Particle and Fibre Toxicology最新文献

{"title":"Combustion products of burn pit constituents induce more changes in asthmatic than non-asthmatic murine lungs.","authors":"Lanazha Belfield-Simpson, Jessica R Martin, Matthew K McPeek, Alessandra Livraghi-Butrico, Hong Dang, Yong Ho Kim, M Ian Gilmour, Claire M Doerschuk","doi":"10.1186/s12989-025-00625-w","DOIUrl":"10.1186/s12989-025-00625-w","url":null,"abstract":"<p><strong>Background: </strong>Burn pits, a method for disposal of military waste outside the United States, produce toxic substances, to which 3.5 million military personnel have been and continue to be exposed. Mild asthma (persistent or intermittent symptoms of asthma but no change in pulmonary function tests) is found among military personnel. We investigated whether burn pit combustion products (CPs) are more detrimental to the airways of asthmatic than non-asthmatic mice.</p><p><strong>Methods: </strong>Mice were exposed to house dust mite antigen (HDM) or phosphate-buffered saline (PBS) 5 times over 2 weeks to initiate asthma-like airway injury. Condensates of CPs or saline were generated by flaming combustion of military cardboard, plastic and military plywood. CPs were aspirated oropharyngeally at 24 h after the final HDM or PBS instillation. The lungs were studied 24 h later.</p><p><strong>Results: </strong>HDM increased recruitment of eosinophils and mucus projection, both Muc5ac and Muc5b mRNAs and protein. Following exposure to CPs, mice exposed to HDM had a greater inflammatory response and injury, as measured by increased neutrophil recruitment and the concentration of protein in the bronchoalveolar lavage (BAL), than control mice exposed to PBS. Expression of neutrophil chemokines was enhanced. CPs had no effect on HDM-induced eosinophil recruitment or expression of Th2 cytokines. CPs had no effect on mucus production in PBS or HDM mice. However, CPs increased intraluminal mucus, as revealed by AB-PAS staining, only in HDM mice, suggesting that CPs impaired mucociliary clearance (MCC), the lung's primary defense system, only in asthmatic airways. Lung RNA sequencing revealed that CPs increased genes and gene pathways describing inflammatory processes and impaired structure and function of cilia to a greater degree in HDM mice.</p><p><strong>Conclusions: </strong>These data indicate that asthmatic mice are more susceptible to CP-induced lung remodeling and dysfunction than non-asthmatic mice. Enhanced chemokine expression suggests that the CXCL1,2,5/CXCR2 axis may be the mechanism of the increased neutrophil recruitment. A potential mechanism of mucus accumulation is that inhalation of CPs amplifies the changes in cilia and MCC caused by asthma and triggers a positive feedback loop of enhanced inflammation induced by this accumulating mucus.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"21"},"PeriodicalIF":8.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to ambient air pollution over developmental stages induced neurodevelopmental impairment in mice offspring via microbiome-gut-brain axis.","authors":"Zijun Yang, Yi Zhang, Shanshan Ran, Jingyi Zhang, Yonggui Gao, Yali Zhang, Xinyue Li, Baozhuo Ai, Shengtao Wei, Fei Tian, Guang Jia, Hualiang Lin, Zhangjian Chen, Zilong Zhang","doi":"10.1186/s12989-025-00637-6","DOIUrl":"10.1186/s12989-025-00637-6","url":null,"abstract":"<p><p>Exposure to air pollution has been increasingly recognized as a risk factor for neurodevelopmental disorders, and gut microbiome may play a critical role. However, current evidence still remains scarce. In the present study, mice were exposed to real-time ambient air pollution from conception through young adulthood, with neurobehavioral performance and gut microbiome being assessed across different developmental stages. Neurodevelopmental changes including emotional and cognitive impairments were observed in behavioral tests, accompanied by pathological and inflammation changes in brain, which were more pronounced in adolescence than in young adulthood. Alterations in the compositions and functions of gut microbiome were also revealed by fecal metagenomic sequencing. Mediation analysis showed that gut microbiome alterations significantly contributed to the observed neurodevelopmental changes induced by air pollution. Furthermore, after antibiotic (ABX) intervention, the observed neurobehavioral, pathological and inflammatory differences between the exposed and control groups diminished. These findings indicate that the gut microbiome mediates the neurodevelopmental damage caused by exposure to air pollution during developmental stages, adding novel insights on the underlying mechanisms linking air pollution and neurodevelopmental disorders.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"20"},"PeriodicalIF":7.