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Article ; Online: Development and validation of a human bronchial epithelial spheroid model to study respiratory toxicity in vitro.

Celis, Thomas / Bullens, Dominique M A / Hoet, Peter H M / Ghosh, Manosij

2023 Volume 98, Issue 2, Page(s) 493–505

Abstract: The use of laboratory animals in research has been extensively criticized. While most of the critique has been centered around the ethical aspect, also the economic and scientific aspects have been frequently mentioned as points of concern. As a result, ... ...

Abstract	The use of laboratory animals in research has been extensively criticized. While most of the critique has been centered around the ethical aspect, also the economic and scientific aspects have been frequently mentioned as points of concern. As a result, the use of alternative methods has gradually become more enticing. The most used alternatives to laboratory animals are the 2D monolayer cell cultures. However, the limited translatability of these monolayer cell cultures to in vivo has led to the development of 3D cell cultures that are believed to better capture the in vivo physiology and pathology. Here we report on the development of a physiologically more relevant 3D cell model (spheroids) comprised of human bronchial epithelial (16HBE14o-) cells, for use in respiratory toxicity research. Culturing 16HBE14o-cells as hanging-drops led to the formation of stable spheroids which showed an increased expression of CLDN1 when compared to 2D monolayer cultured cells. In addition, cell-cycle analysis revealed an increased sub-G0 population and signs of G0/G1 arrest in spheroids. Afterwards, standard operating procedures (SOPs) were established, and existing protocols optimized, for compatibility with spheroids. Spheroids were successfully used to assess cytotoxicity, genotoxicity, apoptosis/necrosis, and oxidative stress after exposure to known cytotoxic or genotoxic compounds. The development of the bronchial epithelial spheroids and the establishment of SOPs can contribute to a more reliable toxicity assessment of chemicals and may aid in bridging the gap between in vivo and in vitro experiments.
MeSH term(s)	Animals ; Humans ; Spheroids, Cellular ; Cells, Cultured ; Cell Culture Techniques/methods ; Antineoplastic Agents
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2023-12-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-023-03619-9
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Article ; Online: Assessment of Experimental Techniques That Facilitate Human Granuloma Formation in an In Vitro System: A Systematic Review.

Ganesan, Nirosha / Ronsmans, Steven / Vanoirbeek, Jeroen / Hoet, Peter H M

Cells

2022 Volume 11, Issue 5

Abstract: The process of granuloma formation is complex, and due to species differences, the validity of animal studies is somewhat questioned. Moreover, the large number of animals needed to observe the different stages of development also raises ethical ... ...

Abstract	The process of granuloma formation is complex, and due to species differences, the validity of animal studies is somewhat questioned. Moreover, the large number of animals needed to observe the different stages of development also raises ethical questions. Therefore, researchers have explored the use of human peripheral blood mononuclear cells (PBMCs), a heterogeneous population of immune cells, in an in vitro model. This review included in vitro studies that focused on exposing PBMCs-from healthy, sensitized, or diseased individuals-to antigens derived from infectious agents-such as mycobacteria or
MeSH term(s)	Animals ; Granuloma/pathology ; Humans ; Leukocytes, Mononuclear
Language	English
Publishing date	2022-03-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11050864
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Article ; Online: Neurotoxicity of four frequently used nanoparticles: a systematic review to reveal the missing data.

Gong, Jia-You / Holt, Matthew G / Hoet, Peter H M / Ghosh, Manosij

Archives of toxicology

2022 Volume 96, Issue 5, Page(s) 1141–1212

Abstract: Systemic exposure to nanoparticles (NPs) adversely affects different organs, including the nervous system. We systematically extracted data from publication on PubMed and Embase database up to the year 2020, and analyzed in vitro and in vivo ... ...

