Particle and Fibre Toxicology最新文献

{"title":"Zinc oxide nanoparticles exacerbate skin epithelial cell damage by upregulating pro-inflammatory cytokines and exosome secretion in M1 macrophages following UVB irradiation-induced skin injury.","authors":"Bour-Jr Wang, Yu-Ying Chen, Hui-Hsuan Chang, Rong-Jane Chen, Ying-Jan Wang, Yu-Hsuan Lee","doi":"10.1186/s12989-024-00571-z","DOIUrl":"10.1186/s12989-024-00571-z","url":null,"abstract":"<p><strong>Background: </strong>Zinc oxide nanoparticles (ZnONPs) are common materials used in skin-related cosmetics and sunscreen products due to their whitening and strong UV light absorption properties. Although the protective effects of ZnONPs against UV light in intact skin have been well demonstrated, the effects of using ZnONPs on damaged or sunburned skin are still unclear. In this study, we aimed to reveal the detailed underlying mechanisms related to keratinocytes and macrophages exposed to UVB and ZnONPs.</p><p><strong>Results: </strong>We demonstrated that ZnONPs exacerbated mouse skin damage after UVB exposure, followed by increased transepidermal water loss (TEWL) levels, cell death and epithelial thickness. In addition, ZnONPs could penetrate through the damaged epithelium, gain access to the dermis cells, and lead to severe inflammation by activation of M1 macrophage. Mechanistic studies indicated that co-exposure of keratinocytes to UVB and ZnONPs lysosomal impairment and autophagy dysfunction, which increased cell exosome release. However, these exosomes could be taken up by macrophages, which accelerated M1 macrophage polarization. Furthermore, ZnONPs also induced a lasting inflammatory response in M1 macrophages and affected epithelial cell repair by regulating the autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion.</p><p><strong>Conclusions: </strong>Our findings propose a new concept for ZnONP-induced skin toxicity mechanisms and the safety issue of ZnONPs application on vulnerable skin. The process involved an interplay of lysosomal impairment, autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. The current finding is valuable for evaluating the effects of ZnONPs for cosmetics applications.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"9"},"PeriodicalIF":7.2,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990806","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":"Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles.","authors":"Lisa Mf Janssen, Frauke Lemaire, Nora Fopke Marain, Steven Ronsmans, Natasja Heylen, Arno Vanstapel, Greetje Vande Velde, Jeroen Aj Vanoirbeek, Kenneth Michael Pollard, Manosij Ghosh, Peter Hm Hoet","doi":"10.1186/s12989-024-00569-7","DOIUrl":"10.1186/s12989-024-00569-7","url":null,"abstract":"<p><strong>Background: </strong>Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization.</p><p><strong>Results: </strong>The findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains.</p><p><strong>Conclusion: </strong>Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"8"},"PeriodicalIF":7.2,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972967","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":"Effective density of inhaled environmental and engineered nanoparticles and its impact on the lung deposition and dosimetry","authors":"Denisa Lizonova, Amogh Nagarkar, Philip Demokritou, Georgios A. Kelesidis","doi":"10.1186/s12989-024-00567-9","DOIUrl":"https://doi.org/10.1186/s12989-024-00567-9","url":null,"abstract":"Airborne environmental and engineered nanoparticles (NPs) are inhaled and deposited in the respiratory system. The inhaled dose of such NPs and their deposition location in the lung determines their impact on health. When calculating NP deposition using particle inhalation models, a common approach is to use the bulk material density, ρb, rather than the effective density, ρeff. This neglects though the porous agglomerate structure of NPs and may result in a significant error of their lung-deposited dose and location. Here, the deposition of various environmental NPs (aircraft and diesel black carbon, wood smoke) and engineered NPs (silica, zirconia) in the respiratory system of humans and mice is calculated using the Multiple-Path Particle Dosimetry model accounting for their realistic structure and effective density. This is done by measuring the NP ρeff which