Pub Date : 2024-04-10DOI: 10.1186/s12989-024-00580-y
Min Chen, Siyuan Chen, Xinyu Wang, Zongjian Ye, Kehan Liu, Yijing Qian, Meng Tang, Tianshu Wu
Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development. In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson’s disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures. These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.
{"title":"The discovery of regional neurotoxicity-associated metabolic alterations induced by carbon quantum dots in brain of mice using a spatial metabolomics analysis","authors":"Min Chen, Siyuan Chen, Xinyu Wang, Zongjian Ye, Kehan Liu, Yijing Qian, Meng Tang, Tianshu Wu","doi":"10.1186/s12989-024-00580-y","DOIUrl":"https://doi.org/10.1186/s12989-024-00580-y","url":null,"abstract":"Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development. In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson’s disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures. These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"188 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563273","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}
Pub Date : 2024-04-02DOI: 10.1186/s12989-024-00581-x
Stephanie Wright, Flemming R. Cassee, Aaron Erdely, Matthew J. Campen
Micro- and nanoplastic particles (MNP) are omnipresent as either pollution or intentionally used in consumer products, released from packaging or even food. There is an exponential increase in the production of plastics. With the realization of bioaccumulation in humans, toxicity research is quickly expanding. There is a rapid increase in the number of papers published on the potential implications of exposure to MNP which necessitates a call for quality criteria to be applied when doing the research. At present, most papers on MNP describe the effects of commercially available polymer (mostly polystyrene) beads that are typically not the MNP of greatest concern. This is not a fault of the research community, necessarily, as the MNPs to which humans are exposed are usually not available in the quantities needed for toxicological research and innovations are needed to supply environmentally-relevant MNP models. In addition, like we have learned from decades of research with particulate matter and engineered nanomaterials, sample physicochemical characteristics and preparation can have major impacts on the biological responses and interpretation of the research findings. Lastly, MNP dosimetry may pose challenges as (1) we are seeing early evidence that plastics are already in the human body at quite high levels that may be difficult to achieve in acute in vitro studies and (2) plastics are already in the diets fed to preclinical models. This commentary highlights the pitfalls and recommendations for particle and fibre toxicologists that should be considered when performing and disseminating the research.
{"title":"Micro- and nanoplastics concepts for particle and fibre toxicologists","authors":"Stephanie Wright, Flemming R. Cassee, Aaron Erdely, Matthew J. Campen","doi":"10.1186/s12989-024-00581-x","DOIUrl":"https://doi.org/10.1186/s12989-024-00581-x","url":null,"abstract":"Micro- and nanoplastic particles (MNP) are omnipresent as either pollution or intentionally used in consumer products, released from packaging or even food. There is an exponential increase in the production of plastics. With the realization of bioaccumulation in humans, toxicity research is quickly expanding. There is a rapid increase in the number of papers published on the potential implications of exposure to MNP which necessitates a call for quality criteria to be applied when doing the research. At present, most papers on MNP describe the effects of commercially available polymer (mostly polystyrene) beads that are typically not the MNP of greatest concern. This is not a fault of the research community, necessarily, as the MNPs to which humans are exposed are usually not available in the quantities needed for toxicological research and innovations are needed to supply environmentally-relevant MNP models. In addition, like we have learned from decades of research with particulate matter and engineered nanomaterials, sample physicochemical characteristics and preparation can have major impacts on the biological responses and interpretation of the research findings. Lastly, MNP dosimetry may pose challenges as (1) we are seeing early evidence that plastics are already in the human body at quite high levels that may be difficult to achieve in acute in vitro studies and (2) plastics are already in the diets fed to preclinical models. This commentary highlights the pitfalls and recommendations for particle and fibre toxicologists that should be considered when performing and disseminating the research.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"49 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563275","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}
Pub Date : 2024-04-01DOI: 10.1186/s12989-024-00579-5
Xueyan Li, Hailin Xu, Xinying Zhao, Yan Li, Songqing Lv, Wei Zhou, Ji Wang, Zhiwei Sun, Yanbo Li, Caixia Guo
Background: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described.
Results: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation.
Conclusions: Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products.
