Particle and Fibre Toxicology最新文献

{"title":"Emerging cardiovascular risks of micro- and nanoplastics: toxic effects and mechanistic pathways.","authors":"Gang Liu, Qiuya Cai, Tingchen Qin, Xiatian Yu, Binbin Pan, Lin Ye, Lisha Jia, Xianwei Wang","doi":"10.1186/s12989-026-00669-6","DOIUrl":"10.1186/s12989-026-00669-6","url":null,"abstract":"<p><p>Micro- and nanoplastics (MNPs), due to their widespread distribution and chemical stability, have emerged as novel environmental contaminants threatening cardiovascular health. Evidence links MNPs to conditions such as atherosclerosis, cardiac fibrosis, myocardial infarction, and other cardiovascular diseases (CVDs). Recently, MNPs have been found within atherosclerotic plaques and in the myocardial tissues of surgery patients, highlighting their close association with cardiovascular pathology. Investigations have demonstrated that MNPs can enter the human body through oral ingestion, inhalation, dermal contact, and medical procedures, and subsequently accumulate in the blood, blood vessels, and cardiac tissues. Once deposited, these particles induce oxidative and endoplasmic reticulum stress, disrupt mitochondrial function, and activate inflammatory signaling pathways, ultimately triggering cell death. These processes contribute to endothelial dysfunction, cardiac damage and fibrosis, vascular smooth muscle cell phenotypic switching, and macrophage foam cell formation, thereby likely contributing to the onset and progression of CVDs. Despite these findings, the potential cardiovascular risks of MNPs and the underlying mechanisms remain largely unexplored. This review summarizes the basic properties of MNPs, their biodistribution within the cardiovascular system, toxic effects, and underlying molecular mechanisms, providing a foundation for future risk assessment and the development of preventive strategies.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13001288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321856","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":"Gut-ovary axis mediated synergistic reproductive toxicity of polystyrene nanoplastics and perfluorobutanoic acid co-exposure: pyroptotic signaling and probiotic mitigation.","authors":"Jialyu Huang, Yiwei Zhang, Penghui Nie, Qimei Luo, Rili Hu, Ruiying Zhang, Yan Zhao, Maolin Yu, Hengyi Xu","doi":"10.1186/s12989-026-00667-8","DOIUrl":"10.1186/s12989-026-00667-8","url":null,"abstract":"<p><p>Polystyrene nanoplastics (PS-NPLs) and perfluorobutanoic acid (PFBA) are pervasive contaminants of great concern and can enter human body primarily through gastrointestinal tract. However, their single and combined effects on female reproductive health remain poorly explored. In this study, PFBA was found to be adsorbed onto PS-NPLs through both chemical and physical interactions. Compared with single exposure, co-exposure to PS-NPLs (0.04 mg/d) and PFBA (0.28 mg/d) for 28 days caused more severe ovarian toxicity in rats, as evidenced by decreased primordial follicles, increased follicular atresia, and sex hormone abnormalities. Mechanistically, the co-exposure was associated with the gut barrier damage and elevated levels of lipopolysaccharide in the bloodstream, concomitant with altered redox homeostasis, inflammation and NLRP3/caspase-1-related pyroptosis of the ovary. Moreover, supplementation with probiotic Lactiplantibacillus plantarum P101 partially attenuated ovarian injury via modulating gut microbiota and mitigating the above process. Taken together, our study revealed a synergistic impact of PS-NPLs and PFBA on female reproduction, uncovered the underlying mechanisms from the perspective of gut-ovary axis, and provided valuable insights into potential preventive strategies.