Particle and Fibre Toxicology最新文献

{"title":"Cell-nanoparticle stickiness and dose delivery in a multi-model in silico platform: DosiGUI.","authors":"Ermes Botte, Pietro Vagaggini, Ilaria Zanoni, Nicole Guazzelli, Lara Faccani, Davide Gardini, Anna L Costa, Arti Ahluwalia","doi":"10.1186/s12989-024-00607-4","DOIUrl":"10.1186/s12989-024-00607-4","url":null,"abstract":"<p><strong>Background: </strong>It is well-known that nanoparticles sediment, diffuse and aggregate when dispersed in a fluid. Once they approach a cell monolayer, depending on the affinity or \"stickiness\" between cells and nanoparticles, they may adsorb instantaneously, settle slowly - in a time- and concentration-dependent manner - or even encounter steric hindrance and rebound. Therefore, the dose perceived by cells in culture may not necessarily be that initially administered. Methods for quantifying delivered dose are difficult to implement, as they require precise characterization of nanoparticles and exposure scenarios, as well as complex mathematical operations to handle the equations governing the system dynamics. Here we present a pipeline and a graphical user interface, DosiGUI, for application to the accurate nano-dosimetry of engineered nanoparticles on cell monolayers, which also includes methods for determining the parameters characterising nanoparticle-cell stickiness.</p><p><strong>Results: </strong>We evaluated the stickiness for 3 industrial nanoparticles (TiO₂ - NM-105, CeO₂ - NM-212 and BaSO₄ - NM-220) administered to 3 cell lines (HepG2, A549 and Caco-2) and subsequently estimated corresponding delivered doses. Our results confirm that stickiness is a function of both nanoparticle and cell type, with the stickiest combination being BaSO₄ and Caco-2 cells. The results also underline that accurate estimations of the delivered dose cannot prescind from a rigorous evaluation of the affinity between the cell type and nanoparticle under investigation.</p><p><strong>Conclusion: </strong>Accurate nanoparticle dose estimation in vitro is crucial for in vivo extrapolation, allowing for their safe use in medical and other applications. This study provides a computational platform - DosiGUI - for more reliable dose-response characterization. It also highlights the importance of cell-nanoparticle stickiness for better risk assessment of engineered nanomaterials.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505530","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":"Controlled human exposures: a review and comparison of the health effects of diesel exhaust and wood smoke.","authors":"Erin Long, Christopher F Rider, Christopher Carlsten","doi":"10.1186/s12989-024-00603-8","DOIUrl":"10.1186/s12989-024-00603-8","url":null,"abstract":"<p><p>One of the most pressing issues in global health is air pollution. Emissions from traffic-related air pollution and biomass burning are two of the most common sources of air pollution. Diesel exhaust (DE) and wood smoke (WS) have been used as models of these pollutant sources in controlled human exposure (CHE) experiments. The aim of this review was to compare the health effects of DE and WS using results obtained from CHE studies. A total of 119 CHE-DE publications and 25 CHE-WS publications were identified for review. CHE studies of DE generally involved shorter exposure durations and lower particulate matter concentrations, and demonstrated more potent dysfunctional outcomes than CHE studies of WS. In the airways, DE induces neutrophilic inflammation and increases airway hyperresponsiveness, but the effects of WS are unclear. There is strong evidence that DE provokes systemic oxidative stress and inflammation, but less evidence exists for WS. Exposure to DE was more prothrombotic than WS. DE generally increased cardiovascular dysfunction, but limited evidence is available for WS. Substantial heterogeneity in experimental methodology limited the comparison between studies. In many areas, outcomes of WS exposures tended to trend in similar directions to those of DE, suggesting that the effects of DE exposure may be useful for inferring possible responses to WS. However, several gaps in the literature were identified, predominantly pertaining to elucidating the effects of WS exposure. Future studies should strongly consider performing head-to-head comparisons between DE and WS using a CHE design to determine the differential effects of these exposures.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505531","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":"Current understanding of the impact of United States military airborne hazards and burn pit exposures on respiratory health.","authors":"Janeen H Trembley, Paul Barach, Julie M Tomáška, Jedidah T Poole, Pamela K Ginex, Robert F Miller, Jacob B Lindheimer, Anthony M Szema, Kimberly Gandy, Trishul Siddharthan, Jason P Kirkness, Joshua P Nixon, Rosie Lopez Torres, Mark A Klein, Timothy R Nurkiewicz, Tammy A Butterick","doi":"10.1186/s12989-024-00606-5","DOIUrl":"10.1186/s12989-024-00606-5","url":null,"abstract":"<p><p>Millions of United States (U.S.) troops deployed to the Middle East and Southwest Asia were exposed to toxic airborne hazards and/or open-air burn pits. Burn pit emissions contain particulate matter combined with toxic gasses and heavy metals. Ongoing research has demonstrated that exposures to the airborne hazards from military burn pits have profound and lasting health and wellness consequences. Research on the long-term health consequences of exposure to open burn pits has been limited. Work continues to understand the scope of the health impacts and the underlying pathobiology following exposures and to establish care standards. The U.S. Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act was signed into law August 2022. This act expands the benefits and services to U.S. Veterans exposed to toxicants, requires the Veterans Health Administration to provide toxic exposure screening, and supports increased research, education, and treatment due to toxic occupational exposures. This review highlights the state of the science related to military burn pit exposures research with an emphasis on pulmonary health. Clinical data demonstrate areas of reduced or delayed pulmonary ventilation and lung pathologies such as small airways scarring, diffuse collagen deposition and focal areas of ossification. Identification and characterization of foreign matter deposition in lung tissues are reported, including particulate matter, silica, titanium oxides, and polycyclic aromatic hydrocarbons. These data are consistent with toxic exposures and with the symptoms reported by post-deployment Veterans despite near-normal non-invasive pulmonary evaluations. On-going work toward new methods for non-invasive pulmonary diagnoses and disease monitoring are described. We propose various studies and databases as resources for clinical and health outcomes research. Pre-clinical research using different burn pit modeling approaches are summarized, including oropharyngeal aspiration, intranasal inhalation, and whole-body exposure chamber inhalation. These studies focus on the impacts of specific toxic substances as well as the effects of short-term and sustained insults over time on the pulmonary systems.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472100","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":"Effects of simulated smoke condensate generated from combustion of selected military burn pit contents on human airway epithelial cells.","authors":"Arunava Ghosh, Keith L Rogers, Samuel C Gallant, Yong Ho Kim, Julia E Rager, M Ian Gilmour, Scott H Randell, Ilona Jaspers","doi":"10.1186/s12989-024-00604-7","DOIUrl":"10.1186/s12989-024-00604-7","url":null,"abstract":"<p><strong>Background: </strong>Exposure to military burn pit smoke during deployment is associated with different respiratory and non-respiratory diseases. However, information linking smoke exposure to human pulmonary health is lacking. This study examined the effects of simulated burn pit smoke condensates on human airway epithelial cells (HAECs) from twelve donors (smokers/non-smokers, biological female/male) cultured at an air-liquid interface and exposed to condensates from three simulated burn pit waste materials (cardboard, plywood, and plastic) incinerated at two combustion conditions: smoldering and flaming. Cellular gene expression was analyzed using bulk RNA sequencing, and basolateral media cytokine levels were assessed using multiplex immunoassay.</p><p><strong>Results: </strong>Flaming smoke condensates caused more significant differentially expressed genes (DEGs) with plywood flaming smoke being the most potent in altering gene expression and modulating cytokine release. Cardboard and plywood flaming condensates primarily activated detoxification pathways, whereas plastic flaming affected genes related to anti-microbial and inflammatory responses. Correlation analysis between smoke condensate chemicals and gene expression to understand the underlying mechanism revealed crucial role of oxygenated polycyclic aromatic hydrocarbons (PAHs) and aluminum, molybdenum, and silicon elements; IL6 expression was positively correlated with most PAHs. Stratification of data based on HAEC donor demographics suggests that these affect gene expression changes. Enrichment analysis indicated similarity with several deployment-related presumptive and reported diseases, including asthma, emphysema, and cancer of different organs.</p><p><strong>Conclusions: </strong>This study highlights that simulated burn pit smoke exposure of HAECs causes gene expression changes indicative of deployment-related diseases with more pronounced effects seen in smokers and females. Future studies are needed to further characterize how sex and smoking status affect deployment-related diseases.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392370","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 pilot study of the cardiopulmonary effects in healthy volunteers after exposure to high levels of PM_2.5 in a New York City subway station.","authors":"David G Luglio, Kayla Rae Farrell, Terry Gordon","doi":"10.1186/s12989-024-00594-6","DOIUrl":"10.1186/s12989-024-00594-6","url":null,"abstract":"<p><strong>Background: </strong>Subway systems are becoming increasingly common worldwide transporting large populations in major cities. PM_2.5 concentrations have been demonstrated to be exceptionally high when underground, however. Studies on the impact of subway PM exposure on cardiopulmonary health in the United States are limited.