{"title":"Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling.","authors":"Xueyan Li, Hailin Xu, Xinying Zhao, Yan Li, Songqing Lv, Wei Zhou, Ji Wang, Zhiwei Sun, Yanbo Li, Caixia Guo","doi":"10.1186/s12989-024-00579-5","DOIUrl":"10.1186/s12989-024-00579-5","url":null,"abstract":"<p><strong>Background: </strong>Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described.</p><p><strong>Results: </strong>We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation.</p><p><strong>Conclusions: </strong>Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"17"},"PeriodicalIF":7.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336489","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}
Pub Date : 2024-03-21DOI: 10.1186/s12989-024-00577-7
Todd A Stueckle, Jake Jensen, Jayme P Coyle, Raymond Derk, Alixandra Wagner, Cerasela Zoica Dinu, Tiffany G Kornberg, Sherri A Friend, Alan Dozier, Sushant Agarwal, Rakesh K Gupta, Liying W Rojanasakul
<p><strong>Background: </strong>Organomodified nanoclays (ONC), two-dimensional montmorillonite with organic coatings, are increasingly used to improve nanocomposite properties. However, little is known about pulmonary health risks along the nanoclay life cycle even with increased evidence of airborne particulate exposures in occupational environments. Recently, oropharyngeal aspiration exposure to pre- and post-incinerated ONC in mice caused low grade, persistent lung inflammation with a pro-fibrotic signaling response with unknown mode(s) of action. We hypothesized that the organic coating presence and incineration status of nanoclays determine the inflammatory cytokine secretary profile and cytotoxic response of macrophages. To test this hypothesis differentiated human macrophages (THP-1) were acutely exposed (0-20 µg/cm<sup>2</sup>) to pristine, uncoated nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS) followed by cytotoxicity and inflammatory endpoints. Macrophages were co-exposed to lipopolysaccharide (LPS) or LPS-free medium to assess the role of priming the NF-κB pathway in macrophage response to nanoclay treatment. Data were compared to inflammatory responses in male C57Bl/6J mice following 30 and 300 µg/mouse aspiration exposure to the same particles.</p><p><strong>Results: </strong>In LPS-free media, CloisNa exposure caused mitochondrial depolarization while Clois30B exposure caused reduced macrophage viability, greater cytotoxicity, and significant damage-associated molecular patterns (IL-1α and ATP) release compared to CloisNa and unexposed controls. LPS priming with low CloisNa doses caused elevated cathepsin B/Caspage-1/IL-1β release while higher doses resulted in apoptosis. Clois30B exposure caused dose-dependent THP-1 cell pyroptosis evidenced by Cathepsin B and IL-1β release and Gasdermin D cleavage. Incineration ablated the cytotoxic and inflammatory effects of Clois30B while I-CloisNa still retained some mild inflammatory potential. Comparative analyses suggested that in vitro macrophage cell viability, inflammasome endpoints, and pro-inflammatory cytokine profiles significantly correlated to mouse bronchioalveolar lavage inflammation metrics including inflammatory cell recruitment.</p><p><strong>Conclusions: </strong>Presence of organic coating and incineration status influenced inflammatory and cytotoxic responses following exposure to human macrophages. Clois30B, with a quaternary ammonium tallow coating, induced a robust cell membrane damage and pyroptosis effect which was eliminated after incineration. Conversely, incinerated nanoclay exposure primarily caused elevated inflammatory cytokine release from THP-1 cells. Collectively, pre-incinerated nanoclay displayed interaction with macrophage membrane components (molecular initiating event), increased pro-inflammatory mediators, and increased inflammatory cell recruitment (two key events) in the lun
{"title":"In vitro inflammation and toxicity assessment of pre- and post-incinerated organomodified nanoclays to macrophages using high-throughput screening approaches.","authors":"Todd A Stueckle, Jake Jensen, Jayme P Coyle, Raymond Derk, Alixandra Wagner, Cerasela Zoica Dinu, Tiffany G Kornberg, Sherri A Friend, Alan Dozier, Sushant Agarwal, Rakesh K Gupta, Liying W Rojanasakul","doi":"10.1186/s12989-024-00577-7","DOIUrl":"10.1186/s12989-024-00577-7","url":null,"abstract":"<p><strong>Background: </strong>Organomodified nanoclays (ONC), two-dimensional montmorillonite with organic coatings, are increasingly used to improve nanocomposite properties. However, little is known about pulmonary health risks along the nanoclay life cycle even with increased evidence of airborne particulate exposures in occupational environments. Recently, oropharyngeal aspiration exposure to pre- and post-incinerated ONC in mice caused low grade, persistent lung inflammation with a pro-fibrotic signaling response with unknown mode(s) of action. We hypothesized that the organic coating presence and incineration status of nanoclays determine the inflammatory cytokine secretary profile and cytotoxic response of macrophages. To test this hypothesis differentiated human macrophages (THP-1) were acutely exposed (0-20 µg/cm<sup>2</sup>) to pristine, uncoated nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS) followed by cytotoxicity and inflammatory endpoints. Macrophages were co-exposed to lipopolysaccharide (LPS) or LPS-free medium to assess the role of priming the NF-κB pathway in macrophage response to nanoclay treatment. Data were compared to inflammatory responses in male C57Bl/6J mice following 30 and 300 µg/mouse aspiration exposure to the same particles.</p><p><strong>Results: </strong>In LPS-free media, CloisNa exposure caused mitochondrial depolarization while Clois30B exposure caused reduced macrophage viability, greater cytotoxicity, and significant damage-associated molecular patterns (IL-1α and ATP) release compared to CloisNa and unexposed controls. LPS priming with low CloisNa doses caused elevated cathepsin B/Caspage-1/IL-1β release while higher doses resulted in apoptosis. Clois30B exposure caused dose-dependent THP-1 cell pyroptosis evidenced by Cathepsin B and IL-1β release and Gasdermin D cleavage. Incineration ablated the cytotoxic and inflammatory effects of Clois30B while I-CloisNa still retained some mild inflammatory potential. Comparative analyses suggested that in vitro macrophage cell viability, inflammasome endpoints, and pro-inflammatory cytokine profiles significantly correlated to mouse bronchioalveolar lavage inflammation metrics including inflammatory cell recruitment.