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776549","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":"A comparative biodistribution and toxicity study of single and multi-component nanomaterials: NMs: TiO₂, SiC, and SiC@TiO₂.","authors":"Wenting Zhang, Muhammad Daniyal Ghouri, Magda Blosi, Ying Liu, Chunying Chen, Flemming R Cassee, Rong Cai","doi":"10.1186/s12989-026-00664-x","DOIUrl":"10.1186/s12989-026-00664-x","url":null,"abstract":"<p><p>BACKGROUND: With the increasing integration of nanomaterials (NMs) into daily life, their technological advantages have become evident. However, their intricate interactions with biological systems introduce complexities that can lead to unpredictable toxicological outcomes. This study investigated the in vivo toxicokinetics and toxicodynamics of single- and multi-component NMs composed of silicon carbide (SiC), titanium dioxide (TiO2), and a SiC@TiO2 composite, along with a physical mixture of SiC and TiO2 in the same ratio as the composite. Rats were exposed to these materials via single intratracheal instillation, and biological responses were assessed over time (1 h to 28 days) to identify the no-observed-adverse-effect level (NOAEL). RESULTS: All NMs induced minimal structural alterations in lung tissue and prompted varying degrees of inflammatory cell infiltration. Over time, translocation from the lungs to secondary organs (heart, spleen, liver, kidney) was observed, with distinct distribution patterns between Si- and Ti-containing NMs. Bronchoalveolar lavage fluid analysis revealed a minimal to mild inflammatory response that evolved in a time-dependent manner, even at NOAEL exposure levels, suggesting delayed-onset biological effects. CONCLUSIONS: SiC@TiO2 demonstrated a reduced pulmonary toxicological profile relative to its single-component counterparts, likely due to antagonistic effects between its constituents. These findings highlight the need to assess multicomponent nanomaterials as distinct entities and suggest that rational material design may help mitigate adverse biological effects, supporting safer nanotechnology development. </p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228069","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":"Alignment of in vitro and in vivo pulmonary inflammation models using crystalline quartz silica.","authors":"Isidora Loncarevic, Seyran Mutlu, Martina Dzepic, Sandeep Keshavan, Sandor Balog, Alke Petri-Fink, Fabian Blank, Barbara Rothen-Rutishauser","doi":"10.1186/s12989-026-00665-w","DOIUrl":"10.1186/s12989-026-00665-w","url":null,"abstract":"<p><strong>Background: </strong>Systematic in vitro-in vivo comparisons are increasingly used to assess the relevance and predictivity of in vitro lung models for inhalation toxicology and regulatory risk assessment. Here, we compared inflammatory endpoints across established in vitro and in vivo pulmonary models following exposure to crystalline quartz silica particles (DQ₁₂). To better align exposure timelines, in vitro responses assessed at 24 h were extended to 7 days, matching the post-exposure period recommended in OECD inhalation testing guidelines for animal testing. To test its potential and limitations, we utilized a harmonized in vitro co-culture model consisting of the human bronchial cell line Calu-3 and human monocyte-derived macrophages, which were exposed to DQ₁₂ particles.</p><p><strong>Results: </strong>No increased cytotoxicity or impairment of barrier integrity, as assessed by transepithelial electrical resistance (TEER) and tight junction protein 1 (TJP1) gene expression, was observed 7 days after exposure in vitro, in contrast to clear tissue damage detected in vivo. However, we observed increased release of interleukin (IL)-6 and IL-8, measured at both protein and gene levels. Gene expressions of IL-1β, IL-6, and IL-8 showed positive correlations between the in vitro and in vivo models.</p><p><strong>Conclusions: </strong>By extending exposure duration and aligning time points, this study identified inflammatory biomarkers that correlate between an in vitro lung model and in vivo data. These findings demonstrate the value of refined in vitro models for assessing particle-induced lung inflammation and support their relevance for hazard assessment.