147 results on '"Michael Antoniou"'
Search Results
2. Transcriptome analysis of human mammary epithelial cells treated with bisphenol A and bisphenol A analogue mixtures reveals major alterations in multiple cellular pathways
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Robin Mesnage, Helin Omriouate, and Michael Antoniou
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- 2022
3. Automatic Classification of Drones Using Radar: Key Considerations and Performance Evaluation
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Francesco Fioranelli, Mike Newman, Chris Baker, Michael Antoniou, Mohammed Jahangir, Holly Dale, Stephen Harman, Colin Rogers, and Bashar Ahmad
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Automatic target classification is a critical capability for non-cooperative drone surveillance radars in several defence and civilian applications. It is accordingly a well-established research field and numerous algorithms exist for recognising targets, including miniature unmanned air systems (i.e., small, mini, micro and nano platforms), from their radar signatures. They have notably benefited from advances in machine learning (e.g., deep neural networks) and are increasingly able to achieve remarkably high accuracies. Such classification results are often captured by standard, generic, object recognition metrics and originate from testing on simulated or real radar measurements of drones under high signal to noise ratios. Hence, it is difficult to assess and benchmark the performance of different classifiers under realistic operational conditions. In this paper, we first outline the key challenges and considerations associated with the automatic classification of miniature drones from radar data. We then present a set of important performance metrics, from an end-user perspective. They are relevant to typical drone surveillance system requirements and constraints. Selected examples from real radar observations are shown for illustrations. We also outline here various emerging approaches and future directions that can produce more robust drone classifiers for radar.
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- 2023
4. The potential of gene therapy for recessive dystrophic epidermolysis bullosa*
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John A. McGrath, Michael Antoniou, Su M. Lwin, and K S Subramaniam
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medicine.medical_specialty ,Skin Neoplasms ,Heterogeneous group ,integumentary system ,business.industry ,Genetic enhancement ,Mucocutaneous zone ,Genetic Therapy ,Dermatology ,medicine.disease ,Epidermolysis Bullosa Dystrophica ,Dystrophic epidermolysis bullosa ,Skin fragility ,Molecular genetics ,Recessive dystrophic epidermolysis bullosa ,Carcinoma, Squamous Cell ,medicine ,Humans ,Epidermolysis bullosa ,Epidermolysis Bullosa ,business - Abstract
Epidermolysis bullosa (EB) encompasses a heterogeneous group of inherited skin fragility disorders, with mutations in genes encoding the basement membrane zone (BMZ) proteins that normally ensure dermal-epidermal integrity. Of the four main EB types, recessive dystrophic EB (RDEB), especially the severe variant, represents one of the most debilitating clinical entities, with recurrent mucocutaneous blistering and ulceration leading to chronic wounds, infections, inflammation, scarring and ultimately cutaneous squamous cell carcinoma, which leads to premature death. Improved understanding of the molecular genetics of EB over the past three decades and advances in biotechnology have led to rapid progress in developing gene and cell-based regenerative therapies for EB. In particular, RDEB is at the vanguard of advances in human clinical trials of advanced therapeutics. Furthermore, the past decade has witnessed the emergence of a real collective, global effort involving academia and industry, supported by international EB patient organizations such as the Dystrophic Epidermolysis Bullosa Research Association (DEBRA), among others, to develop clinically relevant and marketable targeted therapeutics for EB. Thus, there is an increasing need for the practising dermatologist to become familiar with the concept of gene therapy, fundamental differences between various approaches, and their human applications. This review explains the principles of different approaches of gene therapy, summarizes its journey, and discusses its current and future impact in RDEB.
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- 2022
5. Glyphosate exposure in early pregnancy and reduced fetal growth: a prospective observational study of high-risk pregnancies
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Roy R, Gerona, Jill L, Reiter, Igor, Zakharevich, Cathy, Proctor, Jun, Ying, Robin, Mesnage, Michael, Antoniou, and Paul D, Winchester
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Adult ,Fetal Development ,Pregnancy ,Pregnancy, High-Risk ,Health, Toxicology and Mutagenesis ,Glycine ,Infant, Newborn ,Public Health, Environmental and Occupational Health ,Humans ,Infant ,Female ,Prospective Studies - Abstract
Background Prenatal glyphosate (GLY) exposure is associated with adverse reproductive outcomes in animal studies. Little is known about the effects of GLY exposure during pregnancy in the human population. This study aims to establish baseline urine GLY levels in a high-risk and racially diverse pregnancy cohort and to assess the relationship between prenatal GLY exposure and fetal development and birth outcomes. Methods Random first trimester urine specimens were collected from high risk pregnant women between 2013 and 2016 as part of the Indiana Pregnancy Environmental Exposures Study (PEES). Demographic and clinical data were abstracted from mother and infant medical records. Urine glyphosate levels were measured as a proxy for GLY exposure and quantified using liquid chromatography-tandem mass spectrometry. Primary outcome variables included gestation-adjusted birth weight percentile (BWT%ile) and neonatal intensive care unit (NICU) admission. Relationships between primary outcome variables and GLY exposure were assessed using univariate and multivariate linear and logistic regression models. Results Urine GLY levels above the limit of detection (0.1 ng/mL) were found in 186 of 187 (99%) pregnant women. Further analyses were limited to 155 pregnant women with singleton live births. The mean age of participants was 29 years, and the majority were non-Hispanic white (70%) or non-Hispanic Black (21%). The mean (± SD) urine GLY level was 3.33 ± 1.67 ng/mL. Newborn BWT%iles were negatively related to GLY (adjusted slope ± SE = -0.032 + 0.014, p = 0.023). Infants born to women living outside of Indiana’s large central metropolitan area were more likely to have a lower BWT%ile associated with mother’s first trimester GLY levels (slope ± SE = -0.064 ± 0.024, p = 0.007). The adjusted odds ratio for NICU admission and maternal GLY levels was 1.16 (95% CI: 0.90, 1.67, p = 0.233). Conclusion GLY was found in 99% of pregnant women in this Midwestern cohort. Higher maternal GLY levels in the first trimester were associated with lower BWT%iles and higher NICU admission risk. The results warrant further investigation on the effects of GLY exposure in human pregnancies in larger population studies.
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- 2022
6. Impacts of a glyphosate-based herbicide on the gut microbiome of three earthworm species (Alma millsoni, Eudrilus eugeniae and Libyodrilus violaceus): A pilot study
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Mistura Adeleke, Folarin O. Owagboriaye, S.O. Owa, A. A. Aladesida, Taofeek T. Adegboyega, G. A. Dedeke, Michael Antoniou, and Robin Mesnage
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Glyphosate ,Health, Toxicology and Mutagenesis ,Zoology ,010501 environmental sciences ,Toxicology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Eudrilus eugeniae ,Soil contamination ,Abundance (ecology) ,RA1190-1270 ,Microbiome ,0105 earth and related environmental sciences ,biology ,Pseudomonas ,Earthworm ,Pantoea ,Agriculture ,biology.organism_classification ,16S rRNA sequencing ,chemistry ,Toxicology. Poisons ,Proteobacteria ,030217 neurology & neurosurgery ,Roundup - Abstract
While the impact of glyphosate-based herbicides (GBHs) on earthworms has been studied, little is known about their effects on the earthworm gut microbiome. This study investigated the impact of a GBH on the gut microbial communities of three earthworm species (Alma millsoni, Eudrilus eugeniae and Libyodrilus violaceus). Earthworm species accommodated in soil were sprayed with 115.49 mL/m² of Roundup® Alphee or water. Gut microbiome composition was analysed using 16S rRNA Bacterial Tag-Encoded FLX Amplicon Pyrosequencing (bTEFAP) at the 8th week post-herbicide application. A profound shift in bacterial populationswas observed in all exposed earthworms with Proteobacteria becoming the dominant phylum. Affected bacteria were mostly from the genus Enterobacter, Pantoea and Pseudomonas, which together represented approximately 80 % of the total abundance assigned at the genus level in exposed earthworms, while they were present at a minor abundance (∼1%) in unexposed earthworms. Although consistent results were observed between the three groups of worm species, it is not possible to generalize these outcomes due to a lack of biological replicates, which does not allow for inferential statistical analysis. Nevertheless, our study is the first to report the effects of a GBH on the earthworm gut microbiome and paves the way for future more comprehensive investigations.
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- 2021
7. Improved strategies to counter the COVID-19 pandemic: Lockdowns vs. primary and community healthcare
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Heather M. Wallace, Victor A. Tutelyan, Riccardo Polosa, José L. Domingo, Pantelis G. Bagos, Ronald N. Kostoff, Anastastia Barbouni, George Lazopoulos, Félix Carvalho, Dimitrios Kouvelas, Izotov Bn, Vassiliki Yiakoumaki, Konstantinos Poulas, Theodoros V. Giannouchos, Apostolos Vantarakis, Michalis Leotsinidis, Michael Aschner, Konstantinos Farsalinos, Aristides M. Tsatsakis, Grigorios T. Gerotziafas, Anca Oana Docea, Thomas Hartung, Michael Antoniou, and Dimitrios Kouretas
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medicine.medical_specialty ,Health, Toxicology and Mutagenesis ,Population ,COVID-19 pandemic ,Population health ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Article ,03 medical and health sciences ,0302 clinical medicine ,RA1190-1270 ,Development economics ,Pandemic ,Health care ,medicine ,education ,ComputingMethodologies_COMPUTERGRAPHICS ,Hospital preparedness ,0105 earth and related environmental sciences ,education.field_of_study ,business.industry ,Social distance ,Public health ,Primary care ,Dilemma ,Preparedness ,Horizontal lockdowns ,Toxicology. Poisons ,Business ,030217 neurology & neurosurgery - Abstract
Graphical abstract, Highlights • The COVID-19 pandemic has challenged the healthcare capacity of many countries. • Strict, horizontal lockdowns have adverse social, economic and health effects that have not been fully considered. • Primary and community care have multiple roles in COVID-19 pandemic mitigation. • Greece is a case example of a country which neglected primary and community care, and in November 2020 implemented a second horizontal lockdown. • Primary and community care, represents the only realistic strategy for successful COVID-19 pandemic mitigation in the long-term., COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non−COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation.