</p><p><strong>Conclusions: </strong>Presence of organic coating and incineration status influenced inflammatory and cytotoxic responses following exposure to human macrophages. Clois30B, with a quaternary ammonium tallow coating, induced a robust cell membrane damage and pyroptosis effect which was eliminated after incineration. Conversely, incinerated nanoclay exposure primarily caused elevated inflammatory cytokine release from THP-1 cells. Collectively, pre-incinerated nanoclay displayed interaction with macrophage membrane components (molecular initiating event), increased pro-inflammatory mediators, and increased inflammatory cell recruitment (two key events) in the lun","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"16"},"PeriodicalIF":7.2,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175874","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}
Pub Date : 2024-03-11DOI: 10.1186/s12989-024-00576-8
Eva C. M. Vitucci, Alysha E. Simmons, Elizabeth M. Martin, Shaun D. McCullough
Particulate matter 2.5 (PM2.5) deposition in the lung’s alveolar capillary region (ACR) is significantly associated with respiratory disease development, yet the molecular mechanisms are not completely understood. Adverse responses that promote respiratory disease development involve orchestrated, intercellular signaling between multiple cell types within the ACR. We investigated the molecular mechanisms elicited in response to PM2.5 deposition in the ACR, in an in vitro model that enables intercellular communication between multiple resident cell types of the ACR. An in vitro, tri-culture model of the ACR, incorporating alveolar-like epithelial cells (NCI-H441), pulmonary fibroblasts (IMR90), and pulmonary microvascular endothelial cells (HULEC) was developed to investigate cell type-specific molecular responses to a PM2.5 exposure in an in-vivo-like model. This tri-culture in vitro model was termed the alveolar capillary region exposure (ACRE) model. Alveolar epithelial cells in the ACRE model were exposed to a suspension of diesel exhaust particulates (DEP) (20 µg/cm2) with an average diameter of 2.5 µm. Alveolar epithelial barrier formation, and transcriptional and protein expression alterations in the directly exposed alveolar epithelial and the underlying endothelial cells were investigated over a 24 h DEP exposure. Alveolar epithelial barrier formation was not perturbed by the 24 h DEP exposure. Despite no alteration in barrier formation, we demonstrate that alveolar epithelial DEP exposure induces transcriptional and protein changes in both the alveolar epithelial cells and the underlying microvascular endothelial cells. Specifically, we show that the underlying microvascular endothelial cells develop redox dysfunction and increase proinflammatory cytokine secretion. Furthermore, we demonstrate that alveolar epithelial MAPK signaling modulates the activation of NRF2 and IL-8 secretion in the underlying microvascular endothelial cells. Endothelial redox dysfunction and increased proinflammatory cytokine secretion are two common events in respiratory disease development. These findings highlight new, cell-type specific roles of the alveolar epithelium and microvascular endothelium in the ACR in respiratory disease development following PM2.5 exposure. Ultimately, these data expand our current understanding of respiratory disease development following particle exposures and illustrate the utility of multicellular in vitro systems for investigating respiratory tract health.
{"title":"Epithelial MAPK signaling directs endothelial NRF2 signaling and IL-8 secretion in a tri-culture model of the alveolar-microvascular interface following diesel exhaust particulate (DEP) exposure","authors":"Eva C. M. Vitucci, Alysha E. Simmons, Elizabeth M. Martin, Shaun D. McCullough","doi":"10.1186/s12989-024-00576-8","DOIUrl":"https://doi.org/10.1186/s12989-024-00576-8","url":null,"abstract":"Particulate matter 2.5 (PM2.5) deposition in the lung’s alveolar capillary region (ACR) is significantly associated with respiratory disease development, yet the molecular mechanisms are not completely understood. Adverse responses that promote respiratory disease development involve orchestrated, intercellular signaling between multiple cell types within the ACR. We investigated the molecular mechanisms elicited in response to PM2.5 deposition in the ACR, in an in vitro model that enables intercellular communication between multiple resident cell types of the ACR. An in vitro, tri-culture model of the ACR, incorporating alveolar-like epithelial cells (NCI-H441), pulmonary fibroblasts (IMR90), and pulmonary microvascular endothelial cells (HULEC) was developed to investigate cell type-specific molecular responses to a PM2.5 exposure in an in-vivo-like model. This tri-culture in vitro model was termed the alveolar capillary region exposure (ACRE) model. Alveolar epithelial cells in the ACRE model were exposed to a suspension of diesel exhaust particulates (DEP) (20 µg/cm2) with an average diameter of 2.5 µm. Alveolar epithelial barrier formation, and transcriptional and protein expression alterations in the directly exposed alveolar epithelial and the underlying endothelial cells were investigated over a 24 h DEP exposure. Alveolar epithelial barrier formation was not perturbed by the 24 h DEP exposure. Despite no alteration in barrier formation, we demonstrate that alveolar epithelial DEP exposure induces transcriptional and protein changes in both the alveolar epithelial cells and the underlying microvascular endothelial cells. Specifically, we show that the underlying microvascular endothelial cells develop redox dysfunction and increase proinflammatory cytokine secretion. Furthermore, we demonstrate that alveolar epithelial MAPK signaling modulates the activation of NRF2 and IL-8 secretion in the underlying microvascular endothelial cells. Endothelial redox dysfunction and increased proinflammatory cytokine secretion are two common events in respiratory disease development. These findings highlight new, cell-type specific roles of the alveolar epithelium and microvascular endothelium in the ACR in respiratory disease development following PM2.5 exposure. Ultimately, these data expand our current understanding of respiratory disease development following particle exposures and illustrate the utility of multicellular in vitro systems for investigating respiratory tract health.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"16 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097590","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}