was found to be up to one order of magnitude smaller than ρb. Accounting for the realistic ρeff of NPs reduces their deposited mass in the pulmonary region of the respiratory system up to a factor of two in both human and mouse models. Neglecting the ρeff of NPs does not alter significantly the distribution of the deposited mass fractions in the human or mouse respiratory tract that are obtained by normalizing the mass deposited at the head, tracheobronchial and pulmonary regions by the total deposited mass. Finally, the total deposited mass fraction derived this way is in excellent agreement with those measured in human studies for diesel black carbon. The doses of inhaled NPs are overestimated by inhalation particle deposition models when the ρb is used instead of the real-world effective density which can vary significantly due to the porous agglomerate structure of NPs. So the use of realistic ρeff, which can be measured as described here, is essential to determine the lung deposition and dosimetry of inhaled NPs and their impact on public health. ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"50 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139771007","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":"Particulate matter from car exhaust alters function of human iPSC-derived microglia.","authors":"Henna Jäntti, Steffi Jonk, Mireia Gómez Budia, Sohvi Ohtonen, Ilkka Fagerlund, Mohammad Feroze Fazaludeen, Päivi Aakko-Saksa, Alice Pebay, Šárka Lehtonen, Jari Koistinaho, Katja M Kanninen, Pasi I Jalava, Tarja Malm, Paula Korhonen","doi":"10.1186/s12989-024-00564-y","DOIUrl":"10.1186/s12989-024-00564-y","url":null,"abstract":"<p><strong>Background: </strong>Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer's disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia.</p><p><strong>Results: </strong>Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml^-1 increased microglial survival whereas higher concentrations became toxic over time. Both tested pollutants impaired microglial phagocytosis and increased secretion of a few proinflammatory cytokines with distinct patterns, compared to lipopolysaccharide induced responses. iMGLs showed pollutant dependent responses to production of reactive oxygen species (ROS) with CNG inducing and EN590 reducing ROS production.</p><p><strong>Conclusions: </strong>Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"6"},"PeriodicalIF":7.2,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10870637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741690","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":"Influence of polyethylene terephthalate (PET) microplastic on selected active substances in the intramural neurons of the porcine duodenum.","authors":"Ismena Gałęcka, Natalia Szyryńska, Jarosław Całka","doi":"10.1186/s12989-024-00566-w","DOIUrl":"10.1186/s12989-024-00566-w","url":null,"abstract":"<p><strong>Background: </strong>Currently, society and industry generate huge amounts of plastics worldwide. The ubiquity of microplastics is obvious, but its impact on the animal and human organism remains not fully understood. The digestive tract is one of the first barriers between pathogens and xenobiotics and a living organism. Its proper functioning is extremely important in order to maintain homeostasis. The aim of this study was to determine the effect of microplastic on enteric nervous system and histological structure of swine duodenum. The experiment was carried out on 15 sexually immature gilts, approximately 8 weeks old. The animals were randomly divided into 3 study groups (n = 5/group). The control group received empty gelatin capsules once a day for 28 days, the first research group received daily gelatin capsules with polyethylene terephthalate (PET) particles as a mixture of particles of various sizes (maximum particle size 300 µm) at a dose of 0.1 g/animal/day. The second study group received a dose ten times higher-1 g/animal/day.</p><p><strong>Results: </strong>A dose of 1 g/day/animal causes more changes in the enteric nervous system and in the histological structure of duodenum. Statistically significant differences in the expression of cocaine and amphetamine regulated transcript, galanin, neuronal nitric oxide synthase, substance P, vesicular acetylcholine transporter and vasoactive intestinal peptide between control and high dose group was noted. The histopathological changes were more frequently observed in the pigs receiving higher dose of PET.