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- 2021
8. Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome
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Michael Antoniou and Robin Mesnage
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Glyphosate ,Health, Toxicology and Mutagenesis ,Population ,Toxicology ,Applied Microbiology and Biotechnology ,Genome ,Article ,chemistry.chemical_compound ,Shikimate ,lcsh:RA1190-1270 ,Aromatic amino acids ,Shikimate pathway ,Microbiome ,Pesticides ,education ,lcsh:Toxicology. Poisons ,education.field_of_study ,Gut microbiome ,biology ,biology.organism_classification ,Biochemistry ,chemistry ,Metagenomics ,Metagenome ,Proteobacteria - Abstract
The herbicide active ingredient glyphosate can affect the growth of microorganisms, which rely on the shikimate pathway for aromatic amino acid biosynthesis. However, it is uncertain whether glyphosate exposure could lead to perturbations in the population of human gut microbiota. We have addressed this knowledge gap by analysing publicly available datasets to provide new insights into possible effects of glyphosate on the human gut microbiome. Comparison of the abundance of the shikimate pathway in 734 paired metagenomes and metatranscriptomes indicated that most gut bacteria do not possess a complete shikimate pathway, and that this pathway is mostly transcriptionally inactive in the human gut microbiome. This suggests that gut bacteria are mostly aromatic amino acid auxotrophs and thus relatively resistant to a potential growth inhibition by glyphosate. As glyphosate blocking of the shikimate pathway is via inhibition of EPSPS, we classified E. coli EPSPS enzyme homologues as class I (sensitive to glyphosate) and class II (resistant to glyphosate). Among 44 subspecies reference genomes, accounting for 72% of the total assigned microbial abundance in 2144 human faecal metagenomes, 9 subspecies have class II EPSPS. The study of publicly available gut metagenomes also indicated that glyphosate might be degraded by some Proteobacteria in the human gut microbiome using the carbon–phosphorus lyase pathway. Overall, there is limited experimental evidence available for the effects of glyphosate on the human gut microbiome. Further investigations using more advanced molecular profiling techniques are needed to ascertain whether glyphosate and glyphosate-based herbicides can alter the function of the gut microbiome with consequent health implications., Graphical abstract Unlabelled Image, Highlights • It is debated whether glyphosate can perturb the human gut microbiota • Gut microbiome EPSPS enzymes are predicted to be sensitive to glyphosate • Shikimate pathway is mostly transcriptionally inactive in the human gut microbiome • Most gut microbiome bacteria do not possess a complete shikimate pathway • Investigations using more advanced techniques such as metabolomics are needed
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- 2020
9. Limitations in the evidential basis supporting health benefits from a decreased exposure to pesticides through organic food consumption
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Robin Mesnage, Ioannis Tsakiris, Michael Antoniou, and Aristides M. Tsatsakis
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0301 basic medicine ,Consumption (economics) ,Organic product ,business.industry ,Consumer demand ,Food consumption ,010501 environmental sciences ,Health benefits ,Pesticide ,Toxicology ,01 natural sciences ,Intervention studies ,03 medical and health sciences ,030104 developmental biology ,Environmental health ,Food products ,Medicine ,business ,0105 earth and related environmental sciences - Abstract
Consumer demand for organic food is mostly based on the belief that organic products are healthier because they are less contaminated with pesticides. We explain why health benefits from a decreased exposure to pesticides through organic food consumption remain unsubstantiated. There is sufficient evidence to conclude that nonorganic food products contain higher levels of synthetic pesticides. However, a link between the consumption of an organic diet with health benefits is confounded by a number of lifestyle and demographic covariates. We recommend dietary intervention studies be conducted such as randomized double-blind placebo-controlled investigations to determine if a group of individuals consuming an organic wholefood diet or an equivalent nonorganic diet present any differences in health status.
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- 2020
10. Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators
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Alexandra Sorvina, Michael Antoniou, Zahra Esmaeili, Marina Kochetkova, Sorvina, Alexandra, Antoniou, Michael, Esmaeili, Zahra, and Kochetkova, Marina
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ectopic expression ,Cancer Research ,Oncology ,cancer ,cartilage ,extra-cellular matrix (ECM) ,bone - Abstract
The extracellular matrix (ECM) is the complex three-dimensional network of fibrous proteins and proteoglycans that constitutes an essential part of every tissue to provide support for normal tissue homeostasis. Tissue specificity of the ECM in its topology and structure supports unique biochemical and mechanical properties of each organ. Cancers, like normal tissues, require the ECM to maintain multiple processes governing tumor development, progression and spread. A large body of experimental and clinical evidence has now accumulated to demonstrate essential roles of numerous ECM components in all cancer types. Latest findings also suggest that multiple tumor types express, and use to their advantage, atypical ECM components that are not found in the cancer tissue of origin. However, the understanding of cancer-specific expression patterns of these ECM proteins and their exact roles in selected tumor types is still sketchy. In this review, we summarize the latest data on the aberrant expression of bone and cartilage ECM proteins in epithelial cancers and their specific functions in the pathogenesis of carcinomas and discuss future directions in exploring the utility of this selective group of ECM components as future drug targets. Refereed/Peer-reviewed
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- 2023
11. Sustained transgene expression from sleeping beauty DNA transposons containing a core fragment of the HNRPA2B1-CBX3 ubiquitous chromatin opening element (UCOE)
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Michael Antoniou, Kristian Alsbjerg Skipper, Anne Kruse Hollensen, and Jacob Giehm Mikkelsen
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Transposable element ,Heterochromatin ,Transgene ,lcsh:Biotechnology ,CHO Cells ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cricetulus ,Cricetinae ,lcsh:TP248.13-248.65 ,Gene silencing ,Animals ,DNA transposon ,Transgenes ,Promoter Regions, Genetic ,030304 developmental biology ,0303 health sciences ,Promoter ,DNA Methylation ,Chromatin ,Cell biology ,chemistry ,030220 oncology & carcinogenesis ,DNA Transposable Elements ,DNA ,Biotechnology ,Research Article - Abstract
Background DNA transposon-based vectors are effective nonviral tools for gene therapy and genetic engineering of cells. However, promoter DNA methylation and a near-random integration profile, which can result in transgene integration into heterochromatin, renders such vectors vulnerable to transcriptional repression. Therefore, to secure persistent transgene expression it may be necessary to protect transposon-embedded transgenes with anti-transcriptional silencing elements. Results We compare four different protective strategies in CHO-K1 cells. Our findings show robust protection from silencing of transgene cassettes mediated by the ubiquitous chromatin-opening element (UCOE) derived from the HNRPA2B1-CBX3 locus. Using a bioinformatic approach, we define a shorter HNRPA2B1-CBX3 UCOE core fragment and demonstrate that this can robustly maintain transgene expression after extended passaging of CHO-K1 cells carrying DNA transposon vectors equipped with this protective feature. Conclusions Our findings contribute to the understanding of the mechanism of HNRPA2B1-CBX3 UCOE-based transgene protection and support the use of a correctly oriented core fragment of this UCOE for DNA transposon vector-based production of recombinant proteins in CHO-K1 cells.
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- 2019
12. Improving pesticide-use data for the EU
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Edward A. Straw, Dave Goulson, Michael Antoniou, Ellouise Leadbeater, Mark J. F. Brown, Elena Zioga, Charles Benbrook, Christopher J. Topping, Robin Mesnage, Ana López-Ballesteros, Johann G. Zaller, Marie-Pierre Chauzat, Dara A. Stanley, Blánaid White, Jane C. Stout, Peter J. Neumann, Robert Finger, Linzi J. Thompson, Niklas Möhring, Faculty of life Sciences and Medicine, Gene Expression and Therapy Group, Guy's Hospital [London]-King's College London School of Medicine, Benbrook Consulting Services, Laboratoire de Sophia Antipolis, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Department of Management, Technology, and Economics [ETH Zürich] (D-MTEC), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), University of Sussex, Royal Holloway [University of London] (RHUL), and Trinity College Dublin
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630 Agriculture ,Ecology ,[SDV]Life Sciences [q-bio] ,Agriculture ,010501 environmental sciences ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Pesticide use ,Environmental protection ,590 Animals (Zoology) ,Environmental science ,030212 general & internal medicine ,Pesticides ,ComputingMilieux_MISCELLANEOUS ,Ecology, Evolution, Behavior and Systematics ,Environmental Monitoring ,0105 earth and related environmental sciences - Abstract
International audience
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- 2021
13. Cytotoxicity mechanisms and composition of the glyphosate formulated herbicide RangerPro
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Scarlett Ferguson, Robin Mesnage, Francesca Mazzacuva, John Halket, Anna Caldwell, and Michael Antoniou
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medicine.disease_cause ,chemistry.chemical_compound ,Pulmonary surfactant ,chemistry ,Tallow ,Glyphosate ,Toxicity ,medicine ,media_common.cataloged_instance ,Amine gas treating ,Food science ,European union ,Cytotoxicity ,Oxidative stress ,media_common - Abstract
Understanding the nature of co-formulants and toxic effects of major glyphosate-based herbicide (GBH) formulations is considered a research priority. Indeed, the toxicity of the co-formulants present in GBHs have been widely discussed and the European Union recently banned the co-formulant polyoxyethylene tallow amine (POEA). We provide a foundation for the development of new environmental epidemiological studies by reporting the presence of the most commonly used POEA, known as POE-15 tallow amine, in the widely used US GBH RangerPro. In order to understand if POE-15 tallow amine is present in RangerPro at a concentration at which it can exert toxic effects, we also tested the cytotoxicity of this GBH compared to glyphosate and POE-15 tallow amine in the human epithelial cell line Caco-2, a representative of the human intestinal epithelium, and the first to be exposed from the human diet to glyphosate herbicides. The lethal concentration 50 for each of these substances was 125 μg/ml, 17200 μg/ml, and 5.7 μg/ml, for RangerPro, glyphosate and POE-15, respectively. The Caco-2 cell cytotoxicity assay indicated that RangerPro is more cytotoxic than glyphosate, suggesting that its toxicity can be due to the presence of the POE-15 surfactant. RangerPro and POE-15 tallow amine but not glyphosate exerted cell necrotic effects, but did not induce oxidative stress. We show that RangerPro contains POE-15 tallow amine at a concentration at which it could exert toxic effects, which offers a starting point for conducting surveys of co-formulant exposure in human populations.
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- 2021
14. Commentary: Novel strategies and new tools to curtail the health effects of pesticides
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Paul Winchester, Daniele Mandrioli, Robin Mesnage, Michael Antoniou, Charles Benbrook, Fiorella Belpoggi, Michelle Perro, Melissa J. Perry, and Philip J. Landrigan
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medicine.medical_specialty ,Sociology of scientific knowledge ,Health, Toxicology and Mutagenesis ,Decision Making ,Disease ,010501 environmental sciences ,Risk Assessment ,01 natural sciences ,Pesticide toxicity ,Toxicology studies ,03 medical and health sciences ,Testing protocols ,medicine ,Animals ,Humans ,Pesticides ,030304 developmental biology ,0105 earth and related environmental sciences ,0303 health sciences ,Scope (project management) ,Public health ,Public Health, Environmental and Occupational Health ,Environmental Exposure ,Industrial medicine. Industrial hygiene ,people.cause_of_death ,RC963-969 ,Risk analysis (engineering) ,Government Regulation ,Commentary ,Business ,Public aspects of medicine ,RA1-1270 ,people ,Risk assessment - Abstract
Background Flaws in the science supporting pesticide risk assessment and regulation stand in the way of progress in mitigating the human health impacts of pesticides. Critical problems include the scope of regulatory testing protocols, the near-total focus on pure active ingredients rather than formulated products, lack of publicly accessible information on co-formulants, excessive reliance on industry-supported studies coupled with reticence to incorporate published results in the risk assessment process, and failure to take advantage of new scientific opportunities and advances, e.g. biomonitoring and “omics” technologies. Recommended Actions Problems in pesticide risk assessment are identified and linked to study design, data, and methodological shortcomings. Steps and strategies are presented that have potential to deepen scientific knowledge of pesticide toxicity, exposures, and risks. We propose four solutions: (1) End near-sole reliance in regulatory decision-making on industry-supported studies by supporting and relying more heavily on independent science, especially for core toxicology studies. The cost of conducting core toxicology studies at labs not affiliated with or funded directly by pesticide registrants should be covered via fees paid by manufacturers to public agencies. (2) Regulators should place more weight on mechanistic data and low-dose studies within the range of contemporary exposures. (3) Regulators, public health agencies, and funders should increase the share of exposure-assessment resources that produce direct measures of concentrations in bodily fluids and tissues. Human biomonitoring is vital in order to quickly identify rising exposures among vulnerable populations including applicators, pregnant women, and children. (4) Scientific tools across disciplines can accelerate progress in risk assessments if integrated more effectively. New genetic and metabolomic markers of adverse health impacts and heritable epigenetic impacts are emerging and should be included more routinely in risk assessment to effectively prevent disease. Conclusions Preventing adverse public health outcomes triggered or made worse by exposure to pesticides will require changes in policy and risk assessment procedures, more science free of industry influence, and innovative strategies that blend traditional methods with new tools and mechanistic insights.