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"23 1","pages":"6"},"PeriodicalIF":10.6,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12918095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228098","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":"Supplemental exposure to polystyrene nanoplastics synergistically amplifies calcium oxalate crystal-induced injury to renal tubular epithelium, accelerating the formation of calcium oxalate kidney stones.","authors":"Xiaozhe Su, Yijun Yang, Heng Xiang, Caitao Dong, MingCheng Shi, Yufei Wang, Qixuan Zhou, Qianlin Song, Ziqi He, Qinhong Jiang, Bobo Chen, Yunhan Wang, Yunhe Xiong, Sixing Yang","doi":"10.1186/s12989-026-00661-0","DOIUrl":"10.1186/s12989-026-00661-0","url":null,"abstract":"<p><strong>Background: </strong>With the escalating issue of polystyrene microplastic pollution, microplastic particles have been detected in human urine. While calcium oxalate (CaOx) crystals are well-established mediators of renal stone formation, the role of microplastics, particularly polystyrene nanoplastics (PS-NPs), in promoting CaOx kidney stone formation remains unclear. This study aims to explore whether PS-NPs interact with CaOx crystals to enhance renal tubular epithelial cell injury and facilitate the formation of kidney stones.</p><p><strong>Methods: </strong>Clinical CaOx kidney stone samples were analyzed using pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS), which detected microplastic components. In vitro, human renal proximal tubular epithelial cells (HK-2) were exposed to calcium oxalate monohydrate crystals (1.5 mM), or cells were pretreated with PS-NPs (100 nm, 0.1 mg/mL) for 24 h, followed by the addition of 1.5 mM CaOx for co-treatment. Comprehensive mechanistic assessments, including whole-transcriptome RNA sequencing, crystal adhesion assays, macrophage chemotaxis and polarization analysis, ferroptosis biomarker quantification, lipid peroxidation measurement, and mitochondrial ferrous ion accumulation, were conducted. In vivo, a rat model of CaOx nephrolithiasis was induced by ethylene glycol (EG) with concurrent exposure to PS-NPs (4 mg/Kg·Day) via drinking water.</p><p><strong>Results: </strong>Clinical analysis confirmed the presence of PS-NPs and other microplastics in human CaOx kidney stones. In vitro, exposure to PS-NPs significantly altered the morphology of CaOx crystals, promoting aggregation and enhancing adhesion to renal tubular epithelial cells. Combined exposure to PS-NPs and CaOx crystals exacerbated HK-2 cell injury through upregulation of VCAM1, CXCL8-driven macrophage chemotaxis and M1 polarization, and ferroptosis induced by xCT/GPX4 suppression. Transcriptomic analysis revealed LRP6 downregulation as a central regulator in these pathological processes. Overexpression of low-density lipoprotein receptor-related protein 6 (LRP6) alleviated cell damage and attenuated inflammatory responses. In vivo, PS-NPs co-exposure exacerbated renal CaOx deposition, ferroptosis in renal tubular epithelial cells, and inflammatory responses in the rat model.</p><p><strong>Conclusion: </strong>Our study identifies PS-NPs as novel lithogenic cofactors that promote CaOx nucleation, enhance crystal adhesion to renal tubular epithelial cells, and amplify inflammation and ferroptosis through LRP6 downregulation. This suggests that microplastic pollution may be an emerging environmental risk factor for kidney stone pathogenesis.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12937549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181417","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":"Susceptibility to systemic autoimmunity rather than the presence of the HLA-DR4 peptide binding domain alone leads to severe inflammatory arthritis following inhalation of crystalline silica.","authors":"Lisa M F Janssen, Caroline de Ocampo, Dwight H Kono, Steven Ronsmans, Manosij Ghosh, Peter H M Hoet, K Michael Pollard, Jessica M Mayeux","doi":"10.1186/s12989-026-00662-z","DOIUrl":"10.1186/s12989-026-00662-z","url":null,"abstract":"<p><strong>Background: </strong>The mucosal origins hypothesis of rheumatoid arthritis (RA) posits that inhalant exposures, such as cigarette smoke and crystalline silica (c-silica), trigger immune responses in the lungs that contribute to joint disease onset. However, the relationship between inhalants, lung inflammation, and inflammatory arthritis remains poorly understood.