Pub Date : 2024-03-08DOI: 10.1186/s12989-024-00575-9
Aiman Abzhanova, Jon Berntsen, Edward R Pennington, Lisa Dailey, Syed Masood, Ingrid George, Nina Warren, Joseph Martin, Michael D Hays, Andrew J Ghio, Jason P Weinstein, Yong Ho Kim, Earl Puckett, James M Samet
Wildland fires contribute significantly to the ambient air pollution burden worldwide, causing a range of adverse health effects in exposed populations. The toxicity of woodsmoke, a complex mixture of gases, volatile organic compounds, and particulate matter, is commonly studied in vitro using isolated exposures of conventionally cultured lung cells to either resuspended particulate matter or organic solvent extracts of smoke, leading to incomplete toxicity evaluations. This study aimed to improve our understanding of the effects of woodsmoke inhalation by building an advanced in vitro exposure system that emulates human exposure of the airway epithelium. We report the development and characterization of an innovative system that permits live-cell monitoring of the intracellular redox status of differentiated primary human bronchial epithelial cells cultured at an air-liquid interface (pHBEC-ALI) as they are exposed to unfractionated woodsmoke generated in a tube furnace in real time. pHBEC-ALI exposed to freshly generated woodsmoke showed oxidative changes that were dose-dependent and reversible, and not attributable to carbon monoxide exposure. These findings show the utility of this novel system for studying the molecular initiating events underlying woodsmoke-induced toxicity in a physiologically relevant in vitro model, and its potential to provide biological plausibility for risk assessment and public health measures.
{"title":"Monitoring redox stress in human airway epithelial cells exposed to woodsmoke at an air-liquid interface.","authors":"Aiman Abzhanova, Jon Berntsen, Edward R Pennington, Lisa Dailey, Syed Masood, Ingrid George, Nina Warren, Joseph Martin, Michael D Hays, Andrew J Ghio, Jason P Weinstein, Yong Ho Kim, Earl Puckett, James M Samet","doi":"10.1186/s12989-024-00575-9","DOIUrl":"10.1186/s12989-024-00575-9","url":null,"abstract":"<p><p>Wildland fires contribute significantly to the ambient air pollution burden worldwide, causing a range of adverse health effects in exposed populations. The toxicity of woodsmoke, a complex mixture of gases, volatile organic compounds, and particulate matter, is commonly studied in vitro using isolated exposures of conventionally cultured lung cells to either resuspended particulate matter or organic solvent extracts of smoke, leading to incomplete toxicity evaluations. This study aimed to improve our understanding of the effects of woodsmoke inhalation by building an advanced in vitro exposure system that emulates human exposure of the airway epithelium. We report the development and characterization of an innovative system that permits live-cell monitoring of the intracellular redox status of differentiated primary human bronchial epithelial cells cultured at an air-liquid interface (pHBEC-ALI) as they are exposed to unfractionated woodsmoke generated in a tube furnace in real time. pHBEC-ALI exposed to freshly generated woodsmoke showed oxidative changes that were dose-dependent and reversible, and not attributable to carbon monoxide exposure. These findings show the utility of this novel system for studying the molecular initiating events underlying woodsmoke-induced toxicity in a physiologically relevant in vitro model, and its potential to provide biological plausibility for risk assessment and public health measures.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"14"},"PeriodicalIF":7.2,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10921608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065632","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}
With rapid increase in the global use of various plastics, microplastics (MPs) and nanoplastics (NPs) pollution and their adverse health effects have attracted global attention. MPs have been detected out in human body and both MPs and NPs showed female reproductive toxicological effects in animal models. Miscarriage (abnormal early embryo loss), accounting for 15-25% pregnant women worldwide, greatly harms human reproduction. However, the adverse effects of NPs on miscarriage have never been explored. In this study, we identified that polystyrene (PS) plastics particles were present in women villous tissues. Their levels were higher in villous tissues of unexplained recurrent miscarriage (RM) patients vs. healthy control (HC) group. Furthermore, mouse assays further confirmed that exposure to polystyrene nanoplastics (PS-NPs, 50 nm in diameter, 50 or 100 mg/kg) indeed induced miscarriage. In mechanism, PS-NPs exposure (50, 100, 150, or 200 µg/mL) increased oxidative stress, decreased mitochondrial membrane potential, and increased apoptosis in human trophoblast cells by activating Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3 signaling through mitochondrial pathway. The alteration in this signaling was consistent in placental tissues of PS-NPs-exposed mouse model and in villous tissues of unexplained RM patients. Supplement with Bcl-2 could efficiently suppress apoptosis in PS-NPs-exposed trophoblast cells and reduce apoptosis and alleviate miscarriage in PS-NPs-exposed pregnant mouse model. Exposure to PS-NPs activated Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3, leading to excessive apoptosis in human trophoblast cells and in mice placental tissues, further inducing miscarriage.