Abstract	Systemic exposure to nanoparticles (NPs) adversely affects different organs, including the nervous system. We systematically extracted data from publication on PubMed and Embase database up to the year 2020, and analyzed in vitro and in vivo neurotoxicity of 4 of the most well studied NPs (silver NPs, carbon-based NPs, iron NPs and silica NPs). A relatively good correlation was observed between in vitro and in vivo effects, including genotoxicity, oxidative stress, apoptosis and pro-inflammatory effects. However, crucial knowledge gap exists in current understanding of the underlying mechanisms. Some of the critical knowledge gaps and research needs identified in relation to neurotoxicity of nanoparticles include (1) lack of physio-chemical characteristics of NPs used, (2) cellular/tissue uptake of NP, (3) NP translocation across the blood-brain barrier (BBB), (4) Effect of exposure routes.
MeSH term(s)	Blood-Brain Barrier ; Humans ; Metal Nanoparticles/toxicity ; Nanoparticles/toxicity ; Neurotoxicity Syndromes/etiology ; Oxidative Stress ; Silicon Dioxide
Chemical Substances	Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2022-03-12
Publishing country	Germany
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-022-03233-1
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Article ; Online: Sampling strategies and analytical techniques for assessment of airborne micro and nano plastics

Azari, Aala / Vanoirbeek, Jeroen A.J. / Van Belleghem, Frank / Vleeschouwers, Brent / Hoet, Peter H.M. / Ghosh, Manosij

Environment International. 2023 Apr., v. 174 p.107885-

2023

Abstract: The atmosphere is pervasively polluted by microplastics and nano plastics (M/NPs) released into indoor and outdoor areas. However, various methodologies and their limitations along with non-standardization make the comparison of information concerning ... ...

Abstract	The atmosphere is pervasively polluted by microplastics and nano plastics (M/NPs) released into indoor and outdoor areas. However, various methodologies and their limitations along with non-standardization make the comparison of information concerning their prevalence difficult. Such diversity in techniques greatly limits the interpretation of results. Herein, We extracted data from publications on PubMed and Embase database up to the year 2022 regarding sampling strategies, identification methods, and reporting data for M/NPs quantification. In this review, 5 major areas for measuring airborne M/NPs have been identified including pre-sampling/ sampling/ post-sampling/ analysis/ and contamination avoidance. There are many challenges specific to each of those sections that need to be resolved through further method development and harmonization. This review mainly focuses on the different methods for collecting atmospheric M/NPs and also the analytical tools which have been used for their identification. While passive sampling is the most user-friendly method, the most precise and reproducible approach for collecting plastic particles is an active method which is directly followed by visual counting as the most common physical analysis technique. Polymers collected using visual sorting are most frequently identified by spectroscopy (FTIR; Raman). However, destructive analytical techniques (thermal degradation) also provide precise chemical information. In all cases, the methods were screened for advantages, limitations, and fieldwork abilities. This review outlines and critiques knowledge gaps, and recommendations to support standardized and comparable future research.
Keywords	databases ; environment ; microplastics ; spectroscopy ; thermal degradation ; Nano plastics ; Atmosphere ; Analytical methods ; a.s.L. ; CaF2 ; C/O ; FTIR ; HQI ; LOD ; MRs ; MP ; µFT-IR ; NP ; PLM ; PA ; PEST ; PE ; PET ; PP ; PS ; PTEF ; PVC ; Pyr-GC/MS ; RH ; S&S ; SEM ; SEM-EDX ; TED-GC/MS ; TGA-GC/MS ; v/v ; w/w ; ZnSe
Language	English
Dates of publication	2023-04
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.107885
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Occupational Asthma Caused by Low-Molecular-Weight Chemicals Associated With Contact Dermatitis: A Retrospective Study.

Tsui, Hung-Chang / Ronsmans, Steven / Hoet, Peter H M / Nemery, Benoit / Vanoirbeek, Jeroen A J

The journal of allergy and clinical immunology. In practice

2022 Volume 10, Issue 9, Page(s) 2346–2354.e4

Abstract: Background: Occupational asthma (OA) may have different etiologies, but it is not clear whether the etiologic agents influence the clinical presentation, especially the co-occurrence of skin lesions.: Objective: To determine the impact of different ... ...