</p><p><strong>Results: </strong>This study compared the development of inflammatory arthritis in two genetically susceptible mouse strains, the BXD2/TyJ (BXD2) and chimeric HLA-DR4-IE transgenic (DR4-Tg), following delivery of c-silica to the lungs via oropharyngeal aspiration. In BXD2 mice, c-silica exposure was associated with rapid arthritis development, marked by synovial cell hyperplasia, pannus formation, and severe erosion of cartilage and bone. These features were preceded by pulmonary inflammation characterized by lymphoid-like cell clusters lining vessels and bronchi which cell-specific immunofluorescent microscopy identified as organized lymphoid structures consistent with inducible bronchus-associated lymphoid tissue (iBALT). Inflammatory arthritis was also preceded by autoantibodies associated with RA and other systemic autoimmune diseases including anti-citrullinated protein autoantibodies (ACPA) and rheumatoid factor (RF) in bronchoalveolar lavage fluid (BALF). However, the most predominant autoantibodies in BALF were against extractable nuclear antigens (ENA). Anti-ENA were also prominent in serum and microarray autoantigen analysis confirmed the response as targeting components of Sm and RNP small nuclear ribonucleoproteins (snRNPs). In contrast, DR4-Tg mice had no signs of arthritis, milder lung inflammation lacking iBALT, and negligible autoantibody responses.</p><p><strong>Conclusion: </strong>Genetic predisposition beyond HLA-DR4 alone is required for the immunological manifestations that lead to c-silica mediated inflammatory arthritis. These findings provide novel insights into the relationship between mucosal exposure and RA pathogenesis.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143147","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 carbon-based fibers morphologies on their carcinogenic potential.","authors":"Anna Wagner, Florian Schulz, Asmus Meyer-Plath, Franziska Dahlmann, Susanne Rittinghausen, Dirk Schaudien","doi":"10.1186/s12989-026-00663-y","DOIUrl":"10.1186/s12989-026-00663-y","url":null,"abstract":"<p><strong>Background: </strong>Carbon based fibers are considered to exhibit a carcinogenic potency when inhaled into the deep lung. Mesotheliomas develop after intraperitoneal application of multi-walled carbon nanotubes (MWCNTs) exceeding a diameter of about 37 nm, whereas carcinogenic potency decreases for diameters below this threshold. While large MWCNT diameters are associated with a rigid fiber geometry, this study examined the effects of MWCNTs with smaller diameters ranging from 10 to 30 nm. Also, a sample of single-walled carbon nanotubes (SWCNTs) exhibiting single fiber diameters significantly below 10 nm and showing a flexible geometry was included since individual SWCNT fibers can aggregate to form bundles that exhibit increased rigidity. Additionally, the carcinogenic effect of pitch-based carbon fiber fragments was investigated. Carbon fibers are industrially produced with diameters larger than 4 µm and are thus not per se respirable. However, pitch-based fibers tend to break along their longitudinal axis, resulting in respirable fragments, partially of critical WHO dimensions. Four CNT samples with a geometric mean diameter (GMD) of 30 nm, 20 nm, 10 nm, and smaller than 10 nm, as well as one fragmented carbon fiber sample (GMD 1.3 µm) were intraperitoneally injected into rats in two dosages (0.1 × 10⁹ and 1 × 10⁹ WHO fibers or WHO-analog nanofibers) and observed for up to 24 months. A long amosite asbestos (GMD 0.37 µm) with known fiber-specific carcinogenic effect served as a positive control (0.1 × 10⁹ WHO fibers).</p><p><strong>Results: </strong>A small number of mesotheliomas occurred in all fiber types, but not at all dosages. For the carbon fiber material, a possible weak carcinogenic potency is seen at the higher dosage. For the SWCNT fiber, low number of mesotheliomas likewise suggest a weak carcinogenic potency. In the case of the MWCNT fiber with a GMD of 30 nm, very low number of mesotheliomas indicate a possible very weak carcinogenic potency. No clear carcinogenic potency was observed for the MWCNTs with GMDs of 20 nm and 10 nm.