{"title":"Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage","authors":"Shukun Wan, Xiaoqing Wang, Weina Chen, Manli Wang, Jingsong Zhao, Zhongyan Xu, Rong Wang, Chenyang Mi, Zhaodian Zheng, Huidong Zhang","doi":"10.1186/s12989-024-00574-w","DOIUrl":"https://doi.org/10.1186/s12989-024-00574-w","url":null,"abstract":"With rapid increase in the global use of various plastics, microplastics (MPs) and nanoplastics (NPs) pollution and their adverse health effects have attracted global attention. MPs have been detected out in human body and both MPs and NPs showed female reproductive toxicological effects in animal models. Miscarriage (abnormal early embryo loss), accounting for 15-25% pregnant women worldwide, greatly harms human reproduction. However, the adverse effects of NPs on miscarriage have never been explored. In this study, we identified that polystyrene (PS) plastics particles were present in women villous tissues. Their levels were higher in villous tissues of unexplained recurrent miscarriage (RM) patients vs. healthy control (HC) group. Furthermore, mouse assays further confirmed that exposure to polystyrene nanoplastics (PS-NPs, 50 nm in diameter, 50 or 100 mg/kg) indeed induced miscarriage. In mechanism, PS-NPs exposure (50, 100, 150, or 200 µg/mL) increased oxidative stress, decreased mitochondrial membrane potential, and increased apoptosis in human trophoblast cells by activating Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3 signaling through mitochondrial pathway. The alteration in this signaling was consistent in placental tissues of PS-NPs-exposed mouse model and in villous tissues of unexplained RM patients. Supplement with Bcl-2 could efficiently suppress apoptosis in PS-NPs-exposed trophoblast cells and reduce apoptosis and alleviate miscarriage in PS-NPs-exposed pregnant mouse model. Exposure to PS-NPs activated Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3, leading to excessive apoptosis in human trophoblast cells and in mice placental tissues, further inducing miscarriage. ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"5 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054687","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}
Pub Date : 2024-03-07DOI: 10.1186/s12989-024-00568-8
Xiaofeng Qin, Zhiyuan Niu, Hui Chen, Yongbin Hu
Chronic inflammation and fibrosis are characteristics of silicosis, and the inflammatory mediators involved in silicosis have not been fully elucidated. Recently, macrophage-derived exosomes have been reported to be inflammatory modulators, but their role in silicosis has not been explored. The purpose of the present study was to investigate the role of macrophage-derived exosomal high mobility group box 3 (HMGB3) in silica-induced pulmonary inflammation. The induction of the inflammatory response and the recruitment of monocytes/macrophages were evaluated by immunofluorescence, flow cytometry and transwell assays. The expression of inflammatory cytokines was examined by RT–PCR and ELISA, and the signalling pathways involved were examined by western blot analysis. HMGB3 expression was increased in exosomes derived from silica-exposed macrophages. Exosomal HMGB3 significantly upregulated the expression of inflammatory cytokines, activated the STAT3/MAPK (ERK1/2 and p38)/NF-κB pathways in monocytes/macrophages, and promoted the migration of these cells by CCR2. Exosomal HMGB3 is a proinflammatory modulator of silica-induced inflammation that promotes the inflammatory response and recruitment of monocytes/macrophages by regulating the activation of the STAT3/MAPK/NF-κB/CCR2 pathways.
{"title":"Macrophage-derived exosomal HMGB3 regulates silica-induced pulmonary inflammation by promoting M1 macrophage polarization and recruitment","authors":"Xiaofeng Qin, Zhiyuan Niu, Hui Chen, Yongbin Hu","doi":"10.1186/s12989-024-00568-8","DOIUrl":"https://doi.org/10.1186/s12989-024-00568-8","url":null,"abstract":"Chronic inflammation and fibrosis are characteristics of silicosis, and the inflammatory mediators involved in silicosis have not been fully elucidated. Recently, macrophage-derived exosomes have been reported to be inflammatory modulators, but their role in silicosis has not been explored. The purpose of the present study was to investigate the role of macrophage-derived exosomal high mobility group box 3 (HMGB3) in silica-induced pulmonary inflammation. The induction of the inflammatory response and the recruitment of monocytes/macrophages were evaluated by immunofluorescence, flow cytometry and transwell assays. The expression of inflammatory cytokines was examined by RT–PCR and ELISA, and the signalling pathways involved were examined by western blot analysis. HMGB3 expression was increased in exosomes derived from silica-exposed macrophages. Exosomal HMGB3 significantly upregulated the expression of inflammatory cytokines, activated the STAT3/MAPK (ERK1/2 and p38)/NF-κB pathways in monocytes/macrophages, and promoted the migration of these cells by CCR2. Exosomal HMGB3 is a proinflammatory modulator of silica-induced inflammation that promotes the inflammatory response and recruitment of monocytes/macrophages by regulating the activation of the STAT3/MAPK/NF-κB/CCR2 pathways.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"61 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054539","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}