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- 2021
15. Alterations in small RNA profiles in liver following a subchronic exposure to a low-dose pesticide mixture in Sprague-Dawley rats
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Michael Antoniou, Robin Mesnage, Nadiya Mahmud, and Charles A. Mein
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Small RNA ,General Medicine ,Pesticide ,Biology ,Pharmacology ,Toxicology ,Rats ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,MicroRNAs ,chemistry ,Gene Expression Regulation ,Liver ,Imidacloprid ,Chlorpyrifos ,microRNA ,Biomarker (medicine) ,Animals ,Female ,Pesticides ,Transcriptome ,Gene ,Drug metabolism ,Phylogeny - Abstract
Small RNAs have emerged as a promising new type of biomarker to monitor health status and track the development of diseases. Here we report changes in the levels of small RNAs in the liver of rats exposed to a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole). Multivariate analysis with OPLS-DA methods showed that small RNA profiles can discriminate samples from pesticide treated rats from their concurrent controls. A total of 9 miRNAs were found to have their levels altered in the liver of the pesticide-treated rats in comparison to the controls, which included 7 that were downregulated (miR-22-5p, miR-193a-3p, miR-32-5p, miR-33-5p, miR-122-5p, miR-22-3p, miR-130a-3p) and 2 that were upregulated (miR-486-5p, miR-146a-5p). These miRNAs were predicted to regulate genes, which were found to have their expression altered by the pesticide mixture and have known health implications in the regulation of hepatic metabolism. This supports and extends our recent conclusions that high- throughput 'omics' analyses can reveal molecular perturbations, which can potentially act as sensitive and accurate markers of health risks arising from exposure to environmental pollutants such as pesticides.
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- 2021
16. Genotoxicity evaluation of 2,4-D, dicamba and glyphosate alone or in combination with cell reporter assays for DNA damage, oxidative stress and unfolded protein response
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Michael Antoniou, Robin Mesnage, Inger Brandsma, Gaonan Zhang, and Nynke Moelijker
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DNA damage ,Glycine ,Pharmacology ,Toxicology ,medicine.disease_cause ,chemistry.chemical_compound ,Mice ,Dicamba ,medicine ,Animals ,Humans ,Inducer ,Carcinogen ,Dose-Response Relationship, Drug ,Herbicides ,Mutagenicity Tests ,General Medicine ,Rats ,Oxidative Stress ,chemistry ,Glyphosate ,Unfolded protein response ,Unfolded Protein Response ,2,4-Dichlorophenoxyacetic Acid ,Genotoxicity ,Oxidative stress ,Food Science ,DNA Damage - Abstract
The current generation of carcinogenicity tests is often insufficient to predict cancer outcomes from pesticide exposures. In order to facilitate health risk assessment, The International Agency for Research on Cancer identified 10 key characteristics which are commonly exhibited by human carcinogens. The ToxTracker panel of six validated GFP-based mouse embryonic stem reporter cell lines is designed to measure a number of these carcinogenic properties namely DNA damage, oxidative stress and the unfolded protein response. Here we present an evaluation of the carcinogenic potential of the herbicides glyphosate, 2,4-D and dicamba either alone or in combination, using the ToxTracker assay system. The pesticide 2,4-D was found to be a strong inducer of oxidative stress and an unfolded protein response. Dicamba induced a mild oxidative stress response, whilst glyphosate did not elicit a positive outcome in any of the assays. The results from a mixture of the three herbicides was primarily an oxidative stress response, which was most likely due to 2,4-D with dicamba or glyphosate only playing a minor role. These findings provide initial information regarding the risk assessment of carcinogenic effects arising from exposure to a mixture of these herbicides.
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- 2021
17. Effects of single and combined toxic exposures on the gut microbiome: Current knowledge and future directions
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Anna Psaroulaki, Robin Mesnage, John Tsiaoussis, Aristidis Tsatsakis, Constantine I. Vardavas, Ioannis Koliarakis, Michael Antoniou, and Izotov Bn
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0301 basic medicine ,food.ingredient ,Computational biology ,Gut flora ,Toxicology ,Hazardous Substances ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,food ,Humans ,Pollutant ,biology ,Food additive ,General Medicine ,Pesticide ,biology.organism_classification ,Gut microbiome ,Gastrointestinal Microbiome ,030104 developmental biology ,chemistry ,Metagenomics ,Environmental Pollutants ,030217 neurology & neurosurgery ,Toxicant - Abstract
Human populations are chronically exposed to mixtures of toxic chemicals. Predicting the health effects of these mixtures require a large amount of information on the mode of action of their components. Xenobiotic metabolism by bacteria inhabiting the gastrointestinal tract has a major influence on human health. Our review aims to explore the literature for studies looking to characterize the different modes of action and outcomes of major chemical pollutants, and some components of cosmetics and food additives, on gut microbial communities in order to facilitate an estimation of their potential mixture effects. We identified good evidence that exposure to heavy metals, pesticides, nanoparticles, polycyclic aromatic hydrocarbons, dioxins, furans, polychlorinated biphenyls, and non-caloric artificial sweeteners affect the gut microbiome and which is associated with the development of metabolic, malignant, inflammatory, or immune diseases. Answering the question ‘Who is there?’ is not sufficient to define the mode of action of a toxicant in predictive modeling of mixture effects. Therefore, we recommend that new studies focus to simulate real-life exposure to diverse chemicals (toxicants, cosmetic/food additives), including as mixtures, and which combine metagenomics, metatranscriptomics and metabolomic analytical methods achieving in that way a comprehensive evaluation of effects on human health.
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- 2019
18. Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells
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Martina Biserni, Michael Antoniou, Robin Mesnage, Armel Nicolas, Cristina Vazquez Martin, and Francesco V. Rao
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Glycine-tRNA Ligase ,Models, Molecular ,0301 basic medicine ,Glyphosate ,Proteome ,Direct evidence ,Glycine ,Gene Expression ,lcsh:Medicine ,Proteomics ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Humans ,030212 general & internal medicine ,lcsh:Science (General) ,lcsh:QH301-705.5 ,Herbicides ,Chemistry ,lcsh:R ,General Medicine ,Neoplasm Proteins ,Research Note ,030104 developmental biology ,Biochemistry ,lcsh:Biology (General) ,Toxicity ,Cancer cell ,Protein folding ,Protein Processing, Post-Translational ,lcsh:Q1-390 - Abstract
Objectives Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome. Results Comparative statistical analysis of global proteome changes between glyphosate treated and non-treated samples did not show significant differences. Crucially, filtering of data to focus analysis on peptides potentially bearing glycine for glyphosate replacement revealed that the TMT reporter intensity pattern of all candidates showed conclusively that they are all false discoveries, with none displaying the expected TMT pattern for such a substitution. Thus, the assertion that glyphosate substitutes for glycine in protein polypeptide chains is incorrect. Electronic supplementary material The online version of this article (10.1186/s13104-019-4534-3) contains supplementary material, which is available to authorized users.
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- 2019
19. Quizalofop-p-Ethyl Induces Adipogenesis in 3T3-L1 Adipocytes
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Raquel Ferro, Charles A. Mein, Theodoros Xenakis, Robin Mesnage, Michael Antoniou, Eva Wozniak, and Martina Biserni
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Molecular, Biochemical, and Systems Toxicology ,0301 basic medicine ,medicine.medical_specialty ,Estrogen receptor ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,obesogen ,glyphosate ,3T3-L1 Cells ,Quinoxalines ,Internal medicine ,Adipocytes ,medicine ,Animals ,Receptor ,pesticide ,3T3-L1 ,0105 earth and related environmental sciences ,Adipogenesis ,Antiglucocorticoid ,Lipid metabolism ,Lipid Metabolism ,quizalofop ,PPAR gamma ,030104 developmental biology ,Endocrinology ,chemistry ,Nuclear receptor ,Propionates ,Obesogen - Abstract
Exposure to endocrine disrupting chemicals is an established risk factor for obesity. The most commonly used pesticide active ingredients have never been tested in an adipogenesis assay. We tested for the first time the potential of glyphosate, 2, 4-dichlorophenoxyacetic acid, dicamba, mesotrione, isoxaflutole, and quizalofop-p-ethyl (QpE) to induce lipid accumulation in murine 3T3-L1 adipocytes. Only QpE caused a dose-dependent statistically significant triglyceride accumulation from a concentration of 5 up to 100 µM. The QpE commercial formulation Targa Super was 100 times more cytotoxic than QpE alone. Neither the estrogen receptor antagonist ICI 182, 780 nor the glucocorticoid receptor antagonist RU486 was able to block the QpE-induced lipid accumulation. RNAseq analysis of 3T3-L1 adipocytes exposed to QpE suggests that this compound exerts its lipid accumulation effects via a peroxisome proliferator-activated receptor gamma (PPARγ)-mediated pathway, a nuclear receptor whose modulation influences lipid metabolism. QpE was further shown to be active in a PPARγ reporter gene assay at 100 µM, reaching 4% of the maximal response produced by rosiglitazone, which acts as a positive control. This indicates that lipid accumulation induced by QpE is only in part caused by PPARγ activation. The lipid accumulation capability of QpE we observe suggest that this pesticide, whose use is likely to increase in coming years may have a hitherto unsuspected obesogenic property.
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- 2019
20. Comparative toxicogenomics of glyphosate and Roundup herbicides by mammalian stem cell-based genotoxicity assays and molecular profiling in Sprague-Dawley rats
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Mariam Ibragim, Laura Falcioni, Robin Mesnage, Michael Antoniou, Charles A. Mein, Daniele Mandrioli, Eva Tibaldi, Fiorella Belpoggi, Inger Brandsma, Emanuel Savage, and Emma Bourne
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DNA damage ,Glycine ,toxicogenomic ,Biology ,Pharmacology ,Toxicology ,medicine.disease_cause ,Toxicogenetics ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,glyphosate ,medicine ,oxidative stress ,Animals ,Carcinogen ,Mammals ,DNA methylation ,Herbicides ,Stem Cells ,genotoxicity ,Molecular biology ,In vitro ,Rats ,MicroRNAs ,chemistry ,Glyphosate ,Female ,Toxicogenomics ,Carcinogenesis ,Genotoxicity ,Oxidative stress ,DNA Damage - Abstract
Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remains controversial. As GBHs are more cytotoxic that glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs namely MON 52276 (EU), MON 76473 (UK) and MON 76207 (USA) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (both at 0.5, 50, 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased mir-30 while miR-10 levels were increased. DNA methylation profiling of liver revealed 5,727 and 4,496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate.