</p><p><strong>Conclusions: </strong>Carbon fiber fragments and thin but bundled MWCNTs showed weak carcinogenic potency. Non-bundled MWCNTs with a diameter below 30 nm did not show clearcarcinogenic potency at a dose up to 1 × 10⁹ WHO-analog nanofibers.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137678","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":"Lung retention, distribution and persistence of polymer particles in rats exposed via inhalation.","authors":"Emanoela Thá, Lan Ma-Hock, Markus Rueckel, Till Gruendling, Wendel Wohlleben, Bernd Reck, Robert Landsiedel","doi":"10.1186/s12989-025-00655-4","DOIUrl":"10.1186/s12989-025-00655-4","url":null,"abstract":"<p><strong>Background: </strong>Microplastics have been repeatedly detected in the human body, yet uncertainties surround their bioavailability and fate due to experimental challenges and limitations, especially regarding their nano-sized counterparts. Knowing that toxicokinetics information is essential for accurate risk assessment and management, this research aimed to (1) evaluate different sample preparation and quantification methods for nanoplastics particles in mammalian tissue, and (2) investigate the lung retention, bioavailability and fate of these particles.</p><p><strong>Methods: </strong>In this study, rats inhaled aerosols with up to 50 mg/m³ of Nile Red-labeled polystyrene (PS-NR) or unlabeled polyamide particles (PA-6) particles for 28 days. The tissues were analyzed for the presence of polymer particles. PS-NR were quantified in formalin-fixed tissue by confocal fluorescence laser microscopy with semi-automatic imaging analysis, and PA-6 particles were quantified in dried tissues by pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS).</p><p><strong>Results: </strong>PA-6 deposition was detected and quantified in lung and lymph nodes. Deposition of PS-NR was quantified in lungs and lung-draining lymph nodes, but no particles were detected in the liver, spleen, and kidneys. The lung burdens and translocation to the draining lymph nodes were similar for both particles, and particles were still detectable after the end of the exposure periods (five weeks for PS-NR and 13 weeks for PA-6).</p><p><strong>Conclusions: </strong>This work highlights limitations and applicability of the various methods for sample preparation, detecting and quantifying polymer particles in mammalian tissues. In addition, it provides reliable data on the internal dose of inhaled polymer particles.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":"2"},"PeriodicalIF":10.6,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12814592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994435","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":"Particulate matter 2.5 promotes bladder cancer cell migration and invasion through the crosstalk between integrin-mediated MAPK/ERK and Wnt/β-catenin pathways.","authors":"Yung-Ting Cheng, Kai-Hsi Lu, Shu-Ying Hong, Chung-Hsin Chen, Chao-Yuan Huang, Hsiu-Ni Kung","doi":"10.1186/s12989-025-00656-3","DOIUrl":"10.1186/s12989-025-00656-3","url":null,"abstract":"<p><strong>Background: </strong>Fine particulate matter 2.5 (PM_2.5), a key indicator of air pollution, is classified as a human carcinogen. However, the link between air pollution and bladder cancer (BC) progression remains unclear. Dysregulation of the Wingless-related integration site (Wnt)/β-catenin and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways is a key driver of tumorigenesis in multiple cancers, including BC.</p><p><strong>Results: </strong>This study demonstrated that PM_2.5 exposure enhances BC cell migration and invasion. Ribonucleic acid (RNA) sequencing identified the Wnt signaling pathway as a key regulator in PM_2.5-exposed BC cells. Elevated protein levels of Wnt3A, Wnt5A, and β-catenin, along with the nuclear translocation of β-catenin, further highlighted the role of the PM_2.5-activated Wnt/β-catenin pathway in promoting BC progression. The interaction between the Wnt/β-catenin and MAPK/ ERK pathways was examined using inhibitors and shRNAs. MEK or ERK inhibition not only suppressed PM_2.5-induced upregulation of Wnt3A, Wnt5A, and β-catenin nuclear translocation but also significantly reduced the migration and invasion of PM_2.5-exposed BC cells. Both pathways represent promising therapeutic targets, and several existing pathway-specific inhibitors may be repurposed for the future clinical management of PM_2.5-induced BC progression.