Pub Date : 2024-03-06DOI: 10.1186/s12989-024-00570-0
Caroline Carlé, Delphine Boucher, Luisa Morelli, Camille Larue, Ekaterina Ovtchinnikova, Louise Battut, Kawthar Boumessid, Melvin Airaud, Muriel Quaranta-Nicaise, Jean-Luc Ravanat, Gilles Dietrich, Sandrine Menard, Gérard Eberl, Nicolas Barnich, Emmanuel Mas, Marie Carriere, Ziad Al Nabhani, Frédérick Barreau
<p><b>Correction: Particle and Fibre Toxicology (2023) 20:45</b><b>https://doi.org/10.1186/s12989-023-00555-5</b></p><p>Following publication of the original article [1], the authors reported some spelling and bibliograph errors. Below is a table of corrections which have been implemented in the original article.</p><p>The original article [1] has been corrected.</p><table><thead><tr><th><p>Section</p></th><th><p>Originally published text</p></th><th><p>Corrected text</p></th></tr></thead><tbody><tr><td><p>Abstract</p></td><td><p>Perinatal exposure to titanium dioxide (TiO<sub>2</sub>), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel disease (IBD) later in life</p></td><td><p>Perinatal exposure to titanium dioxide (TiO<sub>2</sub>), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel diseases (IBD) later in life</p></td></tr><tr><td><p>Background</p></td><td><p>A significant number of human chronic diseases (inflammatory, metabolic …) is linked to a deficiency of the IBF and some of them, like IBD, exhibit alterations of the four IBF’s compartments [8, 9]</p></td><td><p>significant number of human chronic diseases (inflammatory, metabolic …) is linked to a deficiency of the IBF and some of them, like IBD, exhibit alterations of the three IBF’s compartments [8, 9]</p></td></tr><tr><td> </td><td><p>To evaluate this hypothesis, we exposed pregnant female C57BL/6 mice to 9 mg E171/kg b.w./day via their drinking water,from the beginning of gestation until 3 weeks postdelivery</p></td><td><p>To evaluate this hypothesis, we exposed pregnant female C57BL/6 mice to 9 mg E171/kg b.w./day via their drinking water, from the beginning of gestation until 4 weeks postdelivery</p></td></tr><tr><td> </td><td><p>This exposure concentration is in the lower range of the estimated daily exposure of human adults, which ranges between 5.5 and 10.4 mg/kg b.w./day according to EFSA’s estimations [ref 35]</p></td><td><p>This exposure concentration is in the lower range of the estimated daily exposure of human adults, which ranges between 5.5 and 10.4 mg/kg b.w./day according to EFSA’s estimations [29]</p></td></tr><tr><td> </td><td><p>When considering the guidances on dose conversion between human and animal exposure, such as the Nair and Jacob practice guide or FDA’s guidelines, we previously estimated that doses up to 50–60 mg/kg b.w./day in mice would be realistic [ref notre revue PFT] confirming that the dose used in the present study can be considered as a low exposure dose</p></td><td><p>When considering the guidances on dose conversion between human and animal exposure, such as the Nair and Jacob practice guide or FDA’s guidelines, we previously estimated that doses up to 50–60 mg/kg b.w./day in mice would be realistic [14] confirming that the dose used in the present study can be considered as a low exposure dose</p></
更正：Particle and Fibre Toxicology (2023) 20:45https://doi.org/10.1186/s12989-023-00555-5Following 原文[1]发表后，作者报告了一些拼写和文献错误。以下是原文[1]的更正表。节最初发表的文本更正后的文本摘要作为食源性微粒的二氧化钛（TiO2）的产前暴露可能会影响肠道屏障功能和日后患炎症性肠病（IBD）的易感性作为食源性微粒的二氧化钛（TiO2）的产前暴露可能会影响肠道屏障功能和日后患炎症性肠病（IBD）的易感性背景大量人类慢性疾病（炎症性、代谢性......）与肠道屏障功能缺乏有关。为了评估这一假设，我们通过饮用水向怀孕的雌性 C57BL/6 小鼠暴露 9 mg E171/kg b. w./天。w./day via their drinking water,from the beginning of pregnancy until 3 weeks postdelivery.根据欧洲食品安全局（EFSA）的估计，这一暴露浓度处于人类成人每日暴露量的较低范围，即介于 5.5 至 10.4 毫克/千克体重/天之间[参考文献 35]。根据欧洲食品安全局的估计，这一暴露浓度处于人类成人每日暴露量估计值的较低范围，在 5.5 至 10.4 毫克/千克体重/天之间。当考虑到人类和动物暴露剂量换算指南（如 Nair 和 Jacob 实践指南或 FDA 指南）时，我们之前估计小鼠体内的剂量最高可达 50-60 mg/kg b. w. /day [ref notre revue PFT]，这证实本研究中使用的剂量可被视为低暴露剂量。结果图 1 食源性二氧化钛通过人体屏障转移的能力。A-G 野生型雌性小鼠暴露于二氧化钛（9 毫克/体重/天）图 1 食源性二氧化钛在人体屏障中的迁移能力。A-G 野生型雌性小鼠暴露于 TiO2（9 毫克/千克体重/天） 由于肠道微生物群被描述为调节肠道上皮细胞的稳态[29, 30]，我们研究了围产期暴露于食源性 TiO2 是否会影响肠道上皮细胞的稳态[30, 31]、图 2 小鼠围产期暴露于食源性 TiO2 30 天后对结肠微生物群的影响。A-E 野生型雌性小鼠在围产期（包括妊娠期和哺乳期）暴露于二氧化钛（9 毫克/体重/天）。然后在出生后第 30 天图 2 围产期暴露于食源性 TiO2 对出生后第 30 天结肠微生物区系的影响。A-D 野生型雌性小鼠在围产期（包括妊娠期和哺乳期）暴露于二氧化钛（9 毫克/千克体重/天）。出生后第 30 天，幼鼠被处死，并通过 16S rRNA 基因测序监测结肠粘膜相关微生物区系的结构（B-D）C-D 出生后第 30 天，暴露或未暴露于食源性 TiV 的小鼠结肠微生物区系的组成（C）和受显著干扰的细菌属的折叠变化 2（D）。S5A，B）在出生后 50 天，暴露于 TiO2 只增加了 Muc2 的水平（附加文件 5：图 5）。