</p><p><strong>Methods: </strong>Healthy volunteers in New York City were exposed to a 2-h visit on the 9th Street Station platform on the Port Authority Trans-Hudson train system. Blood pressure, heart rate variability (HRV), spirometry, and forced impulse oscillometry were measured, and urine, blood spot, and nasal swab biosamples were collected for cytokine analysis at the end of the 2-h exposure period. These endpoints were compared against individual control measurements collected after 2-h in a \"clean\" control space. In addition to paired comparisons, mixed effects models with subject as a random effect were employed to investigate the effect of the PM_2.5 concentrations and visit type (i.e., subway vs. control).</p><p><strong>Results: </strong>Mean PM_2.5 concentrations on the platform and during the control visit were 293.6 ± 65.7 (SD) and 4.6 ± 1.9 µg/m³, respectively. There was no change in any of the health metrics, but there was a non-significant trend for SDNN to be lower after subway exposure compared to control exposure. Total symptomatic scores did increase post-subway exposure compared to reported values prior to exposure or after the control visit. No significant changes in cytokine concentrations in any specimen type were observed. Mixed-effects models mostly corroborated these paired comparisons.</p><p><strong>Conclusions: </strong>Acute exposures to PM on a subway platform do not cause measurable cardiopulmonary effects apart from reductions in HRV and increases in symptoms in healthy volunteers. These findings match other studies that found little to no changes in lung function and blood pressure after exposure in underground subway stations. Future work should still target potentially more vulnerable populations, such as individuals with asthma or those who spend increased time underground on the subway such as transit workers.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392369","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":"Diesel exhaust particle inhalation in conjunction with high-fat diet consumption alters the expression of pulmonary SARS-COV-2 infection pathways, which is mitigated by probiotic treatment in C57BL/6 male mice.","authors":"Kayla Nguyen-Alley, Sarah Daniel, Danielle T Phillippi, Tyler D Armstrong, Bailee Johnson, Winston Ihemeremadu, Amie K Lund","doi":"10.1186/s12989-024-00601-w","DOIUrl":"https://doi.org/10.1186/s12989-024-00601-w","url":null,"abstract":"<p><strong>Background: </strong>Both exposure to air pollutants and obesity are associated with increased incidence and severity of COVID-19 infection; however, the mechanistic pathways involved are not well-characterized. After being primed by the transmembrane protease serine 2 (TMPRSS2) or furin protease, SARS-CoV-2 uses the angiotensin-converting enzyme (ACE)-2 receptor to enter respiratory epithelial cells. The androgen receptor (AR) is known to regulate both TMPRSS2 and ACE2 expression, and neuropilin-1 (NRP1) is a proposed coreceptor for SARS-CoV-2; thus, altered expression of these factors may promote susceptibility to infection. As such, this study investigated the hypothesis that inhalational exposure to traffic-generated particulate matter (diesel exhaust particulate; DEP) increases the expression of those pathways that mediate SARS-CoV-2 infection and susceptibility, which is exacerbated by the consumption of a high-fat (HF) diet.</p><p><strong>Methods: </strong>Four- to six-week-old male C57BL/6 mice fed either regular chow or a HF diet (HF, 45% kcal from fat) were randomly assigned to be exposed via oropharyngeal aspiration to 35 µg DEP suspended in 35 µl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. Furthermore, as previous studies have shown that probiotic treatment can protect against exposure-related inflammatory outcomes in the lungs, a subset of study animals fed a HF diet were concurrently treated with 0.3 g/day Winclove Ecologic^® Barrier probiotics in their drinking water throughout the study.</p><p><strong>Results: </strong>Our results revealed that the expression of ACE2 protein increased with DEP exposure and that TMPRSS2, AR, NRP1, and furin protein expression increased with DEP exposure in conjunction with a HF diet. These DEP ± HF diet-mediated increases in expression were mitigated with probiotic treatment.</p><p><strong>Conclusion: </strong>These findings suggest that inhalational exposure to air pollutants in conjunction with the consumption of a HF diet contributes to a more susceptible lung environment to SARS-CoV-2 infection and that probiotic treatment could be beneficial as a preventative measure.