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopersistence of man-made vitreous fibres (MMVF) / synthetic vitreous fibres (SVF): advancing from animal models to acellular testing.","authors":"Craig A Poland, Léa Hiéronimus, Denis V Okhrimenko, John W Hoffman","doi":"10.1186/s12989-025-00636-7","DOIUrl":"10.1186/s12989-025-00636-7","url":null,"abstract":"<p><p>The field of fibre toxicology highlights a significant connection between the physicochemical properties of fibres-such as diameter, length, and durability-and their toxicity when inhaled. Among these properties, durability, particularly in terms of biopersistence and retention time in the lungs, is crucial in determining chronic toxicity. This understanding of fibre biopersistence is especially relevant to the regulation and safety assessment of Man-Made Vitreous Fibres (MMVF), also referred to in North American literature as Synthetic Vitreous Fibres (SVF). Despite its importance, current practices rely heavily on in vivo testing methods for evaluating biopersistence, which conflicts with the movement towards reducing animal testing and utilising new approach methodologies (NAMs) for hazard and risk assessment. In vitro assessments of biodurability have long been employed by the research community and industry alike to investigate the persistence of fibres in the lung, offering an alternative to reduce animal testing to evaluate this critical mediator of fibre toxicity. Here, we explore recent developments in acellular in vitro biodurability approaches for assessing fibre durability in the lung, addressing the variations and key challenges associated with using these methods to determine the safety of bio-soluble MMVF.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"19"},"PeriodicalIF":7.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of subway air particles on healthy adults: a randomized controlled trial in a Chinese city.","authors":"Yuan Sun, Yuting Xiang, Yuwei Chen, Dan Xu, Tianyun Wang, Fanmei Zeng, Yu Bao, Luwei Zhao, Yifei Li, Qing Xia, Ye Deng, Jiamei Chen, Yuting Wang, Wen Peng, Guanhua Pang, Miao He","doi":"10.1186/s12989-025-00638-5","DOIUrl":"10.1186/s12989-025-00638-5","url":null,"abstract":"<p><strong>Background: </strong>Subway systems reduce traffic congestion, air pollution, and carbon dioxide emissions in cities but the impacts of subway air pollution on the health of subway users remain obscure. We conducted a randomized controlled trial involving 83 healthy adults, with 80 included in the final analysis, randomly grouped to spend 2 h daily for 5 consecutive days either in an office or on a subway platform. The fine (PM_2.5) and thoracic (PM₁₀) particles concentrations, temperature, and humidity were monitored. Measurements of health parameters were assessed, including lung function and levels of fractional exhaled nitric oxide (FeNO), inflammatory and oxidative stress biomarkers, and metabolites in serum.</p><p><strong>Results: </strong>The subway platform exhibited significantly high pollutant levels, with mean PM_2.5 and PM₁₀ concentrations of 193.4 ± 39.4 µg/m³ and 311.5 ± 64.3 µg/m³ respectively. After the 5-day subway exposure, significant declines were observed in lung-function index values, including forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC), maximal voluntary ventilation (MVV) and peak expiratory flow rate (PEFR) as well as serum levels of glutathione peroxidase (GPX)-1 (p < 0.05). Conversely, somatosensory symptom scores, FeNO levels, and serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-8 were strongly elevated (p < 0.05). Results indicated increased arsenic and cobalt and decreased selenium in urine after the subway exposure (p < 0.05). Finally, the subway exposure was associated with disruptions in seven metabolic pathways and nine metabolites, particularly the depletion of L-cysteine, pretyrosine and O-acetyl-L-serine.</p><p><strong>Conclusions: </strong>This study provides the first evidence that repeated exposure to subway airborne particles is associated with reduced lung function and increased respiratory and systemic inflammation in healthy adults. Our results underscore the need to develop strategies to mitigate exposure risks, ultimately protecting public health in urban environments.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"18"},"PeriodicalIF":8.