{"title":"Correction: Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life","authors":"Caroline Carlé, Delphine Boucher, Luisa Morelli, Camille Larue, Ekaterina Ovtchinnikova, Louise Battut, Kawthar Boumessid, Melvin Airaud, Muriel Quaranta-Nicaise, Jean-Luc Ravanat, Gilles Dietrich, Sandrine Menard, Gérard Eberl, Nicolas Barnich, Emmanuel Mas, Marie Carriere, Ziad Al Nabhani, Frédérick Barreau","doi":"10.1186/s12989-024-00570-0","DOIUrl":"https://doi.org/10.1186/s12989-024-00570-0","url":null,"abstract":"<p><b>Correction: Particle and Fibre Toxicology (2023) 20:45</b><b>https://doi.org/10.1186/s12989-023-00555-5</b></p><p>Following publication of the original article [1], the authors reported some spelling and bibliograph errors. Below is a table of corrections which have been implemented in the original article.</p><p>The original article [1] has been corrected.</p><table><thead><tr><th><p>Section</p></th><th><p>Originally published text</p></th><th><p>Corrected text</p></th></tr></thead><tbody><tr><td><p>Abstract</p></td><td><p>Perinatal exposure to titanium dioxide (TiO<sub>2</sub>), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel disease (IBD) later in life</p></td><td><p>Perinatal exposure to titanium dioxide (TiO<sub>2</sub>), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel diseases (IBD) later in life</p></td></tr><tr><td><p>Background</p></td><td><p>A significant number of human chronic diseases (inflammatory, metabolic …) is linked to a deficiency of the IBF and some of them, like IBD, exhibit alterations of the four IBF’s compartments [8, 9]</p></td><td><p>significant number of human chronic diseases (inflammatory, metabolic …) is linked to a deficiency of the IBF and some of them, like IBD, exhibit alterations of the three IBF’s compartments [8, 9]</p></td></tr><tr><td> </td><td><p>To evaluate this hypothesis, we exposed pregnant female C57BL/6 mice to 9 mg E171/kg b.w./day via their drinking water,from the beginning of gestation until 3 weeks postdelivery</p></td><td><p>To evaluate this hypothesis, we exposed pregnant female C57BL/6 mice to 9 mg E171/kg b.w./day via their drinking water, from the beginning of gestation until 4 weeks postdelivery</p></td></tr><tr><td> </td><td><p>This exposure concentration is in the lower range of the estimated daily exposure of human adults, which ranges between 5.5 and 10.4 mg/kg b.w./day according to EFSA’s estimations [ref 35]</p></td><td><p>This exposure concentration is in the lower range of the estimated daily exposure of human adults, which ranges between 5.5 and 10.4 mg/kg b.w./day according to EFSA’s estimations [29]</p></td></tr><tr><td> </td><td><p>When considering the guidances on dose conversion between human and animal exposure, such as the Nair and Jacob practice guide or FDA’s guidelines, we previously estimated that doses up to 50–60 mg/kg b.w./day in mice would be realistic [ref notre revue PFT] confirming that the dose used in the present study can be considered as a low exposure dose</p></td><td><p>When considering the guidances on dose conversion between human and animal exposure, such as the Nair and Jacob practice guide or FDA’s guidelines, we previously estimated that doses up to 50–60 mg/kg b.w./day in mice would be realistic [14] confirming that the dose used in the present study can be considered as a low exposure dose</p></","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"27 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140046630","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}
Pub Date : 2024-03-01DOI: 10.1186/s12989-024-00573-x
Laura Morin, Valérie Lecureur, Alain Lescoat
Crystalline silica (cSiO2) is a mineral found in rocks; workers from the construction or denim industries are particularly exposed to cSiO2 through inhalation. cSiO2 inhalation increases the risk of silicosis and systemic autoimmune diseases. Inhaled cSiO2 microparticles can reach the alveoli where they induce inflammation, cell death, auto-immunity and fibrosis but the specific molecular pathways involved in these cSiO2 effects remain unclear. This systematic review aims to provide a comprehensive state of the art on omic approaches and exposure models used to study the effects of inhaled cSiO2 in mice and rats and to highlight key results from omic data in rodents also validated in human. The protocol of systematic review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible articles were identified in PubMed, Embase and Web of Science. The search strategy included original articles published after 1990 and written in English which included mouse or rat models exposed to cSiO2 and utilized omic approaches to identify pathways modulated by cSiO2. Data were extracted and quality assessment was based on the SYRCLE’s Risk of Bias tool for animal studies. Rats and male rodents were the more used models while female rodents and autoimmune prone models were less studied. Exposure of animals were both acute and chronic and the timing of outcome measurement through omics approaches were homogeneously distributed. Transcriptomic techniques were more commonly performed while proteomic, metabolomic and single-cell omic methods were less utilized. Immunity and inflammation were the main domains modified by cSiO2 exposure in lungs of mice and rats. Less than 20% of the results obtained in rodents were finally verified in humans. Omic technics offer new insights on the effects of cSiO2 exposure in mice and rats although the majority of data still need to be validated in humans. Autoimmune prone model should be better characterised and systemic effects of cSiO2 need to be further studied to better understand cSiO2-induced autoimmunity. Single-cell omics should be performed to inform on pathological processes induced by cSiO2 exposure.