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351663","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":"Addressing the relevance of polystyrene nano- and microplastic particles used to support exposure, toxicity and risk assessment: implications and recommendations.","authors":"Todd Gouin, Robert Ellis-Hutchings, Mark Pemberton, Bianca Wilhelmus","doi":"10.1186/s12989-024-00599-1","DOIUrl":"https://doi.org/10.1186/s12989-024-00599-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;There has been an exponential increase in the number of studies reporting on the toxicological effects associated with exposure to nano and microplastic particles (NMPs). The majority of these studies, however, have used monodispersed polystyrene microspheres (PSMs) as 'model' particles. Here we review the differences between the manufacture and resulting physicochemical properties of polystyrene used in commerce and the PSMs most commonly used in toxicity studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main body: &lt;/strong&gt;In general, we demonstrate that significant complexity exists as to the properties of polystyrene particles. Differences in chemical composition, size, shape, surface functionalities and other aspects raise doubt as to whether PSMs are fit-for-purpose for the study of potential adverse effects of naturally occurring NMPs. A realistic assessment of potential health implications of the exposure to environmental NMPs requires better characterisation of the particles, a robust mechanistic understanding of their interactions and effects in biological systems as well as standardised protocols to generate relevant model particles. It is proposed that multidisciplinary engagement is necessary for the development of a timely and effective strategy towards this end. We suggest a holistic framework, which must be supported by a multidisciplinary group of experts to work towards either providing access to a suite of environmentally relevant NMPs and/or developing guidance with respect to best practices that can be adopted by research groups to generate and reliably use NMPs. It is emphasized that there is a need for this group to agree to a consensus regarding what might best represent a model NMP that is consistent with environmental exposure for human health, and which can be used to support a variety of ongoing research needs, including those associated with exposure and hazard assessment, mechanistic toxicity studies, toxicokinetics and guidance regarding the prioritization of plastic and NMPs that likely represent the greatest risk to human health. It is important to acknowledge, however, that establishing a multidisciplinary group, or an expert community of practice, represents a non-trivial recommendation, and will require significant resources in terms of expertise and funding.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;There is currently an opportunity to bring together a multidisciplinary group of experts, including polymer chemists, material scientists, mechanical engineers, exposure and life-cycle assessment scientists, toxicologists, microbiologists and analytical chemists, to provide leadership and guidance regarding a consensus on defining what best represents environmentally relevant NMPs. We suggest that given the various complex issues surrounding the environmental and human health implications that exposure to NMPs represents, that a multidisciplinary group of experts are thus critical towards helping to progress the harm","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351662","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":"The chemical composition of secondary organic aerosols regulates transcriptomic and metabolomic signaling in an epithelial-endothelial in vitro coculture","authors":"Svenja Offer, Sebastiano Di Bucchianico, Hendryk Czech, Michal Pardo, Jana Pantzke, Christoph Bisig, Eric Schneider, Stefanie Bauer, Elias J. Zimmermann, Sebastian Oeder, Elena Hartner, Thomas Gröger, Rasha Alsaleh, Christian Kersch, Till Ziehm, Thorsten Hohaus, Christopher P. Rüger, Simone Schmitz-Spanke, Jürgen Schnelle-Kreis, Martin Sklorz, Astrid Kiendler-Scharr, Yinon Rudich, Ralf Zimmermann","doi":"10.1186/s12989-024-00600-x","DOIUrl":"https://doi.org/10.1186/s12989-024-00600-x","url":null,"abstract":"The formation of secondary organic aerosols (SOA) by atmospheric oxidation reactions substantially contributes to the burden of fine particulate matter (PM2.5), which has been associated with adverse health effects (e.g., cardiovascular diseases). However, the molecular and cellular effects of atmospheric aging on aerosol toxicity have not been fully elucidated, especially in model systems that enable cell-to-cell signaling. In this study, we aimed to elucidate the complexity of atmospheric aerosol toxicology by exposing a coculture model system consisting of an alveolar (A549) and an endothelial (EA.hy926) cell line seeded in a 3D orientation at the air‒liquid interface for 4 h to model aerosols. Simulation of atmospheric aging was performed on volatile biogenic (β-pinene) or anthropogenic (naphthalene) precursors of SOA condensing on soot particles. The similar physical properties for both SOA, but distinct differences in chemical composition (e.g., aromatic compounds, oxidation state, unsaturated carbonyls) enabled to determine specifically induced toxic effects of SOA. In A549 cells, exposure to naphthalene-derived SOA induced stress-related airway remodeling and an early type I immune response to a greater extent. Transcriptomic analysis of EA.hy926 cells not directly exposed to aerosol and integration with metabolome data indicated generalized systemic effects resulting from the activation of early response genes and the involvement of cardiovascular disease (CVD) -related pathways, such as the intracellular signal transduction pathway (PI3K/AKT) and pathways associated with endothelial dysfunction (iNOS; PDGF). Greater induction following anthropogenic SOA exposure might be causative for the observed secondary genotoxicity. Our findings revealed that the specific effects of SOA on directly exposed epithelial cells are highly dependent on the chemical identity, whereas non directly exposed endothelial cells exhibit more generalized systemic effects with the activation of early stress response genes and the involvement of CVD-related pathways. However, a greater correlation was made between the exposure to the anthropogenic SOA compared to the biogenic SOA. In summary, our study highlights the importance of chemical aerosol composition and the use of cell systems with cell-to-cell interplay on toxicological outcomes. ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide DNA methylation sequencing reveals the involvement of ferroptosis in hepatotoxicity induced by dietary exposure to food-grade titanium dioxide","authors":"Jiaxin Shang, Jun Yan, He Lou, Rongshang Shou, Yingqi Zhan, Xiaoyan Lu, Xiaohui Fan","doi":"10.1186/s12989-024-00598-2","DOIUrl":"https://doi.org/10.1186/s12989-024-00598-2","url":null,"abstract":"Following the announcement by the European Food Safety Authority that the food additive titanium dioxide (E 171) is unsafe for human consumption, and the subsequent ban by the European Commission, concerns have intensified over the potential risks E 171 poses to human vital organs. The liver is the main organ for food-grade nanoparticle metabolism. It is increasingly being found that epigenetic changes may play an important role in nanomaterial-induced hepatotoxicity. However, the profound effects of E 171 on the liver, especially at the epigenetic level, remain largely unknown. Mice were exposed orally to human-relevant doses of two types of E 171 mixed in diet for 28 and/or 84 days. Conventional toxicology and global DNA methylation analyses were performed to assess E 171-induced hepatotoxicity and epigenetic changes. Whole genome bisulfite sequencing and further ferroptosis protein detection were used to reveal E 171-induced changes in liver methylation profiles and toxic mechanisms. Exposed to E 171 for 28 and/or 84 days resulted in reduced global DNA methylation and hydroxymethylation in the liver of mice. E 171 exposure for 84 days elicited inflammation and damage in the mouse liver, whereas 28-day exposure did not. Whole-genome DNA methylation sequencing disclosed substantial methylation alterations at the CG and non-CG sites of the liver DNA in mice exposed to E 171 for 84 days. Mechanistic analysis of the DNA methylation alterations indicated that ferroptosis contributed to the liver toxicity induced by E 171. E 171-induced DNA methylation changes triggered NCOA4-mediated ferritinophagy, attenuated the protein levels of GPX4, FTH1, and FTL in the liver, and thereby caused ferroptosis. Long-term oral exposure to E 171 triggers hepatotoxicity and induces methylation changes in both CG and non-CG sites of liver DNA. These epigenetic alterations activate ferroptosis in the liver through NCOA4-mediated ferritinophagy, highlighting the role of DNA methylation and ferroptosis in the potential toxicity caused by E 171 in vivo.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microplastics caused embryonic growth retardation and placental dysfunction in pregnant mice by activating GRP78/IRE1α/JNK axis induced apoptosis and endoplasmic reticulum stress","authors":"Jun Bai, Yuzeng Wang, Siwei Deng, Ying Yang, Sheng Chen, Zhenlong Wu","doi":"10.1186/s12989-024-00595-5","DOIUrl":"https://doi.org/10.1186/s12989-024-00595-5","url":null,"abstract":"Microplastics (MPs), a brand-new class of worldwide environmental pollutant, have received a lot of attention. MPs are consumed by both humans and animals through water, food chain and other ways, which may cause potential health risks. However, the effects of MPs on embryonic development, especially placental function, and its related mechanisms still need to be further studied. We investigated the impact on fetal development and placental physiological function of pregnant mice by consecutive gavages of MPs at 0, 25, 50, 100 mg/kg body weight during gestational days (GDs 0–14). The results showed that continuous exposure to high concentrations of MP significantly reduced daily weight gain and impaired reproductive performance of pregnant mice. In addition, MPs could significantly induce oxidative stress and placental dysfunction in pregnant mice. On the other hand, MPs exposure significantly decreased placental barrier function and induced placental inflammation. Specifically, MPs treatment significantly reduced the expression of tight junction proteins in placentas, accompanied by inflammatory cell infiltration and increased mRNA levels of pro-inflammatory cytokines and chemokines in placentas. Finally, we found that MPs induced placental apoptosis and endoplasmic reticulum (ER) stress through the GRP78/IRE1α/JNK axis, leading to placental dysfunction and decreased reproductive performance in pregnant mice. We revealed for the first time that the effects of MPs on placental dysfunction in pregnant animals. Blocking the targets of MPs mediated ER stress will provide potential therapeutic ideas for the toxic effects of MPs on maternal pregnancy.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}