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of environmental microplastic exposure on HepG2 cells: unraveling proliferation, mitochondrial dynamics and autophagy activation.","authors":"Hana Najahi, Nicola Alessio, Massimo Venditti, Ida Lettiero, Domenico Aprile, Gea Oliveri Conti, Tiziana Cappello, Giovanni Di Bernardo, Umberto Galderisi, Sergio Minucci, Margherita Ferrante, Mohamed Banni","doi":"10.1186/s12989-025-00632-x","DOIUrl":"10.1186/s12989-025-00632-x","url":null,"abstract":"<p><p>The rise of microplastic (MPs) pollution presents a pressing environmental issue, raising concerns about its potential health impacts on human populations. Given the critical role of the liver in detoxification and metabolism, understanding the effects of MPs on the human hepatoma cell line HepG2 cells is essential for comprehensively assessing the dangers associated with MPs pollution to human health. Until now, the assessment of the harmful impact of polyethylene (PE) and polyethylene terephthalate (PET) on HepG2 has been incomplete and lacks certain essential data points. In this particular setting, we examined parameters such as cell viability, oxidative stress, mtDNA integrity, mitochondrial membrane potential, and autophagy in HepG2 cells exposed for 72 h to PET and PE at a concentration of 10 µg/mL. Our data revealed that exposure of HepG2 to MPs causes an increase in cell viability accompanied by a heightened ROS and altered mitochondrial function, as revealed by decreased mtDNA integrity and membrane potential. In addition, results demonstrated that exposure to PET and PE activated autophagic events, as suggested by the increased levels of the specific markers LC3 and p62. This last point was further confirmed using bafilomycin, a specific blocker that hinders the merging of autophagosomes and lysosomes, thereby blocking autophagic degradation processes. Given the increasing evidence of food chain MPs contamination and its possible harmful effects, our data should be carefully considered.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"17"},"PeriodicalIF":7.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune consequences of exposure to β-pinene oxidation aerosols: adult versus gestational murine models.","authors":"Muriel Pichavant, Madjid Djouina, Gwenola Kervoaze, Christophe Waxin, Nicolas Houzel, Emeline Driencourt, Cécile Thiry, Cécile Vignal, Cécile Coeur, Mathilde Body-Malapel","doi":"10.1186/s12989-025-00631-y","DOIUrl":"10.1186/s12989-025-00631-y","url":null,"abstract":"<p><strong>Background: </strong>While studies demonstrating the adverse effects of air pollution on human health are accumulating, studies on secondary organic aerosol (SOA) are scarce. However, SOA accounts for a significant portion of airborne particulate matter. In particular, pinene biogenic SOA contributes predominantly to SOA loading in the outdoor atmosphere of natural and urban areas and are also emitted indoors because of the presence of terpenes in numerous consumer products. Our aim was to study the immune consequences of acute exposure to β-pinene ozonolysis gaseous and SOA products in mice. This reaction was generated in an atmospheric simulation chamber, and the mice were exposed to the particulate and gaseous products, to the gaseous products only, or to synthetic air 2 h per day for 3 days in real time in a whole-body inhalation chamber. Exposures were performed in adulthood or in utero. Since some adverse effects only occur in individuals weakened by existing immune activation, such as low-grade inflammation, the immune response was measured in the steady state or in a state of moderate systemic inflammation induced by lipopolysaccharide administration.</p><p><strong>Results: </strong>Exposure of healthy adult mice caused minor immunosuppression in the lungs. However, in adult mice weakened by moderate systemic inflammation, the same exposure conditions revealed that mice exposed to the β-pinene ozonolysis particulate and gaseous products presented deficient pulmonary and systemic immune responses, including excessive recruitment of B lymphocytes, CD4⁺ T lymphocytes, CD11b⁺ dendritic cells, inflammatory monocytes and neutrophils in the lungs and defective recruitment of regulatory T cells in the spleen. In offspring exposed to β-pinene ozonolysis products in utero, the LPS-induced upregulation of Ccl2, Cxcl10 and Icam1 mRNA levels in the lungs and the activation of dendritic cells in the spleen were excessive in female mice. The male offspring developed a normal response to moderate systemic inflammation, except for impaired activation of CD4⁺ T cells and increased activation of CD103⁺ dendritic cells in the spleen.</p><p><strong>Conclusion: </strong>In mice, pulmonary and systemic immune reactions in response to moderate systemic inflammation are dysregulated by exposure to common secondary oxidation products, highlighting interest in the role of these neglected atmospheric compounds in immune disease development and susceptibility to infections.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"16"},"PeriodicalIF":7.