晶体二氧化硅（cSiO2）是一种存在于岩石中的矿物质；建筑或牛仔布行业的工人尤其容易通过吸入而接触到二氧化硅。吸入的二氧化硅微粒可进入肺泡，诱发炎症、细胞死亡、自身免疫和纤维化，但二氧化硅产生这些影响的具体分子途径仍不清楚。本系统综述旨在全面介绍用于研究小鼠和大鼠吸入的二氧化硅影响的奥米克方法和暴露模型的最新进展，并重点介绍在啮齿类动物中得到验证的奥米克数据的关键结果。系统综述方案遵循 PRISMA（系统综述和元分析首选报告项目）指南。符合条件的文章在 PubMed、Embase 和 Web of Science 中进行了搜索。搜索策略包括1990年后发表的英文原创文章，这些文章包括暴露于二氧化硅的小鼠或大鼠模型，并利用欧米克方法确定二氧化硅调节的途径。根据SYRCLE的动物研究偏倚风险工具提取数据并进行质量评估。大鼠和雄性啮齿类动物是使用较多的模型，而雌性啮齿类动物和自身免疫易感模型的研究较少。动物的暴露既有急性的，也有慢性的，通过 omics 方法测量结果的时间分布也很均匀。转录组技术更常用，而蛋白质组、代谢组和单细胞全息方法则较少使用。免疫和炎症是小鼠和大鼠肺部因接触二氧化硅而改变的主要领域。在啮齿动物身上获得的结果只有不到20%最终在人类身上得到了验证。尽管大部分数据仍需在人体中验证，但海洋学技术为了解小鼠和大鼠接触二氧化硅的影响提供了新的视角。应更好地描述易发生自身免疫的模型，并进一步研究二氧化硅的全身效应，以更好地了解二氧化硅诱导的自身免疫。应进行单细胞组学研究，以了解二氧化硅暴露诱发的病理过程。
{"title":"Results from omic approaches in rat or mouse models exposed to inhaled crystalline silica: a systematic review","authors":"Laura Morin, Valérie Lecureur, Alain Lescoat","doi":"10.1186/s12989-024-00573-x","DOIUrl":"https://doi.org/10.1186/s12989-024-00573-x","url":null,"abstract":"Crystalline silica (cSiO2) is a mineral found in rocks; workers from the construction or denim industries are particularly exposed to cSiO2 through inhalation. cSiO2 inhalation increases the risk of silicosis and systemic autoimmune diseases. Inhaled cSiO2 microparticles can reach the alveoli where they induce inflammation, cell death, auto-immunity and fibrosis but the specific molecular pathways involved in these cSiO2 effects remain unclear. This systematic review aims to provide a comprehensive state of the art on omic approaches and exposure models used to study the effects of inhaled cSiO2 in mice and rats and to highlight key results from omic data in rodents also validated in human. The protocol of systematic review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible articles were identified in PubMed, Embase and Web of Science. The search strategy included original articles published after 1990 and written in English which included mouse or rat models exposed to cSiO2 and utilized omic approaches to identify pathways modulated by cSiO2. Data were extracted and quality assessment was based on the SYRCLE’s Risk of Bias tool for animal studies. Rats and male rodents were the more used models while female rodents and autoimmune prone models were less studied. Exposure of animals were both acute and chronic and the timing of outcome measurement through omics approaches were homogeneously distributed. Transcriptomic techniques were more commonly performed while proteomic, metabolomic and single-cell omic methods were less utilized. Immunity and inflammation were the main domains modified by cSiO2 exposure in lungs of mice and rats. Less than 20% of the results obtained in rodents were finally verified in humans. Omic technics offer new insights on the effects of cSiO2 exposure in mice and rats although the majority of data still need to be validated in humans. Autoimmune prone model should be better characterised and systemic effects of cSiO2 need to be further studied to better understand cSiO2-induced autoimmunity. Single-cell omics should be performed to inform on pathological processes induced by cSiO2 exposure.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"5 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140008100","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}
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