Abstract	Background: Occupational asthma (OA) may have different etiologies, but it is not clear whether the etiologic agents influence the clinical presentation, especially the co-occurrence of skin lesions. Objective: To determine the impact of different asthmagens on the characteristics of OA, with a focus on the occurrence of prior or concomitant skin disorders. Methods: In a retrospective analysis of patients who visited the Occupational and Environmental Disease Clinic of a tertiary referral hospital from 2009 to 2019, we classified patients into definite, probable, or possible OA according to prespecified diagnostic guidelines. In multivariate logistic regression with sensitivity analysis, we examined the relation of high- and low-molecular-weight (HMW and LMW) agents with the clinical presentation. Results: Of 209 cases of OA, 66 were caused by HMW agents and 143 by LMW agents. Patients with OA exposed to LMW agents had higher odds of having (had) allergic contact dermatitis (odds ratio, 5.45 [1.80-23.70]; P < .01), compared with patients exposed to HMW agents. Conversely, HMW agents were associated with higher odds of rhinitis symptoms (odds ratio of LMW/HMW, 0.33 [0.17-0.63]; P < .001) and high total IgE (odds ratio of LMW/HMW, 0.35 [0.17-0.70]; P < .01). Risk factors for having coexisting contact dermatitis included construction work, hairdressing, and exposure to metals or epoxy resins. Conclusions: Among patients with OA, exposure to specific LMW agents was associated with a high frequency of contact dermatitis. Different types of asthmagens within HMW or LMW agents appear to determine the phenotype and comorbidity of OA.
MeSH term(s)	Asthma, Occupational/diagnosis ; Dermatitis, Contact ; Humans ; Molecular Weight ; Occupational Diseases ; Occupational Exposure/adverse effects ; Retrospective Studies
Language	English
Publishing date	2022-05-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2022.05.014
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Article ; Online: Exposure to silicates and systemic autoimmune-related outcomes in rodents: a systematic review.

Janssen, Lisa M F / Ghosh, Manosij / Lemaire, Frauke / Michael Pollard, K / Hoet, Peter H M

Particle and fibre toxicology

2022 Volume 19, Issue 1, Page(s) 4

Abstract: Background: Autoimmunity can result from the interplay between genetic background and effects of environmental and/or occupational exposure to hazardous materials. Several compounds, including silica dust, have been linked with systemic autoimmunity and ...

Abstract	Background: Autoimmunity can result from the interplay between genetic background and effects of environmental and/or occupational exposure to hazardous materials. Several compounds, including silica dust, have been linked with systemic autoimmunity and systemic autoimmune diseases, based on epidemiological evidence. For asbestos, a strong link with systemic autoimmune diseases does not yet exist, however, several studies have documented features of autoimmunity following asbestos exposure. Even so, human studies are limited in their ability to identify and examine isolated exposures, making it difficult to demonstrate causation or to assess pathogenic mechanisms. Therefore, this systematic review examines the existing animal evidence regarding autoimmunity and exposure to silicates (silica and asbestos). Methods: PubMed and EMBASE were systematically searched for peer-reviewed studies examining systemic autoimmune disease-related outcomes after silicate exposure in rodents. Literature databases were searched up to September 2021 for studies written in English and where the full text was available. Search strings were established based on a PECO (Population, Exposure, Comparator, Outcome) format. After title, abstract, and full-text screening, thirty-four studies were identified for further analysis. Quality assessment through ToxR tool and qualitative analysis of the results was performed. Results: Although there was significant heterogeneity in the included studies in terms of exposure protocol and genetic background of the rodent models used, it was noted that both genetic background and exposure to silicates [(crystalline) silica and asbestos] are highly relevant to the development of (sub-) clinical systemic autoimmune disease. Conclusion: Parallels were observed between the findings from the animal (this review) and human (epidemiological) studies, arguing that experimental animal models are valuable tools for examining exacerbation or development of autoimmune disease after silicate exposure. However, genetic background and synergism between exposures should be considered in future studies.
MeSH term(s)	Animals ; Autoimmunity ; Dust ; Occupational Exposure/adverse effects ; Rodentia ; Silicates
Chemical Substances	Dust ; Silicates
Language	English
Publishing date	2022-01-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ZDB-ID	2170936-1
ISSN	1743-8977 ; 1743-8977
ISSN (online)	1743-8977
ISSN	1743-8977
DOI	10.1186/s12989-021-00439-6
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Article ; Online: Sampling strategies and analytical techniques for assessment of airborne micro and nano plastics.