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- 2021
21. Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats
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Mariam Ibragim, Romy D. Zwittink, Quinten R Ducarmon, Michael Antoniou, Laura Falcioni, Maxime Teixeira, Caroline Amiel, Jean-Michel Panoff, Robin Mesnage, Daniele Mandrioli, Emma Bourne, Fiorella Belpoggi, Charles A. Mein, and Emanuel Savage
- Subjects
0301 basic medicine ,QH301-705.5 ,Medicine (miscellaneous) ,010501 environmental sciences ,Biology ,Pharmacology ,medicine.disease_cause ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Article ,Transcriptome ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Metabolomics ,medicine ,Animals ,Biology (General) ,Pesticides ,0105 earth and related environmental sciences ,Nicotinamide ,Dose-Response Relationship, Drug ,Pesticide ,Rats ,Gastrointestinal Tract ,030104 developmental biology ,Phenotype ,chemistry ,Risk factors ,Liver ,Chlorpyrifos ,Toxicity ,Female ,General Agricultural and Biological Sciences ,Oxidative stress ,Hormone - Abstract
Health effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect. Contrastingly, serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested activation of an oxidative stress response. This was not reflected by gut microbial community composition changes evaluated by shotgun metagenomics. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included the regulation of response to steroid hormones and the activation of stress response pathways. Genome-wide DNA methylation analysis of the same liver samples showed that 4,255 CpG sites were differentially methylated. Overall, we demonstrated that in-depth molecular profiling in laboratory animals exposed to low concentrations of pesticides allows the detection of metabolic perturbations that would remain undetected by standard regulatory biochemical measures and which could thus improve the predictability of health risks from exposure to chemical pollutants., Using a multi-omics platform, Mesnage et al present an extensive dataset that reports the effects of low-dose pesticides frequently detected in food on Sprague-Dawley rats. This study suggests potential metabolic biomarkers that may predict health risks from exposure to chemical pollutants.
- Published
- 2021
22. Analytical strategies to study the gut microbiome in toxicology
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Robin Mesnage and Michael Antoniou
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Herbicide glyphosate ,Context (language use) ,Microbiome ,Computational biology ,Health risk ,Biology ,Gut microbiome - Abstract
Bacteria in the gut have the ability to affect the toxicity of chemicals. The development of laboratory-based models to study the toxicity of chemicals on the gut microbiome in the context of regulatory health risk assessments is still in its infancy. We provide an overview of the different DNA sequencing strategies to study the gut microbiome, illustrated by results of studies investigating the effects of the herbicide glyphosate. This provides a list of actionable points that may help the scientific community improve the quality of gut microbiome animal toxicity studies. More studies are needed to improve the standardization of generating, storing, and analyzing microbiome data, but also to unravel knowledge gaps such as the need for the definition of a healthy microbiome, as well as the need for research on host–microbiome interactions and its pathological aspects.
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- 2021
23. Contributors
- Author
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Michael Antoniou, Charles M. Benbrook, Rachel Benbrook, Carsten A. Brühl, Mirco Bundschuh, Nicolas de Sadeleer, Sylvain Dulaurent, Souleiman El Balkhi, Robin Mesnage, John Peterson Myers, Sophie Oster, Franck Saint-Marcoux, András Székács, Laura N. Vandenberg, and Johann G. Zaller
- Published
- 2021
24. Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats
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Quinten R Ducarmon, Daniele Mandrioli, Romy D. Zwittink, Jean Michel Panoff, Laura Falcioni, Maxime Teixeira, Anna Caldwell, Robin Mesnage, Francesca Mazzacuva, Fiorella Belpoggi, Caroline Amiel, John M. Halket, and Michael Antoniou
- Subjects
animal structures ,Health, Toxicology and Mutagenesis ,Glycine ,010501 environmental sciences ,Gut flora ,01 natural sciences ,Microbiology ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,Sprague dawley rats ,Metabolome ,Animals ,Shikimate pathway ,030212 general & internal medicine ,Health implications ,0105 earth and related environmental sciences ,Acinetobacter ,integumentary system ,biology ,Herbicides ,Research ,fungi ,Public Health, Environmental and Occupational Health ,food and beverages ,biology.organism_classification ,Gastrointestinal Microbiome ,Rats ,Blood ,chemistry ,Glyphosate ,Metagenomics ,Shotgun metagenomics - Abstract
BACKGROUND: There is intense debate on whether glyphosate can inhibit the shikimate pathway of gastrointestinal microorganisms, with potential health implications.OBJECTIVES: We tested whether glyphosate or its representative EU herbicide formulation Roundup MON 52276 affects the rat gut microbiome.METHODS: We combined cecal microbiome shotgun metagenomics with serum and cecum metabolomics to assess the effects of glyphosate [0.5, 50, 175 mg=kg body weight oBW thorn per day] or MON 52276 at the same glyphosate-equivalent doses, in a 90-d toxicity test in rats.RESULTS: Glyphosate and MON 52276 treatment resulted in ceca accumulation of shikimic acid and 3-dehydroshikimic acid, suggesting inhibition of 5-enolpyruvylshikimate-3-phosphate synthase of the shikimate pathway in the gut microbiome. Cysteinylglycine, c-glutamylglutamine, and valylglycine levels were elevated in the cecal microbiome following glyphosate and MON 52276 treatments. Altered cecum metabolites were not differentially expressed in serum, suggesting that the glyphosate and MON 52276 impact on gut microbial metabolism had limited consequences on physiological biochemistry. Serum metabolites differentially expressed with glyphosate treatment were associated with nicotinamide, branched-chain amino acid, methionine, cysteine, and taurine metabolism, indicative of a response to oxidative stress. MON 52276 had similar, but more pronounced, effects than glyphosate on the serum metabolome. Shotgun metagenomics of the cecum showed that treatment with glyphosate and MON 52276 resulted in higher levels of Eggerthella spp., Shinella zoogleoides, Acinetobacter johnsonii, and Akkermansia muciniphila. Shinella zoogleoides was higher only with MON 52276 exposure. In vitro culture assays with Lacticaseibacillus rhamnosus strains showed that Roundup GT plus inhibited growth at concentrations at which MON 52276 and glyphosate had no effect.DISCUSSION: Our study highlights the power of multi-omics approaches to investigate the toxic effects of pesticides. Multi-omics revealed that glyphosate and MON 52276 inhibited the shikimate pathway in the rat gut microbiome. Our findings could be used to develop biomarkers for epidemiologi cal studies aimed at evaluating the effects of glyphosate herbicides on humans. https://doi.org/10.1289/EHP6990
- Published
- 2021
25. List of contributors
- Author
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Giorgia Adani, Evgenios Agathokleous, Athina-Maria Aloizou, Arturo Anadon, Michael Antoniou, Irma Ares, Michael Aschner, Katerina Aslanoglou, Daiana Silva Avila, Nausicaa Berselli, J. Biosca-Brull, Dimitrios P. Bogdanos, Michael B. Briggs, Edward J. Calabrese, Daniela Calina, Joao Paulo Capela, Helena Carmo, Felix Carvalho, N. Chandrasekaran, M.T. Colomina, Carolina Constantin, Emanuela Corsini, Chiara Costa, Vera Marisa Costa, Efthimios Dardiotis, Carlos Augusto Fernandes de Oliveira, Flavia Suelen de Oliveira Pereira, Pasquale Del Gaudio, Tianqi Deng, Ana Rita Dias Carvalho, Aleksandra Buha Djordjevic, Anca Oana Docea, Nikolaos Drakoulis, Konstantinos Farsalinos, Concettina Fenga, Tommaso Filippini, Andreas D. Flouris, Persefoni Fragkiadaki, Domniki Fragou, Larissa Tuanny Franco, Jingqi Fu, Valentina Galbiati, Carlos A. Garcia-Gonzalez, Spyridoula Georgaki, Briguglio Giusi, Giorgos Gkikas, Kirill Golokhvast, Telma M. Gomes, Marina Goumenou, L. Guardia-Escote, Jiabin Guo, Thomas Hartung, Antonio F. Hernandez, Ekhtear Hossain, Leonidas G. Ioannou, Helena Kandarova, Spyros P. Karakitsios, Vasiliki Karzi, George E. Kochiadakis, Ronald N. Kostoff, Leda Kovatsi, Christopher L. Kuhlman, Christina Kyriakos, Ioanna Lagou, Lawrence H. Lash, Ioannis Liampas, John C. Lipscomb, Shengnan Liu, Ambra Maddalon, Rui F. Malheiro, Konstantinos Mantzios, Denisa Margina, Maria-Aranzazu Martinez, Marta Martinez, Maria-Rosa Martinez-Larranaga, Robin Mesnage, Panayiotis D. Mitsias, M. Morales, Khurram Muaz, Amitava Mukherjee, Monica Neagu, Katerina Nikitara, Dragana Nikitovic, Taxiarchis Konstantinos Nikolouzakis, George Mihai Nitulescu, Georgiana Nitulescu, Octavian Tudorel Olaru, Akinobu Ota, Eren Ozcagli, Maria Papasavva, Georgia Pateraki, C. Perez-Fernandez, Jingbo Pi, Konstantin Pikula, Alan L. Porter, Carmen Purdel, Weidong Qu, Thiagarajan Raman, Elisavet Renieri, Ramin Rezaee, F. Sanchez-Santed, Evangelia Sarandi, Dimosthenis A. Sarigiannis, Kasturi Sarkar, R. Seenivasan, Parames C. Sil, Joao P. Silva, Vasileios Siokas, Marcell Valandro Soares, Paul M. Stemmer, Vignesh Thiagarajan, Konstantinos Tsarouhas, Aristidis M. Tsatsakis, Ioannis Tsatsakis, Christina Tsitsimpikou, Dimitris Tsoukalas, Lydia Tsoutsoubi, Anca Ungurianu, Elena Vakonaki, Alexander Vardavas, Constantine Vardavas, Loukia Vassilopoulou, Aristidis S. Veskoukis, Marco Vinceti, Marc Vives Enrich, Zacharenia Vlata, Md Wahiduzzaman, Heather M. Wallace, Huihui Wang, Yuanyuan Xu, and Qiang Zhang
- Published
- 2021
26. Mammalian toxicity of herbicides used in intensive GM crop farming
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Michael Antoniou and Robin Mesnage
- Subjects
business.industry ,Alachlor ,Biology ,Biotechnology ,Mesotrione ,chemistry.chemical_compound ,Glufosinate ,chemistry ,Glyphosate ,Dicamba ,Atrazine ,Acetochlor ,business ,Metolachlor - Abstract
The toxicity of major herbicides on mammalian physiology is reviewed, with a focus on herbicides associated with agricultural systems employing genetically modified crops: glyphosate, 2,4-D, dicamba, glufosinate, quizalofop, sulfonylurea, imidazolinones, mesotrione, and isoxaflutole. Other products used in intensive agriculture worldwide are discussed: paraquat, atrazine, metolachlor, acetochlor, and alachlor. The frequent withdrawal of toxic ingredients creates the impression that herbicides are increasingly safe, but also implies that their initial assessment was insufficient. We highlight knowledge and technical gaps in the determination of safety thresholds: long-term effects of herbicides and their combinations at environmental levels (i.e., real-life exposure scenarios), epigenetics effects, and impacts on the gut microbiome are insufficiently tested. Most of the studies are focused on a few usual suspects (glyphosate, 2,4-D, atrazine), and the toxicology of some major herbicides remains underexplored. This amplifies the inescapable gap between the introduction of a new herbicide and the detection of its health effects.