</p><p><strong>Conclusions: </strong>PM_2.5 promotes BC progression through both the MAPK/ERK and Wnt/β-catenin signaling pathways. MEK/ERK inhibition suppressed PM_2.5-induced nuclear translocation of β-catenin, suggesting that the MAPK/ERK pathway functions upstream of the Wnt/β-catenin pathway. This study provides mechanistic insights into how PM_2.5 exposure drives BC progression and offers a potential foundation for developing targeted therapies for PM_2.5-associated BC.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":"4"},"PeriodicalIF":10.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989747","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":"Modulatory effects of CeO₂ nanoparticles on bleomycin-induced active pulmonary disease processes in animal and human airway epithelium models.","authors":"Chang Guo, Alison Buckley, Sarah Robertson, Adam Laycock, Xianjin Cui, Eugenia Valsami-Jones, Tim Gant, Martin O Leonard, Rachel Smith","doi":"10.1186/s12989-026-00658-9","DOIUrl":"10.1186/s12989-026-00658-9","url":null,"abstract":"<p><strong>Background: </strong>Understanding the impacts of inhaled insoluble nanomaterials as they are encountered in the environment and workplace, in injured lungs remains limited, particularly with respect to their role in the progression or mitigation of lung pathology. While some studies suggest potential protective effects of cerium(IV) oxide nanoparticles (CeO₂NPs) under certain conditions, their influence during active disease processes is unclear. This study builds on prior work to investigate the effects of CeO₂NP aerosols on bleomycin-induced pulmonary injury and active disease processes.</p><p><strong>Method: </strong>To establish conditions of active pulmonary disease processes, bleomycin was used in both animal and airway epithelium models. Male Sprague-Dawley rats were intratracheally instilled with bleomycin or saline (control) followed by nose-only inhalation exposure to CeO₂NP aerosols (diameter of ~ 43 nm) or control for 3 h per day for 4 days per week for one or two weeks. At three days postexposure, the animals were sacrificed for analysis of bronchoalveolar lavage (BAL) fluid, lung histopathology and global mRNA expression. Comparative in vitro studies were conducted to investigate biological responses at the cellular level, using 3D human small airway epithelium cultures (SmallAir™) exposed to CeO₂NP aerosols (with a diameter of ~ 86 nm) at the air-liquid-interface at deposition doses comparable to those received in vivo in the small airway.</p><p><strong>Results: </strong>In vivo, bleomycin treatment resulted in an increase in total BAL cells and fibrotic staining, and significant induction of inflammatory and oxidative stress, as shown by mRNA sequencing analysis. One week of exposure to CeO₂NPs modified these responses by attenuating fibrotic staining and reducing the expression of genes associated with lung function, inflammation and epithelial-mesenchymal transition (EMT). In vitro, CeO₂NP exposure modulated some bleomycin-induced cellular responses, although these models do not fully capture the complexity of whole body and tissue systems, highlighting limitations and considerations for future in vitro exposure studies.</p><p><strong>Conclusions: </strong>In this study, inhaled CeO₂NPs modulated lung injury responses in the context of active disease, with both potential protective effects and adverse outcomes. These findings demonstrate that the timing of CeO₂NP exposure relative to disease progression is critical and highlight the need for hazard assessment frameworks to consider context-dependent effects, particularly in the presence of pre-existing lung injury.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":"5"},"PeriodicalIF":10.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12829198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989469","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}