</p><p><strong>Conclusion: </strong>Based on this study it may be assumed, that oral intake of microplastic might have potential negative influence on digestive tract, but it is dose-dependent.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"5"},"PeriodicalIF":7.2,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698075","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 in vitro gastrointestinal digestion-associated protein corona of polystyrene nano- and microplastics increases their uptake by human THP-1-derived macrophages","authors":"Hugo Brouwer, Mojtaba Porbahaie, Sjef Boeren, Mathias Busch, Hans Bouwmeester","doi":"10.1186/s12989-024-00563-z","DOIUrl":"https://doi.org/10.1186/s12989-024-00563-z","url":null,"abstract":"Micro- and nanoplastics (MNPs) represent one of the most widespread environmental pollutants of the twenty-first century to which all humans are orally exposed. Upon ingestion, MNPs pass harsh biochemical conditions within the gastrointestinal tract, causing a unique protein corona on the MNP surface. Little is known about the digestion-associated protein corona and its impact on the cellular uptake of MNPs. Here, we systematically studied the influence of gastrointestinal digestion on the cellular uptake of neutral and charged polystyrene MNPs using THP-1-derived macrophages. The protein corona composition was quantified using LC‒MS–MS-based proteomics, and the cellular uptake of MNPs was determined using flow cytometry and confocal microscopy. Gastrointestinal digestion resulted in a distinct protein corona on MNPs that was retained in serum-containing cell culture medium. Digestion increased the uptake of uncharged MNPs below 500 nm by 4.0–6.1-fold but did not affect the uptake of larger sized or charged MNPs. Forty proteins showed a good correlation between protein abundance and MNP uptake, including coagulation factors, apolipoproteins and vitronectin. This study provides quantitative data on the presence of gastrointestinal proteins on MNPs and relates this to cellular uptake, underpinning the need to include the protein corona in hazard assessment of MNPs. ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"39 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139677629","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":"Comparison of PET tracing and biodistribution between 64Cu-labeled micro-and nano-polystyrene in a murine inhalation model","authors":"Joycie Shanmugiah, Javeria Zaheer, Changkeun Im, Choong Mo Kang, Jin Su Kim","doi":"10.1186/s12989-023-00561-7","DOIUrl":"https://doi.org/10.1186/s12989-023-00561-7","url":null,"abstract":"Recent studies showed the presence of microplastic in human lungs. There remains an unmet need to identify the biodistribution of microplastic after inhalation. In this study, we traced the biodistribution of inhaled micro-sized polystyrene (mPS) and/or nano-sized PS (nPS) using 64Cu with PET in mice. We used 0.2–0.3-µm sized mPS and 20-nm sized nPS throughout. 64Cu-DOTA-mPS, 64Cu-DOTA-nPS and/or 64CuCl2 were used to trace the distribution in the murine inhalation model. PET images were acquired using an INVEON PET scanner at 1, 12, 24, 48, and 72 h after intratracheal instillation, and the SUVmax for interesting organs were determined, biodistribution was then determined in terms of percentage injected dose/gram of tissue (%ID/g). Ex vivo tissue-radio thin-layer chromatography (Ex vivo-radioTLC) was used to demonstrate the existence of 64Cu-DOTA-PS in tissue. PET image demonstrated that the amount of 64Cu-DOTA-mPS retained within the lung was significantly higher than 64Cu-DOTA-nPS until 72 h; SUVmax values of 64Cu-DOTA-mPS in lungs was 11.7 ± 5.0, 48.3 ± 6.2, 65.5 ± 2.3, 42.2 ± 13.1, and 13.2 ± 2.3 at 1, 12, 24, 48, and 72 h respectively whereas it was 31.2 ± 3.1, 17.3 ± 5.9, 10.0 ± 3.4, 8.1 ± 2.4 and 8.9 ± 3.6 for 64Cu-DOTA-nPS at the corresponding timepoints. The biodistribution data supported the PET data with a similar pattern of clearance of the radioactivity from the lung. nPS cleared rapidly post instillation in comparison to mPS within the lungs. Higher accumulation of %ID/g for nPS (roughly 2 times) were observed compared to mPS in spleen, liver, intestine, thymus, kidney, brain, salivary gland, ovary, and urinary bladder. Ex vivo-radioTLC was used to demonstrate that the detected gamma rays originated from 64Cu-DOTA-mPS or nPS. PET image demonstrated the differences in accumulations of mPS and/or nPS between lungs and other interesting organs. The information provided may be used as the basis for future studies on the toxicity of mPS and/or nPS. ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"66 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646636","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":"Malignant peritoneal mesotheliomas of rats induced by multiwalled carbon nanotubes and amosite asbestos: transcriptome and epigenetic profiles","authors":"Stella Marie Reamon-Buettner, Susanne Rittinghausen, Annika Klauke, Andreas Hiemisch, Christina Ziemann","doi":"10.1186/s12989-024-00565-x","DOIUrl":"https://doi.org/10.1186/s12989-024-00565-x","url":null,"abstract":"Malignant mesothelioma is an aggressive cancer that often originates in the pleural and peritoneal mesothelium. Exposure to asbestos is a frequent cause. However, studies in rodents have shown that certain multiwalled carbon nanotubes (MWCNTs) can also induce malignant mesothelioma. The exact mechanisms are still unclear. To gain further insights into molecular pathways leading to carcinogenesis, we analyzed tumors in Wistar rats induced by intraperitoneal application of MWCNTs and amosite asbestos. Using transcriptomic and epigenetic approaches, we compared the tumors by inducer (MWCNTs or amosite asbestos) or by tumor type (sarcomatoid, epithelioid, or biphasic). Genome-wide transcriptome datasets, whether grouped by inducer or tumor type, showed a high number of significant differentially expressed genes (DEGs) relative to control peritoneal tissues. Bioinformatic evaluations using Ingenuity Pathway Analysis (IPA) revealed that while the transcriptome datasets shared commonalities, they also showed differences in DEGs, regulated canonical pathways, and affected molecular functions. In all datasets, among highly- scoring predicted canonical pathways were Phagosome Formation, IL8 Signaling, Integrin Signaling, RAC Signaling, and TREM1 Signaling. Top-scoring activated molecular functions included cell movement, invasion of cells, migration of cells, cell transformation, and metastasis. Notably, we found many genes associated with malignant mesothelioma in humans, which showed similar expression changes in the rat tumor transcriptome datasets. Furthermore, RT-qPCR revealed downregulation of Hrasls, Nr4a1, Fgfr4, and Ret or upregulation of Rnd3 and Gadd45b in all or most of the 36 tumors analyzed. Bisulfite sequencing of Hrasls, Nr4a1, Fgfr4, and Ret revealed heterogeneity in DNA methylation of promoter regions. However, higher methylation percentages were observed in some tumors compared to control tissues. Lastly, global 5mC DNA, m6A RNA and 5mC RNA methylation levels were also higher in tumors than in control tissues. Our findings may help better understand how exposure to MWCNTs can lead to carcinogenesis. This information is valuable for risk assessment and in the development of safe-by-design strategies.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"196 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646634","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":"ROS/mtROS promotes TNTs formation via the PI3K/AKT/mTOR pathway to protect against mitochondrial damages in glial cells induced by engineered nanomaterials","authors":"Xinpei Lin, Wei Wang, Xiangyu Chang, Cheng Chen, Zhenkun Guo, Guangxia Yu, Wenya Shao, Siying Wu, Qunwei Zhang, Fuli Zheng, Huangyuan Li","doi":"10.1186/s12989-024-00562-0","DOIUrl":"https://doi.org/10.1186/s12989-024-00562-0","url":null,"abstract":"As the demand and application of engineered nanomaterials have increased, their potential toxicity to the central nervous system has drawn increasing attention. Tunneling nanotubes (TNTs) are novel cell–cell communication that plays a crucial role in pathology and physiology. However, the relationship between TNTs and nanomaterials neurotoxicity remains unclear. Here, three types of commonly used engineered nanomaterials, namely cobalt nanoparticles (CoNPs), titanium dioxide nanoparticles (TiO2NPs), and multi-walled carbon nanotubes (MWCNTs), were selected to address this limitation. After the