Azari, Aala / Vanoirbeek, Jeroen A J / Van Belleghem, Frank / Vleeschouwers, Brent / Hoet, Peter H M / Ghosh, Manosij

Environment international

2023 Volume 174, Page(s) 107885

Abstract	The atmosphere is pervasively polluted by microplastics and nano plastics (M/NPs) released into indoor and outdoor areas. However, various methodologies and their limitations along with non-standardization make the comparison of information concerning their prevalence difficult. Such diversity in techniques greatly limits the interpretation of results. Herein, We extracted data from publications on PubMed and Embase database up to the year 2022 regarding sampling strategies, identification methods, and reporting data for M/NPs quantification. In this review, 5 major areas for measuring airborne M/NPs have been identified including pre-sampling/ sampling/ post-sampling/ analysis/ and contamination avoidance. There are many challenges specific to each of those sections that need to be resolved through further method development and harmonization. This review mainly focuses on the different methods for collecting atmospheric M/NPs and also the analytical tools which have been used for their identification. While passive sampling is the most user-friendly method, the most precise and reproducible approach for collecting plastic particles is an active method which is directly followed by visual counting as the most common physical analysis technique. Polymers collected using visual sorting are most frequently identified by spectroscopy (FTIR; Raman). However, destructive analytical techniques (thermal degradation) also provide precise chemical information. In all cases, the methods were screened for advantages, limitations, and fieldwork abilities. This review outlines and critiques knowledge gaps, and recommendations to support standardized and comparable future research.
MeSH term(s)	Microplastics ; Plastics ; Water Pollutants, Chemical/analysis ; Environmental Monitoring/methods ; Environment
Chemical Substances	Microplastics ; Plastics ; Water Pollutants, Chemical
Language	English
Publishing date	2023-03-23
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.107885
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Article: Effect of Graphene and Graphene Oxide on Airway Barrier and Differential Phosphorylation of Proteins in Tight and Adherens Junction Pathways.

Van Den Broucke, Sofie / Vanoirbeek, Jeroen A J / Derua, Rita / Hoet, Peter H M / Ghosh, Manosij

Nanomaterials (Basel, Switzerland)

2021 Volume 11, Issue 5

Abstract: Via inhalation we are continuously exposed to environmental and occupational irritants which can induce adverse health effects, such as irritant-induced asthma (IIA). The airway epithelium forms the first barrier encountered by these agents. We ... ...

Abstract	Via inhalation we are continuously exposed to environmental and occupational irritants which can induce adverse health effects, such as irritant-induced asthma (IIA). The airway epithelium forms the first barrier encountered by these agents. We investigated the effect of environmental and occupational irritants on the airway epithelial barrier in vitro. The airway epithelial barrier was mimicked using a coculture model, consisting of bronchial epithelial cells (16HBE) and monocytes (THP-1) seeded on the apical side of a permeable support, and human lung microvascular endothelial cells (HLMVEC) grown on the basal side. Upon exposure to graphene (G) and graphene oxide (GO) in a suspension with fetal calf serum (FCS), ammonium persulfate (AP), sodium persulfate (SP) and hypochlorite (ClO
Language	English
Publishing date	2021-05-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662255-5
ISSN	2079-4991
ISSN	2079-4991
DOI	10.3390/nano11051283
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Article ; Online: Impact of a Polymer-Based Nanoparticle with Formoterol Drug as Nanocarrier System In Vitro and in an Experimental Asthmatic Model.

Bakan, Buket / Jonckheere, Anne-Charlotte / Decaesteker, Tatjana / Marain, Nora F / Murugadoss, Sivakumar / Karabay Yavasoglu, Nefise Ulku / Şahar, Umut / Şenay, Raziye Hilal / Akgöl, Sinan / Göksel, Özlem / Hoet, Peter H M / Vanoirbeek, Jeroen A J

Toxics

2023 Volume 11, Issue 12

Abstract: The implementation of nanotechnology in pulmonary delivery systems might result in better and more specific therapy. Therefore, a nano-sized drug carrier should be toxicologically inert and not induce adverse effects. We aimed to investigate the ... ...