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hazard screening of colloidal silica nanomaterials with varying degrees of silane surface functionalization: a safe-by-design case study.","authors":"Nienke Ruijter, Ilaria Zanoni, Daniel Persson, Josje Arts, Marie Carriere, Arnaud Guiot, Michael Persson, Alberto Katsumiti, Jessica Marshall, Matthew Boyles, Flemming R Cassee, Hedwig Braakhuis","doi":"10.1186/s12989-025-00629-6","DOIUrl":"10.1186/s12989-025-00629-6","url":null,"abstract":"<p><strong>Background: </strong>The Safe and Sustainable by Design (SSbD) concept facilitates the design of safer and more sustainable chemicals and materials and is a crucial approach towards reaching the goals set out in the European Green Deal. It is critical that suitable guidance is provided on how to use new approach methodologies (NAMs) to fill hazard data gaps for nanomaterials (NMs) to facilitate SSbD decisions. Here, we showcase a nano-specific in vitro SSbD case study. The five colloidal silica nanoforms (SiO₂-NFs) under investigation in this study are surface modified with varying amounts of glycerolpropyl-organosilane groups. In this study, we use a simple yet comprehensive in vitro test battery along with thorough particle characterization to investigate the effect of surface silanization on in vitro toxicity to inform SSbD decisions.</p><p><strong>Results: </strong>Cytotoxic, pro-inflammatory and oxidative stress responses in A549, dTHP-1, and BEAS-2B cells after exposure to SiO₂-NFs submerged and at the air-liquid interface (ALI) decreased with increasing silane surface modification. None of the SiO₂-NFs showed surface reactivity or haemolytic potential. Deposition assessment using inductively coupled plasma - optical emission spectrometry (ICP-OES) revealed that increasing silane surface modification decreased particle settling. The two SiO₂-NFs with the highest amount of surface silanization did not reach the cells in a submerged exposure setting, and they were therefore only tested at the ALI. Identical dose-response curves were observed for both the submerged testing and testing at the ALI for the SiO₂-NFs without and with low/intermediate surface functionalization, again showing a decrease in effects with increasing surface functionalization.</p><p><strong>Conclusion: </strong>We show that in vitro toxicity assays provide valuable information for SSbD decision making. In vitro cytotoxic, pro-inflammatory and oxidative stress responses can be reduced with increasing surface silane functionalization. The reduced deposition efficiency with increasing silane functionalization, however, highlights that thorough characterization of particle behaviour in cell culture medium should always be performed for SSbD hazard testing. The amount of silane required to reduce toxicity is important information for the future production of safer SiO₂-NFs and nano-enabled products. Exposure, functionality, and sustainability remain to be investigated to draw full SSbD conclusions.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"15"},"PeriodicalIF":7.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute health effects of ambient air pollution including ultrafine particles in a semi-experimental setting in young, healthy individuals.","authors":"Elisabeth Folwarczny, Felix Forster, Rudolf A Jörres, Stefan Rakete, Sheng Ye, Mark Wenig, Nadine Gawlitta, Jürgen Schnelle-Kreis, Richard Winterhalter, Alexander Müller, Dennis Nowak, Stefan Karrasch","doi":"10.1186/s12989-025-00628-7","DOIUrl":"10.1186/s12989-025-00628-7","url":null,"abstract":"<p><strong>Background: </strong>Multiple effects of ultrafine particles (UFP) on human subjects are known but there is less knowledge of how relative exposure levels between ultrafine and fine particles as typically encountered in large cities affect lung function and cardiovascular parameters.</p><p><strong>Methods: </strong>Four sites with high/low levels of ultrafine particles and/or fine particles were selected in the city of Munich, Germany: control area (woodland), urban environment, heavy traffic site, biomass combustion (beech wood). In a randomized cross-over design, 26 young, healthy individuals were exposed at each site over 75 min to atmospheric pollutants, which were monitored continuously, while performing intermittent (5 min per 15 min) light exercise. Parameters assessed pre and post exposure comprised symptoms, spirometry, lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), alveolar volume (AV), the fractional concentration of exhaled nitric oxide (FeNO), reactive hyperemia index (RHI), blood pressure, and heart rate. Outcomes were expressed as percent changes of parameters and analyses performed by either comparing the four sites or by multiple linear regression analyses using the measured pollutant levels.