- Published
- 2021
27. Multi-omics phenotyping of the gut-liver axis allows health risk predictability from in vivo subchronic toxicity tests of a low-dose pesticide mixture
- Author
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Emanuel Savage, Charles A. Mein, Fiorella Belpoggi, Quinten R Ducarmon, Caroline Amiel, Michael Antoniou, Emma Bourne, Jean-Michel Panoff, Daniele Mandrioli, Romy D. Zwittink, Maxime Teixeira, Laura Falcioni, and Robin Mesnage
- Subjects
Transcriptome ,chemistry.chemical_compound ,Acceptable daily intake ,chemistry ,Nicotinamide ,Lactobacillus rhamnosus ,biology ,Pesticide residue ,In vivo ,Chlorpyrifos ,Pesticide ,Pharmacology ,biology.organism_classification - Abstract
Human health effects from chronic exposure to mixtures of pesticide residues are little investigated. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in an in vivo subchronic toxicity test of a mixture of six pesticide active ingredients frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole). Sprague-Dawley rats were administered with the pesticide mixture with each ingredient at its regulatory permitted acceptable daily intake. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little or no physiological effects from exposure to the pesticide mixture. In marked contrast, analysis of the host-gut microbiome axis using serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested the initiation of a cell danger response, including adaptation to oxidative stress. Only limited effects were detected on the caecum microbiota by shotgun metagenomics. Further analyses of in vitro bacterial cultures showed that growth of Lactobacillus rhamnosus and Escherichia coli strains was negatively impacted by the pesticide mixture at concentrations that were not inhibitory when exposure was to a single agent. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included those involved in the regulation of response to hormones and correlated with previously reported transcriptome changes following administration of nicotinamide. Genome-wide DNA methylation analysis of the same liver samples showed that 4255 CpG sites were differentially methylated (> 10% difference). Overall, we demonstrated that unlike standard blood biochemical and organ histological analysis, in-depth molecular profiling using a combination of high-throughput ‘-omics’ methods in laboratory animals exposed to low concentrations of pesticides reveals metabolic effects on the gut-liver axis, which can potentially be used as biomarkers for the prediction of future negative health outcomes. Our data suggest that adoption of multi-omics as part of regulatory risk assessment procedures will result in more accurate outcome measures, with positive public health implications.
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- 2020
28. Gut microbiome metagenomics to understand how xenobiotics impact human health
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Aristidis Tsatsakis, Michael Antoniou, Robin Mesnage, Dimitrios Tsoukalas, and George N. Goulielmos
- Subjects
0301 basic medicine ,Computational biology ,Disease ,Biology ,Toxicology ,Gut microbiome ,03 medical and health sciences ,Human health ,chemistry.chemical_compound ,030104 developmental biology ,Transgenerational epigenetics ,chemistry ,Metagenomics ,Microbiome ,Xenobiotic ,Drug metabolism - Abstract
Xenobiotic metabolism by bacteria inhabiting the gastrointestinal tract has a major influence on health. The large genetic and enzymatic repertoire carried out by gut microbial communities provides them with the ability to affect the therapeutic efficacy, toxicity and pharmacokinetic parameters of many chemicals. The gut microbiome is a promising source of drug targets and noninvasive biomarkers, for the early detection of diseases and personalised medicine against cancer. A large number of animal species, including humans, have evolved to feed on toxic or indigestible plants by carrying xenobiotic-degrading microbial communities. Vertical transmission of gut microbiome metabolic capabilities to future generations could even be a mode of transgenerational inheritance. Changes in human gut microbiome composition have been implicated in a wide range of clinical conditions, some of which develop locally in the intestine, such as Crohn's disease, but many others occurring at distant sites, such as metabolic diseases. Recent advances in next-generation sequencing have opened new avenues to determine the role of microbiomes in the toxicity of chemicals, expanding the field of genomic toxicology to a broader metagenomic toxicology research area. In this review, we present key gut microbiome research areas, with a focus on metabolism of xenobiotics by the gut microbiome.
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- 2018
29. Shotgun metagenomics and metabolomics reveal glyphosate alters the gut microbiome of Sprague-Dawley rats by inhibiting the shikimate pathway
- Author
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Jean-Michel Panoff, Michael Antoniou, Caroline Amiel, Romy D. Zwittink, Maxime Teixeira, Robin Mesnage, Daniele Mandrioli, Fiorella Belpoggi, Quinten R Ducarmon, and Laura Falcioni
- Subjects
Caecum ,chemistry.chemical_compound ,Gastrointestinal tract ,Metabolomics ,chemistry ,Glyphosate ,Aromatic amino acids ,Shikimate pathway ,Microbiome ,Biology ,Shikimic acid ,biology.organism_classification ,Microbiology - Abstract
There is intense debate as to whether glyphosate can interfere with aromatic amino acid biosynthesis in microorganisms inhabiting the gastrointestinal tract, which could potentially lead to negative health outcomes. We have addressed this major gap in glyphosate toxicology by using a multi-omics strategy combining shotgun metagenomics and metabolomics. We tested whether glyphosate (0.5, 50, 175 mg/kg bw/day), or its representative EU commercial herbicide formulation MON 52276 at the same glyphosate equivalent doses, has an effect on the rat gut microbiome in a 90-day subchronic toxicity test. Clinical biochemistry measurements in blood and histopathological evaluations showed that MON 52276 but not glyphosate was associated with statistically significant increase in hepatic steatosis and necrosis. Similar lesions were also present in the liver of glyphosate-treated groups but not in the control group. Caecum metabolomics revealed that glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase in the shikimate pathway as evidenced by an accumulation of shikimic acid and 3-dehydroshikimic acid. Levels of caecal microbiome dipeptides involved in the regulation of redox balance (γ-glutamylglutamine, cysteinylglycine, valylglycine) had their levels significantly increased. Shotgun metagenomics showed that glyphosate affected caecum microbial community structure and increased levels of Eggerthella spp. and Homeothermacea spp.. MON 52276, but not glyphosate, increased the relative abundance of Shinella zoogleoides. Since Shinella spp. are known to degrade alkaloids, its increased abundance may explain the decrease in solanidine levels measured with MON 52776 but not glyphosate. Other glyphosate formulations may have different effects since Roundup® GT Plus inhibited bacterial growth in vitro at concentrations at which MON 52276 did not present any visible effect. Our study highlights the power of a multiomics approach to investigate effects of pesticides on the gut microbiome. This revealed the first biomarker of glyphosate effects on rat gut microbiome. Although more studies will be needed to ascertain if there are health implications arising from glyphosate inhibition of the shikimate pathway in the gut microbiome, our findings can be used in environmental epidemiological studies to understand if glyphosate can have biological effects in human populations.Graphical Abstract
- Published
- 2019
30. Comparison of transcriptome responses to glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line
- Author
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Martina Biserni, Robin Mesnage, Charles A. Mein, Theodoros Xenakis, Michael Antoniou, and Eva Wozniak
- Subjects
0301 basic medicine ,Glyphosate ,Health, Toxicology and Mutagenesis ,Genetically modified crops ,010501 environmental sciences ,Fatty acid degradation ,Toxicology ,01 natural sciences ,Article ,Mesotrione ,Transcriptome ,03 medical and health sciences ,chemistry.chemical_compound ,lcsh:RA1190-1270 ,NAFLD ,Metabolome ,0105 earth and related environmental sciences ,lcsh:Toxicology. Poisons ,Quizalofop ,chemistry.chemical_classification ,Chemistry ,030104 developmental biology ,Biochemistry ,Toxicity ,RNA-seq ,HepaRG ,Isoxaflutole ,Polyunsaturated fatty acid - Abstract
Highlights • We evaluated glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione. • Gene expression alterations were measured in the HepaRG liver cell line. • Quizalofop-p-ethyl was the most toxic, causing alterations in lipid metabolism. • Isoxaflutole was less toxic, but was revealed as a possible PXR activator. • Glyphosate and mesotrione only caused subtle changes in transcriptome profiles., Use and thus exposure to quizalofop-p-ethyl, isoxaflutole, mesotrione and glyphosate, which are declared as active principles in commercial formulations of herbicides, is predicted to rapidly increase in coming years in an effort to overcome the wide-spread appearance of glyphosate-resistant weeds, especially in fields where glyphosate-tolerant genetically modified crops are cultivated in the USA. Thus, there is an urgent need for an evaluation of metabolic effects of new pesticide ingredients used to replace glyphosate. As the liver is a primary target of chemical pollutant toxicity, we have used the HepaRG human liver cell line as a model system to assess the toxicological insult from quizalofop-p-ethyl, isoxaflutole, mesotrione and glyphosate by determining alterations in the transcriptome caused by exposure to three concentrations of each of these compounds, including a low environmentally relevant dose. RNA-seq data were analysed with HISAT2, StringTie and Ballgown. Quizalofop-p-ethyl was found to be the most toxic of the pesticide ingredients tested, causing alterations in gene expression that are associated with pathways involved in fatty acid degradation and response to alcoholism. Isoxaflutole was less toxic, but caused detectable changes in retinol metabolism and in the PPAR signalling pathway at a concentration of 1 mM. ToxCast data analysis revealed that isoxaflutole activated PPAR gamma receptor and pregnane X responsive elements in reporter gene assays. Glyphosate and mesotrione caused subtle changes in transcriptome profiles, with too few genes altered in their function to allow a reliable pathway analysis. In order to explore the effects of glyphosate in greater depth and detail, we undertook a global metabolome profiling. This revealed a decrease in free long chain fatty acids and polyunsaturated fatty acid levels at the lowest concentration (0.06 μM) of glyphosate, although no effects were detected at the two higher concentrations tested, perhaps suggesting a non-linear dose response. This surprising result will need to be confirmed by additional studies. Overall, our findings contribute to filling the knowledge gap regarding metabolic toxicity that can potentially arise from exposure to these four herbicide active principles.
- Published
- 2018
31. The Scope for Thalassemia Gene Therapy by Disruption of Aberrant Regulatory Elements
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Soteroula Christou, Michael Antoniou, Carsten W. Lederer, Argyro Floga, Petros Patsali, Petros Ladas, Marina Kleanthous, Toni Cathomen, Claudio Mussolino, Maria Sitarou, and Annita Kolnagou
- Subjects
thalassemia ,Genetic enhancement ,In silico ,Article ,03 medical and health sciences ,0302 clinical medicine ,Genome editing ,Cpf1 ,TALEN ,Transcription (biology) ,Medicine ,CRISPR ,Indel ,CRISPR/Cas9 ,030304 developmental biology ,Genetics ,0303 health sciences ,Transcription activator-like effector nuclease ,Cas12a ,business.industry ,Effector ,gene editing ,General Medicine ,gene therapy ,3. Good health ,ATMP ,advanced therapy medicinal product ,business ,030217 neurology & neurosurgery - Abstract
The common IVSI-110 (G>, A) &beta, thalassemia mutation is a paradigm for intronic disease-causing mutations and their functional repair by non-homologous end joining-mediated disruption. Such mutation-specific repair by disruption of aberrant regulatory elements (DARE) is highly efficient, but to date, no systematic analysis has been performed to evaluate disease-causing mutations as therapeutic targets. Here, DARE was performed in highly characterized erythroid IVSI-110(G>, A) transgenic cells and the disruption events were compared with published observations in primary CD34+ cells. DARE achieved the functional correction of &beta, globin expression equally through the removal of causative mutations and through the removal of context sequences, with disruption events and the restriction of indel events close to the cut site closely resembling those seen in primary cells. Correlation of DNA-, RNA-, and protein-level findings then allowed the extrapolation of findings to other mutations by in silico analyses for potential repair based on the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9, Cas12a, and transcription activator-like effector nuclease (TALEN) platforms. The high efficiency of DARE and unexpected freedom of target design render the approach potentially suitable for 14 known thalassemia mutations besides IVSI-110(G>, A) and put it forward for several prominent mutations causing other inherited diseases. The application of DARE, therefore, has a wide scope for sustainable personalized advanced therapy medicinal product development for thalassemia and beyond.