Abstract	The implementation of nanotechnology in pulmonary delivery systems might result in better and more specific therapy. Therefore, a nano-sized drug carrier should be toxicologically inert and not induce adverse effects. We aimed to investigate the responses of a polymer nano drug carrier, a lysine poly-hydroxyethyl methacrylate nanoparticle (NP) [Lys-p(HEMA)], loaded with formoterol, both in vitro and in vivo in an ovalbumin (OVA) asthma model. The successfully synthesized nanodrug formulation showed an expectedly steady in vitro release profile. There was no sign of in vitro toxicity, and the 16HBE and THP-1 cell lines remained vital after exposure to the nanocarrier, both loaded and unloaded. In an experimental asthma model (Balb/c mice) of ovalbumin sensitization and challenge, the nanocarrier loaded and unloaded with formoterol was tested in a preventive strategy and compared to treatment with the drug in a normal formulation. The airway hyperresponsiveness (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL), both cellular and biochemical, were assessed. The application of formoterol as a regular drug and the unloaded and formoterol-loaded NP in OVA-sensitized mice followed by a saline challenge was not different from the control group. Yet, both the NP formulation and the normal drug application led to a more deteriorated lung function and increased lung inflammation in the OVA-sensitized and -challenged mice, showing that the use of the p(HEMA) nanocarrier loaded with formoterol needs more extensive testing before it can be applied in clinical settings.
Language	English
Publishing date	2023-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2733883-6
ISSN	2305-6304 ; 2305-6304
ISSN (online)	2305-6304
ISSN	2305-6304
DOI	10.3390/toxics11120974
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Article ; Online: Synthesis, characterization and toxicity assessment of a new polymeric nanoparticle, l-glutamic acid-g-p(HEMA).

Bakan, Buket / Gülcemal, Süleyman / Akgöl, Sinan / Hoet, Peter H M / Karabay Yavaşoğlu, N Ülkü

Chemico-biological interactions

2019 Volume 315, Page(s) 108870

Abstract: The toxic effects of poly(HEMA)-based polymeric nanoparticles must be analyzed before their biomedical applications as drug delivery systems. The aim of the study was to characterize and evaluate the toxicity for its biocompatibility of a newly ... ...

Abstract	The toxic effects of poly(HEMA)-based polymeric nanoparticles must be analyzed before their biomedical applications as drug delivery systems. The aim of the study was to characterize and evaluate the toxicity for its biocompatibility of a newly synthesized l-glutamic acid-g-p(HEMA) polymeric nanoparticle The nanoparticle was synthesized with surfactant-free emulsion polymerization and grafting techniques. Grafting efficiency was estimated at 58%. The nanoparticle shape was verified as nearly spherical by scanning electron microscopy. Atomic force microscopy images showed a rough surface topography. The nanoparticle had an average size of ~194.6 nm on zeta analysis, and the zeta potential value was -18 mV. Fourier transformed infrared spectroscopy revealed spectra from 750 to 4000 cm
MeSH term(s)	Animals ; Biocompatible Materials/chemistry ; Biocompatible Materials/toxicity ; Cell Line ; Chickens ; Drug Delivery Systems/methods ; Emulsions/chemistry ; Emulsions/pharmacology ; Emulsions/toxicity ; Erythrocytes/drug effects ; Humans ; Methacrylates/chemistry ; Methacrylates/toxicity ; Monocytes/drug effects ; Nanoparticles/chemistry ; Nanoparticles/toxicity ; Particle Size ; Polymers/chemistry ; Polymers/toxicity ; Rabbits ; Salmonella typhimurium/drug effects ; Surface Properties/drug effects ; Surface-Active Agents/chemistry
Chemical Substances	Biocompatible Materials ; Emulsions ; Methacrylates ; Polymers ; Surface-Active Agents ; hydroxyethyl methacrylate (6E1I4IV47V)
Language	English
Publishing date	2019-10-25
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	218799-1
ISSN	1872-7786 ; 0009-2797
ISSN (online)	1872-7786
ISSN	0009-2797
DOI	10.1016/j.cbi.2019.108870
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