complete characterization of the nanomaterials, the induction of TNTs formation with all of the nanomaterials was observed using high-content screening system and confocal microscopy in both primary astrocytes and U251 cells. It was further revealed that TNT formation protected against nanomaterial-induced neurotoxicity due to cell apoptosis and disrupted ATP production. We then determined the mechanism underlying the protective role of TNTs. Since oxidative stress is a common mechanism in nanotoxicity, we first observed a significant increase in total and mitochondrial reactive oxygen species (namely ROS, mtROS), causing mitochondrial damage. Moreover, pretreatment of U251 cells with either the ROS scavenger N-acetylcysteine or the mtROS scavenger mitoquinone attenuated nanomaterial-induced neurotoxicity and TNTs generation, suggesting a central role of ROS in nanomaterials-induced TNTs formation. Furthermore, a vigorous downstream pathway of ROS, the PI3K/AKT/mTOR pathway, was found to be actively involved in nanomaterials-promoted TNTs development, which was abolished by LY294002, Perifosine and Rapamycin, inhibitors of PI3K, AKT, and mTOR, respectively. Finally, western blot analysis demonstrated that ROS and mtROS scavengers suppressed the PI3K/AKT/mTOR pathway, which abrogated TNTs formation. Despite their biophysical properties, various types of nanomaterials promote TNTs formation and mitochondrial transfer, preventing cell apoptosis and disrupting ATP production induced by nanomaterials. ROS/mtROS and the activation of the downstream PI3K/AKT/mTOR pathway are common mechanisms to regulate TNTs formation and mitochondrial transfer. Our study reveals that engineered nanomaterials share the same molecular mechanism of TNTs formation and intercellular mitochondrial transfer, and the proposed adverse outcome pathway contributes to a better understanding of the intercellular protection mechanism against nanomaterials-induced neurotoxicity. ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"5 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471168","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":"Acute and continuous exposure of airborne fine particulate matter (PM2.5): diverse outer blood–retinal barrier damages and disease susceptibilities","authors":"Yuzhou Gu, Feiyin Sheng, Mengqin Gao, Li Zhang, Shengjie Hao, Shuying Chen, Rongrong Chen, Yili Xu, Di Wu, Yu Han, Lu Chen, Ye Liu, Bing Lu, Wei Zhao, Xiaoming Lou, Zhijian Chen, Peng Li, Xiaofeng Wang, Ke Yao, Qiuli Fu","doi":"10.1186/s12989-023-00558-2","DOIUrl":"https://doi.org/10.1186/s12989-023-00558-2","url":null,"abstract":"The association between air pollution and retinal diseases such as age-related macular degeneration (AMD) has been demonstrated, but the pathogenic correlation is unknown. Damage to the outer blood–retinal barrier (oBRB), which consists of the retinal pigment epithelium (RPE) and choriocapillaris, is crucial in the development of fundus diseases. To describe the effects of airborne fine particulate matter (PM2.5) on the oBRB and disease susceptibilities. A PM2.5-exposed mice model was established through the administration of eye drops containing PM2.5. Optical coherence tomography angiography, transmission electron microscope, RPE immunofluorescence staining and Western blotting were applied to study the oBRB changes. A co-culture model of ARPE-19 cells with stretching vascular endothelial cells was established to identify the role of choroidal vasodilatation in PM2.5-associated RPE damage. Acute exposure to PM2.5 resulted in choroidal vasodilatation, RPE tight junctions impairment, and ultimately an increased risk of retinal edema in mice. These manifestations are very similar to the pachychoroid disease represented by central serous chorioretinopathy (CSC). After continuous PM2.5 exposure, the damage to the RPE was gradually repaired, but AMD-related early retinal degenerative changes appeared under continuous choroidal inflammation. This study reveals oBRB pathological changes under different exposure durations, providing a valuable reference for the prevention of PM2.5-related fundus diseases and public health policy formulation. ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"31 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716339","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}