- Published
- 2019
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32. Evaluation of neonicotinoid insecticides for oestrogenic, thyroidogenic and adipogenic activity reveals imidacloprid causes lipid accumulation
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Michael Antoniou, Dilyana Genkova, Ludovic Wesolowski, Robin Mesnage, and Martina Biserni
- Subjects
0301 basic medicine ,Pregnane X receptor ,Thyroid hormone receptor ,Neonicotinoid ,Clothianidin ,010501 environmental sciences ,Pharmacology ,Biology ,Toxicology ,Thiacloprid ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Imidacloprid ,Thiamethoxam ,0105 earth and related environmental sciences ,Nitenpyram - Abstract
Few studies have investigated non-target effects of neonicotinoid insecticides on mammalian physiology. This is largely due to the widespread perception that their weak affinity for nicotinic acetylcholine receptor subtypes in vertebrates makes mammalian exposures unlikely to pose health risks. To the best of our knowledge, we describe the first investigation evaluating the interaction of seven principal neonicotinoid insecticides (thiamethoxam, imidacloprid, clothianidin, flupyradifurone, dinotefuran, nitenpyram, thiacloprid) with oestrogen and thyroid hormone receptors, as well as their adipogenic effects, in mammalian cell culture assay systems. An E-Screen with MCF-7 and T-Screen with GH3 cells respectively showed a lack of oestrogen and thyroid hormone receptor agonist effects for any of the neonicotinoids tested. Adipogenicity was assessed by the ability to stimulate lipid accumulation in adipocyte differentiated 3T3-L1 cells, with only imidacloprid scoring positive in this assay causing triglyceride accumulation from a concentration of 50 mg l-1 . Data mining of ToxCast high-throughput screening assays revealed that this adipogenic effect of imidacloprid is probably mediated via the pregnane X receptor.
- Published
- 2018
33. Short-hairpin RNA against aberrant HBBIVSI-110(G>A) mRNA restores β-globin levels in a novel cell model and acts as mono- and combination therapy for β-thalassemia in primary hematopoietic stem cells
- Author
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Petros Patsali, Soteroulla Christou, Marina Kleanthous, Maria Sitarou, Coralea Stephanou, Panayiota Papasavva, Michael Antoniou, and Carsten W. Lederer
- Subjects
0301 basic medicine ,Combination therapy ,Thalassemia ,beta-Globins ,Biology ,Cell Line ,Small hairpin RNA ,Mice ,03 medical and health sciences ,Text mining ,medicine ,Animals ,Humans ,RNA, Messenger ,Globin ,RNA, Small Interfering ,Online Only Articles ,Alleles ,Messenger RNA ,business.industry ,beta-Thalassemia ,Hematology ,Hematopoietic Stem Cells ,medicine.disease ,Combined Modality Therapy ,Molecular biology ,Haematopoiesis ,030104 developmental biology ,Gene Expression Regulation ,Mutation ,RNA Interference ,Stem cell ,business - Published
- 2018
34. Urinary excretion of herbicide co-formulants after oral exposure to roundup MON 52276 in rats
- Author
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Francesca Mazzacuva, Anna Caldwell, Michael Antoniou, Robin Mesnage, and John M. Halket
- Subjects
Acceptable daily intake ,Urine ,Absorption (skin) ,010501 environmental sciences ,01 natural sciences ,Biochemistry ,Rats, Sprague-Dawley ,Surface-Active Agents ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Biomonitoring ,Animals ,media_common.cataloged_instance ,030212 general & internal medicine ,European union ,0105 earth and related environmental sciences ,General Environmental Science ,media_common ,Detection limit ,Chromatography ,Herbicides ,Chemistry ,Rats ,Glyphosate ,Toxicity - Abstract
The toxicity of surfactants, which are an integral component of glyphosate-formulated products is an underexplored and highly debated subject. Since biomonitoring human exposure to glyphosate co-formulants is considered as a public health priority, we developed and validated a high-resolution mass spectrometry method to measure the urinary excretion of surfactants present in Roundup MON 52276, the European Union (EU) representative formulation of glyphosate-based herbicides. Quantification was performed measuring the 5 most abundant compounds in the mixture. We validated the method and showed that it is highly accurate, precise and reproducible with a limit of detection of 0.0004 μg/mL. We used this method to estimate the oral absorption of MON 52276 surfactants in Sprague-Dawley rats exposed to three concentrations of MON 52276 via drinking water for 90 days. MON 52276 surfactants were readily detected in urine of rats administered with this commercial Roundup formulation starting from a low concentration corresponding to the EU glyphosate acceptable daily intake. Our results provide a first step towards the implementation of surfactant co-formulant biomonitoring in human populations.
- Published
- 2021
35. Ubiquitous Chromatin-opening Elements (UCOEs): Applications in biomanufacturing and gene therapy
- Author
-
Jonathan J Neville, Joe Orlando, Michael Antoniou, Kimberly Mann, and Bethany McCloskey
- Subjects
0301 basic medicine ,Heterochromatin ,Transgene ,Genetic Vectors ,Bioengineering ,Computational biology ,Biology ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,Gene therapy ,Stable gene expression ,UCOE ,Humans ,Gene silencing ,Biomanufacturing ,Gene Silencing ,Transgenes ,Promoter Regions, Genetic ,Genetics ,Regulation of gene expression ,Ubiquitous chromatin opening element ,Genetic Therapy ,DNA Methylation ,Chromatin ,Housekeeping gene ,030104 developmental biology ,Gene Expression Regulation ,DNA methylation ,CpG Islands ,Biotechnology - Abstract
Ubiquitous Chromatin-opening Elements (UCOEs) are defined by their ability to consistently confer stable, site of integration-independent transgene expression that is proportional to copy number, including from within regions of heterochromatin such as centromeres. UCOEs structurally consist of methylation-free CpG islands encompassing single or dual divergently-transcribed housekeeping gene promoters. Since their discovery in 1999, UCOEs and their sub-fragments have found applications in areas of biotechnology requiring stable, reproducible, and high levels of gene expression. This review recounts the discovery of UCOEs and examines their current and future applications in protein therapeutic biomanufacturing and gene therapy.
- Published
- 2017
36. Editor’s Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells
- Author
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Matthew Arno, J. Christopher Corton, Sucharitha Balu, Robin Mesnage, Michael Antoniou, and Alexia Phedonos
- Subjects
0301 basic medicine ,Bisphenol A ,endocrine system ,endocrine ,Bisphenol ,medicine.drug_class ,Estrogen receptor ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Bisphenol AF ,03 medical and health sciences ,chemistry.chemical_compound ,bisphenol ,medicine ,0105 earth and related environmental sciences ,cell culture ,Chemistry ,urogenital system ,Bisphenol a Alternatives Activate Estrogen Receptors ,030104 developmental biology ,Bisphenol S ,Estrogen ,toxicogenomics ,Cancer cell ,Cancer research ,Estrogen receptor alpha ,hormones, hormone substitutes, and hormone antagonists ,estrogens - Abstract
Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in "BPA-free" products. We have compared estrogenic activity of BPA with 6 bisphenol analogues [bisphenol S (BPS); bisphenol F (BPF); bisphenol AP (BPAP); bisphenol AF (BPAF); bisphenol Z (BPZ); bisphenol B (BPB)] in 3 human breast cancer cell lines. Estrogenicity was assessed (10-11-10-4 M) by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element-mediated transcription in a luciferase assay. BPAF was the most potent bisphenol, followed by BPB > BPZ ∼ BPA > BPF ∼ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs. Data mining of ToxCast high-throughput screening assays confirm our results but also show divergence in the sensitivities of the assays. Gene expression profiles were determined in MCF-7 cells by microarray analysis. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by Illumina-based RNA sequencing. In conclusion, BPA alternatives are not necessarily less estrogenic than BPA in human breast cancer cells. BPAF, BPB, and BPZ were more estrogenic than BPA. These findings point to the importance of better understanding the risk of adverse effects from exposure to BPA alternatives, including hormone-dependent breast cancer.
- Published
- 2017
37. Correction of IVS I-110(GA) β-thalassemia by CRISPR/Cas-and TALEN-mediated disruption of aberrant regulatory elements in human hematopoietic stem and progenitor cells
- Author
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Michael Antoniou, Carsten W. Lederer, Panayiota Papasavva, Constantinos Christos Loucari, Toni Cathomen, Giandomenico Turchiano, Marina Kleanthous, Soteroulla Christou, Tatjana I. Cornu, Maria Sitarou, Claudio Mussolino, Coralea Stephanou, Petros Patsali, and Marianna Romito
- Subjects
Thalassemia ,beta-Globins ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Genome editing ,Transcription Activator-Like Effector Nucleases ,medicine ,CRISPR ,Humans ,Progenitor cell ,Online Only Articles ,030304 developmental biology ,Gene Editing ,0303 health sciences ,Transcription activator-like effector nuclease ,Base Sequence ,beta-Thalassemia ,Hematopoietic stem cell ,High-Throughput Nucleotide Sequencing ,Hematology ,Genetic Therapy ,medicine.disease ,Hematopoietic Stem Cells ,Introns ,Cell biology ,Haematopoiesis ,medicine.anatomical_structure ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,RNA splicing ,Mutation ,CRISPR-Cas Systems - Published
- 2019
38. Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa
- Author
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Michael Antoniou, Sophia Aristodemou, Alain Hovnanian, Christos Georgiadis, Mei Chen, Su M. Lwin, M. Titeux, S. Miskinyte, Rashida Pramanik, Waseem Qasim, Lucas Chan, Rachel Phillips, Jakub Tolar, Wei Li Di, John A. McGrath, Adrian J. Thrasher, Christos Tziotzios, Linda Ozoemena, Alyson Guy, Alya Abdul-Wahab, Fiona Reid, James R. McMillan, Magdalena Martinez-Queipo, Lu Liu, Fernando Larcher, Jemima E. Mellerio, Johann W. Bauer, Patricia A. Lovell, Marcela Del Rio, Sonia Serrano, Clarisse Maurin, Anastasia Petrova, Farhatullah Syed, Alexandros Onoufriadis, Tendai Kadiyirire, Ellie Rashidghamat, Maria Elstad, Racheal Rowles, Farzin Farzaneh, John B. Mee, and Elizabeth Orrin
- Subjects
Male ,0301 basic medicine ,Pathology ,Genetic enhancement ,Research & Experimental Medicine ,law.invention ,0302 clinical medicine ,law ,COL7A1 ,REAL-TIME PCR ,General Medicine ,Middle Aged ,Epidermolysis Bullosa Dystrophica ,Treatment Outcome ,medicine.anatomical_structure ,Medicine, Research & Experimental ,030220 oncology & carcinogenesis ,Recombinant DNA ,Female ,Life Sciences & Biomedicine ,Genetic diseases ,Adult ,CELL THERAPY ,EXPRESSION ,medicine.medical_specialty ,VII COLLAGEN ,Collagen Type VII ,Transgene ,Dermatology ,DIAGNOSIS ,03 medical and health sciences ,Gene therapy ,In vivo ,Complementary DNA ,Anchoring fibrils ,medicine ,Genetics ,Humans ,Fibroblast ,Basement membrane ,Science & Technology ,business.industry ,TRANSPLANTATION ,Lentivirus ,KERATINOCYTES ,Genetic Therapy ,Fibroblasts ,030104 developmental biology ,Clinical Medicine ,INJECTION ,business ,SKIN - Abstract
BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of skin fragility disorder due to mutations in COL7A1 encoding basement membrane type VII collagen (C7), the main constituent of anchoring fibrils (AFs) in skin. We developed a self-inactivating lentiviral platform encoding a codon-optimized COL7A1 cDNA under the control of a human phosphoglycerate kinase promoter for phase I evaluation. METHODS: In this single-center, open-label phase I trial, 4 adults with RDEB each received 3 intradermal injections (~1 × 10(6) cells/cm(2) of intact skin) of COL7A1-modified autologous fibroblasts and were followed up for 12 months. The primary outcome was safety, including autoimmune reactions against recombinant C7. Secondary outcomes included C7 expression, AF morphology, and presence of transgene in the injected skin. RESULTS: Gene-modified fibroblasts were well tolerated, without serious adverse reactions or autoimmune reactions against recombinant C7. Regarding efficacy, there was a significant (P < 0.05) 1.26-fold to 26.10-fold increase in C7 mean fluorescence intensity in the injected skin compared with noninjected skin in 3 of 4 subjects, with a sustained increase up to 12 months in 2 of 4 subjects. The presence of transgene (codon-optimized COL7A1 cDNA) was demonstrated in the injected skin at month 12 in 1 subject, but no new mature AFs were detected. CONCLUSION: To our knowledge, this is the first human study demonstrating safety and potential efficacy of lentiviral fibroblast gene therapy with the presence of COL7A1 transgene and subsequent C7 restoration in vivo in treated skin at 1 year after gene therapy. These data provide a rationale for phase II studies for further clinical evaluation. TRIAL REGISTRATION: ClincalTrials.gov NCT02493816. FUNDING: Cure EB, Dystrophic Epidermolysis Bullosa Research Association (UK), UK NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, and Fondation René Touraine Short-Exchange Award.
