) upper layer, gelatin methacryloyl (GelMA) interlayer, and inverse opal bottom layer were fabricated by a sandwich replicating approach. The inverse opal structure endowed the anisotropic hydrogels with stable structural color property, while the parallel and conductive CNTs could induce the hiPSC-CMs to grow in a directional manner with consistent autonomous beating. Notably, the resultant hiPSC-CM-cultured hydrogel exhibited synchronous shifts in structural color, responding to contraction and relaxation of hiPSC-CMs, offering a visual platform for monitoring cell activity. Given these features, the hiPSC-CM-cultured living anisotropic structural color hydrogels were integrated into a heart-on-a-chip, which provided a superior cardiotoxicity screening platform for environmental toxins.
研究领域:
生物医学工程
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毒理学
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-12
·
IF 16.6
Li Bowei,Qi Ji,Liu Feng,Zhao Rongfang,Arabi Maryam,Ostovan Abbas,Song Jinming,Wang Xiaoyan,Zhang Zhiyang,Chen Lingxin
Fluorescence analysis is a fast and sensitive method, and has great potential application in trace detection of environmental toxins. However, many important environmental toxins are non-fluorescent substances, and it is still a challenge to construct a fluorescence detection method for non-fluorescent substances. Here, by means of charge transfer effect and smart molecular imprinting technology, we report a sensitive indirect fluorescent sensing mechanism (IFSM) and microcystin (MC-RR) is selected as a model target. A molecular imprinted thin film is immobilized on the surface of zinc ferrite nanoparticles (ZnFe 2 O 4 NPs) by using arginine, a dummy fragment of MC-RR. By implementation of IFSM on the paper-based microfluidic chip, a versatile platform for the quantitative assay of MC-RR is developed at trace level (the limit of detection of 0.43 μg/L and time of 20 min) in real water samples without any pretreatment. Importantly, the proposed IFSM can be easily modified and extended for the wide variety of species which lack direct interaction with the fluorescent substrate. This work offers the potential possibility to meet the requirements for the on-site analysis and may explore potential applications of molecularly imprinted fluorescent sensors.
研究领域:
环境科学
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分析化学
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纳米技术
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2022
·
IF 8.101
Shuhui Liu,Zhangshan Gao,Wanqiu He,Yuting Wu,Jiwen Liu,Shuo Zhang,Liping Yan,Shengyong Mao,Xizhi Shi,Wentao Fan,Suquan Song
Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most common chronic liver disorders in the world, and yet has no approved pharmacotherapy due to the etiology is complex. In the last ten years, increasing evidence have identified the environmental pollutants as risk factors for MAFLD. However, the underlying mechanism remains unclear. Our study found that bromoacetic acid (BAA, a typical kind of environmental toxin) increased triglycerides and total cholesterol levels as well as induced obvious hepatic steatosis and inflammation. The lipidomics showed that ferroptosis was implicated in the environmental toxin–linked MAFLD. Besides, the analysis of microbial metabolomics showed significant change of gut microbiome in BAA groups and the content of gut microbiota metabolite (glycochenodeoxycholate, GCDCA) increased sharply. In vitro study, we observed features of ferroptotic cells by transmission electron microscopy after BAA/GCDCA treatment . Besides, we demonstrated that BAA/GCDCA significantly increased iron contents, with upregulating transferrin receptor (TFR) and acyl-CoA synthetase long-chain family 4 (ACSL4) expression levels. By contrast, iron chelator or silencing TFR relieved BAA/GCDCA-induced lipid metabolism disorder and inflammation. What's more, the interaction between TFR and ACSL4 was also identified. Taken together, we found that, in response to environmental toxin , gut microbiota metabolite GCDCA activates TFR-ACSL4-mediated ferroptosis, which triggered subsequent lipid metabolism disorder and inflammation. Moreover, these findings firstly highlighted the functional relevance among ferroptosis, lipid metabolism and gut microbiota metabolite during environmental pollutant exposure, which shed light on the deep mechanism of environmental toxin-related MAFLD, providing potential targets for the prevention of MAFLD.
研究领域:
肝病学
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毒理学
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微生物学
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代谢组学
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脂质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）