</p><p><strong>Results: </strong>The sites showed the planned pattern of exposure levels but with large overlap. Outcomes showed no statistically significant differences between sites, except for symptoms which were elevated with heavy traffic site exposure and biomass combustion. In regression analyses, AV decreased by 0.92 (95% confidence interval (CI): 0.28 to 1.57) % per 10,000/cm³ UFP; similarly, for LDSA (lung-deposited surface area), which was highly correlated with UFP. Overall, FeNO slightly increased after exposure, but this increase was attenuated by 5.4 (95% CI: 1.8 to 9.2) % per 10 ppb ambient NO₂. Heart rate decreased after exposures overall; this decrease was enhanced by 2.1 (95% CI: 0.3 to 4.0) % per 10,000/cm³ UFP.</p><p><strong>Conclusions: </strong>Short-term exposures to UFP elicited a reduction in the lung volume (AV) accessible to gas transport by diffusion and convection. FeNO was slightly elevated after all exposures, but this increase was significantly smaller at higher ambient NO₂ concentrations. While these effects were too small to be clinically relevant, they demonstrated that typical levels of urban air pollution had measurable acute effects in young, healthy individuals.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"14"},"PeriodicalIF":7.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene nanoplastics exposure induces cognitive impairment in mice via induction of oxidative stress and ERK/MAPK-mediated neuronal cuproptosis.","authors":"Yinuo Chen, Yiyang Nan, Lang Xu, Anqi Dai, Rosa Maria Martinez Orteg, Mantong Ma, Yan Zeng, Jinquan Li","doi":"10.1186/s12989-025-00633-w","DOIUrl":"10.1186/s12989-025-00633-w","url":null,"abstract":"<p><strong>Background: </strong>Recent studies emphasize the significance of copper dyshomeostasis in neurodegenerative diseases, such as Alzheimer's and Parkinson's, thereby highlighting the role of copper in neurotoxicity. Cuproptosis, a novel mechanism of copper-dependent cell death, remains underexplored, particularly concerning environmental pollutants like polystyrene nanoplastics (PS-NPs). While PS-NPs are recognized for inducing neurotoxicity through various forms of cell death, including apoptosis and ferroptosis, their potential to trigger neuronal cuproptosis has not yet been investigated. This study aims to determine whether exposure to PS-NPs induces neurotoxicity via cuproptosis and to explore the preliminary molecular mechanisms involved, thereby addressing this significant knowledge gap.</p><p><strong>Methods: </strong>Seven-week-old male C57BL/6 mice were exposed to PS-NPs at dose of 12.5 mg/kg, and were co-treated with the antioxidant N-acetylcysteine (NAC). Complementary in vitro experiments were conducted using SH-SY5Y neuronal cells exposed to PS-NPs at a concentration of 0.75 mg/mL, with interventions that included the copper chelator tetrathiomolybdate (TTM), NAC, and the MAPK inhibitor PD98059.</p><p><strong>Results: </strong>Exposure to PS-NPs significantly increased cerebral copper accumulation (P < 0.05) and induced cuproptosis, characterized by lipid-acylated DLAT oligomerization, dysregulation of cuproptosis regulators (FDX1, LIAS, HSP70), and mitochondrial damage. In murine models, PS-NPs elicited neurotoxicity, as evidenced by neuronal loss, decreased Nissl body density, impaired synaptic plasticity, and suppressed oxidative stress markers (GSH, SOD, Nrf2), alongside activation of the ERK-MAPK pathway, ultimately resulting in deficits in learning and memory. Treatment with NAC alleviated these adverse effects. In SH-SY5Y cells, exposure to PS-NPs resulted in reduced cell viability (p < 0.01), an effect that was mitigated by TTM. Furthermore, NAC and PD98059 were found to reverse elevated copper levels, cuproptosis markers, and mitochondrial anomalies (p < 0.05).</p><p><strong>Conclusion: </strong>This study presents preliminary evidence indicating that PS-NPs may induce neuronal cuproptosis, potentially through the oxidative stress-mediated activation of the ERK-MAPK pathway, which contributes to cognitive dysfunction in mice. These findings provide insights into the potential mechanisms underlying PS-NPs neurotoxicity and highlight possible therapeutic targets, such as copper chelation or MAPK inhibition, for mitigating the neurological risks associated with nanoplastic exposure, pending further validation in human-relevant models.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"13"},"PeriodicalIF":7.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Central IKKβ Inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes.","authors":"Cuiqing Liu, Laura K Fonken, Aixia Wang, Andrei Maiseyeu, Yuntao Bai, Tse-Yao Wang, Santosh Maurya, Yi-An Ko, Muthu Periasamy, Timothy Dvonch, Masako Morishita, Robert D Brook, Jack Harkema, Zhekang Ying, Bhramar Mukherjee, Qinghua Sun, Randy J Nelson, Sanjay Rajagopalan","doi":"10.1186/s12989-025-00630-z","DOIUrl":"10.1186/s12989-025-00630-z","url":null,"abstract":"","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"12"},"PeriodicalIF":7.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}