- Published
- 2019
39. Insight into the confusion over surfactant co-formulants in glyphosate-based herbicides
- Author
-
Charles Benbrook, Robin Mesnage, and Michael Antoniou
- Subjects
Active ingredient ,Herbicides ,Glycine ,Glyphosate based herbicides ,General Medicine ,Pesticide ,Toxicology ,Risk Assessment ,First generation ,Quaternary Ammonium Compounds ,chemistry.chemical_compound ,Surface-Active Agents ,chemistry ,Pulmonary surfactant ,Glyphosate ,Environmental chemistry ,medicine ,media_common.cataloged_instance ,European union ,medicine.symptom ,Amines ,Ecosystem ,Food Science ,media_common ,Confusion - Abstract
Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs). Other chemicals in GBHs are presumed as inert by regulatory authorities and are largely ignored in pesticide safety evaluations. We identified the surfactants in a cross-section of GBH formulations and compared their acute toxic effects. The first generation of polyethoxylated amine (POEA) surfactants (POE-tallowamine) in Roundup are markedly more toxic than glyphosate and heightened concerns of risks to human health, especially among heavily-exposed applicators. Beginning in the mid-1990s, first-generation POEAs were progressively replaced by other POEA surfactants, ethoxylated etheramines, which exhibited lower non-target toxic effects. Lingering concern over surfactant toxicity was mitigated at least in part within the European Union by the introduction of propoxylated quaternary ammonium surfactants. This class of POEA surfactants are ∼100 times less toxic to aquatic ecosystems and human cells than previous GBH-POEA surfactants. As GBH composition is legally classified as confidential commercial information, confusion concerning the identity and concentrations of co-formulants is common and descriptions of test substances in published studies are often erroneous or incomplete. In order to resolve this confusion, laws requiring disclosure of the chemical composition of pesticide products could be enacted. Research to understand health implications from ingesting these substances is required.
- Published
- 2019
40. An imazamox-based herbicide causes apoptotic changes in rat liver and pancreas
- Author
-
Aristidis Tsatsakis, Leda Kovatsi, Robin Mesnage, Tatyana I. Burykina, Cigdem Sevim, Selim Çomaklı, Alexandra Kalogeraki, Ali Taghizadehghalehjoughi, Mustafa Özkaraca, and Michael Antoniou
- Subjects
medicine.medical_specialty ,Imazamox ,Health, Toxicology and Mutagenesis ,chemistry.chemical_element ,Caspase 3 ,In situ hybridization ,010501 environmental sciences ,Calcium ,Toxicology ,01 natural sciences ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:RA1190-1270 ,Internal medicine ,medicine ,Cytotoxicity ,ComputingMethodologies_COMPUTERGRAPHICS ,0105 earth and related environmental sciences ,lcsh:Toxicology. Poisons ,Creatinine ,Chemistry ,Anti-insulin ,Immunohistochemistry ,Acute toxicity ,medicine.anatomical_structure ,Endocrinology ,Apoptosis ,Pancreas ,030217 neurology & neurosurgery - Abstract
Graphical abstract, Highlights • Toxicity of an imazamox-based herbicide was evaluated in rats. • Blood samples were collected and serum ALP, AST, glucose, calcium and creatinine levels were determined. • Imazamox formulation induced an increase in serum glucose and calcium. • Liver and pancreatic tissue were studied by immunohistochemistry and in-situ hybridization. • Necrotic and degenerative changes were observed in insulin positive ß cells., We studied the acute toxicity of an imazamox-based herbicide at 12, 24 and 36 mg/kg body (bw) weight imazamox equivalent dose on the liver and pancreatic tissue in Sprague Dawley rats. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, glucose, calcium as well as creatinine, were determined in blood samples, which were collected after 24, 48 and 72 h exposure. Caspase 3 and anti-insulin expression and immunopositivity were evaluated using in situ hybridization and immunohistochemistry, respectively. The imazamox-based herbicide evaluated in this study induced toxic effects even from the lowest dose tested (12 mg/kg bw). The two highest doses caused a statistically significant cytotoxicity on the Langerhans islet cells. Necrotic and degenerative changes were detected in hepatocytes at the two highest doses. Imazamox is considered to be poorly toxic to the liver. Nevertheless, the imazamox-based herbicide formulation tested here reduced the size of the β-islet cells, induced an elevation in serum glucose and calcium. Our data shows that commercial formulations of imazamox containing various co-formulants can have hepatic and pancreatic toxic effects.
- Published
- 2019
41. Relationship between faecal microbiota and plasma metabolome in rats fed NK603 and MON810 GM maize from the GMO90+ study
- Author
-
Michael Antoniou, Bernard Salles, Martina Biserni, Caroline I. Le Roy, Robin Mesnage, Faculty of life Sciences and Medicine, Department of Twin Research and Genetic Epidemiology, King's College London, London, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), and Sustainable Food Alliance (USA)
- Subjects
Male ,MON 810 ,Food, Genetically Modified ,metabolite ,microbiome ,[SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain ,010501 environmental sciences ,Toxicology ,medicine.disease_cause ,Coriobacteriaceae ,01 natural sciences ,Zea mays ,03 medical and health sciences ,Feces ,Metabolomics ,fluids and secretions ,glyphosate ,RNA, Ribosomal, 16S ,medicine ,Metabolome ,Animals ,Microbiome ,Food science ,Rats, Wistar ,030304 developmental biology ,0105 earth and related environmental sciences ,Bifidobacterium ,2. Zero hunger ,0303 health sciences ,biology ,Toxin ,GMO ,Ruminococcus ,food and beverages ,General Medicine ,biology.organism_classification ,Plants, Genetically Modified ,Genetically modified organism ,Diet ,Gastrointestinal Microbiome ,NK603 ,RNA, Bacterial ,Composition (visual arts) ,Female ,Food Science - Abstract
Safety concerns arising from the consumption of foods derived from genetically modified (GM) crops remains a highly debated and controversial subject. We report here a faecal microbiota compositional analysis in Wistar rats from the GMO90+ study, which fed glyphosate-tolerant NK603 (+/− Roundup application during cultivation) and Bt toxin MON810 GM maize for 6 months (at 11 and 33% composition of the feed) in comparison to their closest non-GM isogenic lines. We first integrated the faecal microbiota compositional data with results from plasma metabolomics to establish a baseline allowing us to understand which bacterial species can influence host metabolism.CoriobacteriaceaeandAcetatifactorsignificantly predicted plasma metabolic profile in males, whileBifidobacteriumandRuminococcuswere able to predict female plasma metabolites. We then investigated the differences in fecal microbiota composition between group of rats fed MON810 or NK603 GM maize varieties in comparison to their respective isogenic lines. Bacterial community richness was not altered by the test diets. There were no statistically significant differences in taxa abundance in the rat faecal microbiota that we could attribute to the consumption of either MON810 or NK603 GM maize varieties. In conclusion, we show that the consumption of the widely cultivated GM maize varieties NK603 and MON810 even up to 33% of the total diet had no effect on the status of the faecal microbiota compared to non-GM near isogenic lines.
- Published
- 2019
42. Addressing concerns over the fate of DNA derived from genetically modified food in the human body: A review
- Author
-
Aristides M. Tsatsakis, Muhammad Amjad Nawaz, Michael Antoniou, Gyuhwa Chung, Kirill S. Golokhvast, Seung Hwan Yang, and Robin Mesnage
- Subjects
DNA, Plant ,Gene Transfer, Horizontal ,Somatic cell ,Transgene ,Food, Genetically Modified ,Biology ,Toxicology ,Transfection ,Genome ,Genetically modified food ,03 medical and health sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Gene expression ,Animals ,Humans ,Transgenes ,030304 developmental biology ,Genetics ,0303 health sciences ,digestive, oral, and skin physiology ,food and beverages ,04 agricultural and veterinary sciences ,General Medicine ,Plants, Genetically Modified ,040401 food science ,Genetically modified organism ,Gastrointestinal Tract ,MicroRNAs ,chemistry ,Gene Expression Regulation ,Horizontal gene transfer ,DNA ,Food Science - Abstract
Global commercialization of GM food and feed has stimulated much debate over the fate of GM food-derived DNA in the body of the consumer and as to whether it poses any health risks. We reviewed the fate of DNA derived from GM food in the human body. During mechanical/chemical processing, integrity of DNA is compromised. Food-DNA can survive harsh processing and digestive conditions with fragments up to a few hundred bp detectable in the gastrointestinal tract. Compelling evidence supported the presence of food (also GM food) derived DNA in the blood and tissues of human/animal. There is limited evidence of food-born DNA integrating into the genome of the consumer and of horizontal transfer of GM crop DNA into gut-bacteria. We find no evidence that transgenes in GM crop-derived foods have a greater propensity for uptake and integration than the host DNA of the plant-food. We found no evidence of plant-food DNA function/expression following transfer to either the gut-bacteria or somatic cells. Strong evidence suggested that plant-food-miRNAs can survive digestion, enter the body and affect gene expression patterns. We envisage that this multi-dimensional review will address questions regarding the fate of GM food-derived DNA and gene-regulatory-RNA in the human body.
- Published
- 2018
43. Relative and Absolute Quantification of Aberrant and Normal Splice Variants in HBBIVSI−110 (G > A) β-Thalassemia
- Author
-
Soteroulla Christou, Panayiota Papasavva, Petros Patsali, Maria Sitarou, Marina Kleanthous, Michael Antoniou, and Carsten W. Lederer
- Subjects
0301 basic medicine ,transcript variants ,Mutant ,absolute quantification ,Locus (genetics) ,splice defect ,Biology ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,splicing ,03 medical and health sciences ,0302 clinical medicine ,splice ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Gene ,Spectroscopy ,Messenger RNA ,Organic Chemistry ,Alternative splicing ,General Medicine ,Molecular biology ,3. Good health ,Computer Science Applications ,duplex quantitative PCR ,030104 developmental biology ,Real-time polymerase chain reaction ,lcsh:Biology (General) ,lcsh:QD1-999 ,β-thalassemia ,RNA splicing ,030215 immunology - Abstract
The β-thalassemias are an increasing challenge to health systems worldwide, caused by absent or reduced β-globin (HBB) production. Of particular frequency in many Western countries is HBBIVSI−110(G > A) β-thalassemia (HGVS name: HBB:c.93-21G > A). Its underlying mutation creates an abnormal splice acceptor site in the HBB gene, and while partially retaining normal splicing of HBB, it severely reduces HBB protein expression from the mutant locus and HBB loci in trans. For the assessment of the underlying mechanisms and of therapies targeting β-thalassemia, accurate quantification of aberrant and normal HBB mRNA is essential, but to date, has only been performed by approximate methods. To address this shortcoming, we have developed an accurate, duplex reverse-transcription quantitative PCR assay for the assessment of the ratio and absolute quantities of normal and aberrant mRNA species as a tool for basic and translational research of HBBIVSI−110(G > A) β-thalassemia. The method was employed here to determine mRNA ratios and quantities in blood and primary cell culture samples and correlate them with HBB protein levels. Moreover, with its immediate utility for β-thalassemia and the mutation in hand, the approach can readily be adopted for analysis of alternative splicing or for quantitative assays of any disease-causing mutation that interferes with normal splicing.
- Published
- 2020
44. Anthony Kyriacou Antoniou
- Author
-
Michael Antoniou, Nikolay Plotnikov, Demi Antoniou, Xanthe Antoniou-Plotnikova, and Anthony Antoniou-Plotnikov
- Subjects
Sadness ,Chose ,media_common.quotation_subject ,General practice ,Grammar school ,Subject (documents) ,General Medicine ,Sociology ,Classics ,media_common - Abstract
The death of Anthony Kyriacou Antoniou (“Tony”) on Monday, 2 December 2019, at the age of 80 from cancer has, with great sadness, extinguished the light of one of our leading internationally respected physicians in general practice. Tony was born on 15 September 1939 in Cyprus. He came to London with his family in 1951 and was educated at Quintin Kynaston Grammar School in St John’s Wood, London, which was originally in Marylebone. There at the grammar school he walked off with the top prizes in every subject except “woodwork and art.” His sole desire in life was to become a doctor of medicine. Tony chose University College Hospital because of its long history in life sciences and Nobel laureates. The net result of his …
- Published
- 2020
45. Reply to ‘Comments on two recent publications on GM maize and Roundup’
- Author
-
Sarah Zanon Agapito-Tenfen, Gilles-Eric Séralini, Robin Mesnage, and Michael Antoniou
- Subjects
Crops, Agricultural ,Proteomics ,0106 biological sciences ,0301 basic medicine ,Multidisciplinary ,lcsh:R ,lcsh:Medicine ,Diagnostic marker ,Plants, Genetically Modified ,Animal Feed ,Zea mays ,01 natural sciences ,Article ,Rats ,Epistemology ,03 medical and health sciences ,030104 developmental biology ,Rat liver ,Metabolomics ,Animals ,lcsh:Q ,lcsh:Science ,Psychology ,010606 plant biology & botany - Abstract
The opinion expressed by Eriksson and colleagues’ fails to recognise that there are no standard experimental designs for academic investigations involving omics analyses of genetically modified crops and that the only valid comparator to determine the effect of the process of transgenesis is a near isogenic variety grown at the same time and location, as was the case in our investigation of NK603 maize. Eriksson does not acknowledge that the quality of the rat liver tissues in our chronic Roundup toxicity study has neither been questioned nor branded as unsuitable for further investigation. In addition, Eriksson fails to appreciate that the statistical methods we used to analyse the liver metabolomics dataset are recognised as appropriate as some of a number of approaches that can be taken. Moreover, Eriksson neglects to mention that the proteomics analysis of the liver tissues highlights structural and functional damage from Roundup exposure. Thus our results are sound and the claims by Eriksson and colleagues of experimental flaws are unfounded.Replying to: Eriksson et al. Sci Rep 8 (2018); https://doi.org/10.1038/s41598-018-30440-7.
- Published
- 2018
46. Publisher Correction: In Utero Gene Therapy (IUGT) Using GLOBE Lentiviral Vector Phenotypically Corrects the Heterozygous Humanised Mouse Model and Its Progress Can Be Monitored Using MRI Techniques
- Author
-
Simon N. Waddington, Panicos Shangaris, Durrgah L. Ramachandra, Daniel J. Stuckey, Wei Wang, Nahla Bakhamis, Adrian J. Thrasher, Simon Eaton, Ayad Eddaoudi, Anna L. David, S Subramaniam, Christina Flouri, Stavros P. Loukogeorgakis, Joy Archer, Paolo De Coppi, Michael Antoniou, Manfred G. Schmidt, Shanrun Liu, Laurence H. Jackson, Michael P. Blundell, Luca Urbani, Thomas M. Ryan, and Panagiotis Maghsoudlou
- Subjects
Mri techniques ,Pathology ,medicine.medical_specialty ,Multidisciplinary ,business.industry ,Genetic enhancement ,Science ,Viral vector ,In utero ,Medicine ,business - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2019
47. Author Correction: Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide
- Author
-
Gilles-Eric Séralini, Michael Antoniou, Malcolm Ward, George Renney, and Robin Mesnage
- Subjects
0301 basic medicine ,Chronic exposure ,medicine.medical_specialty ,Multidisciplinary ,Ultra low dose ,business.industry ,Science ,Fatty liver ,Non alcoholic ,Disease ,010501 environmental sciences ,medicine.disease ,01 natural sciences ,Gastroenterology ,03 medical and health sciences ,030104 developmental biology ,Internal medicine ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,medicine ,Medicine ,business ,Author Correction ,0105 earth and related environmental sciences - Abstract
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
- Published
- 2018
48. Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in HepaRG liver cells exposed to PCB 126
- Author
-
Eva Wozniak, Clément Frainay, Nathalie Poupin, Charles A. Mein, Robin Mesnage, Fabien Jourdan, Sucharitha Balu, Theodoros Xenakis, Michael Antoniou, Martina Biserni, Department of Medical and Molecular Genetics, King‘s College London, Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Barts and The London School of Medicine and Dentistry, and Sustainable Food Alliance (USA)
- Subjects
0301 basic medicine ,Health, Toxicology and Mutagenesis ,010501 environmental sciences ,Toxicology ,medicine.disease_cause ,liver ,01 natural sciences ,Cell Line ,Transcriptome ,03 medical and health sciences ,Metabolomics ,Molecular Toxicology ,Non-alcoholic Fatty Liver Disease ,NAFLD ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Metabolome ,Humans ,030304 developmental biology ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,0303 health sciences ,PCB ,Liver cell ,Gene Expression Profiling ,Fatty liver ,Lipid metabolism ,General Medicine ,Lipid Metabolism ,medicine.disease ,Polychlorinated Biphenyls ,3. Good health ,030104 developmental biology ,Receptors, Aryl Hydrocarbon ,Biochemistry ,chemistry ,13. Climate action ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,Inactivation, Metabolic ,metabolome ,Steatosis ,HepaRG ,transcriptome ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Oxidative stress ,Polyunsaturated fatty acid - Abstract
Chemical pollutant exposure is a risk factor contributing to the growing epidemic of non-alcoholic fatty liver disease (NAFLD) affecting human populations that consume a western diet. Although it is recognized that intoxication by chemical pollutants can lead to NAFLD, there is limited information available regarding the mechanism by which typical environmental levels of exposure can contribute to the onset of this disease. Here, we describe the alterations in gene expression profiles and metabolite levels in the human HepaRG liver cell line, a validated model for cellular steatosis, exposed to the polychlorinated biphenyl (PCB) 126, one of the most potent chemical pollutants that can induce NAFLD. Sparse partial least squares classification of the molecular profiles revealed that exposure to PCB 126 provoked a decrease in polyunsaturated fatty acids as well as an increase in sphingolipid levels, concomitant with a decrease in the activity of genes involved in lipid metabolism. This was associated with an increased oxidative stress reflected by marked disturbances in taurine metabolism. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. These changes in metabolome and transcriptome profiles were observed even at the lowest concentration (100 pM) of PCB 126 tested. A decrease in docosatrienoate levels was the most sensitive biomarker. Overall, our integrated multi-omics analysis provides mechanistic insight into how this class of chemical pollutant can cause NAFLD. Our study lays the foundation for the development of molecular signatures of toxic effects of chemicals causing fatty liver diseases to move away from a chemical risk assessment based on in vivo animal experiments. Electronic supplementary material The online version of this article (10.1007/s00204-018-2235-7) contains supplementary material, which is available to authorized users.
- Published
- 2018
49. OBSOLETE: Round-up ready! Glyphosate and the current controversy over the world's leading herbicide
- Author
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Michael Antoniou and Robin Mesnage
- Subjects
chemistry.chemical_compound ,Engineering ,Agronomy ,chemistry ,Genetically engineered ,business.industry ,Glyphosate ,business - Abstract
Glyphosate-based herbicides (GBHs) are the most heavily applied in the world and usage continues to rise exponentially since the introduction of Roundup Ready crops, a series of crop varieties genetically engineered to be sprayed with GBHs such as Roundup® without dying. As a result, glyphosate is found virtually everywhere in the food chain. An intense debate on its toxicity, in particular its carcinogenic potential, is raging at the time of the review of this compound for re-registration (2017) in both Europe and the United States.
- Published
- 2018
50. Author Correction: An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process
- Author
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Michael Antoniou, Malcolm Ward, Robin Mesnage, George Renney, Vinicius Vilperte, Sarah Zanon Agapito-Tenfen, Gilles-Eric Séralini, and Rubens Onofre Nodari
- Subjects
Multidisciplinary ,Process (engineering) ,Computer science ,Mathematics::History and Overview ,lcsh:R ,lcsh:Medicine ,Computational biology ,Transformation (music) ,Physics::History of Physics ,Computer Science::Discrete Mathematics ,Data_FILES ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Multi omics ,lcsh:Q ,lcsh:Science ,Computer Science::Distributed, Parallel, and Cluster Computing ,Computer Science::Databases - Abstract
A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
- Published
- 2019
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