Journal Description
Toxins
Toxins
is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to toxinology and all kinds of toxins (biotoxins) from animals, microbes and plants. Toxins is published monthly online by MDPI. The French Society on Toxinology (SFET), International Society for Mycotoxicology (ISM), Japanese Society of Mycotoxicology (JSMYCO) and European Uremic Toxins (EUTox) Work Group are affiliated with Toxins and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, CAPlus / SciFinder, AGRIS, and other databases.
- Journal Rank: JCR - Q1 (Toxicology) / CiteScore - Q1 (Toxicology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.4 days after submission; acceptance to publication is undertaken in 3.2 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 6 topical sections.
Impact Factor:
4.2 (2022);
5-Year Impact Factor:
4.7 (2022)
Latest Articles
Paradoxical Exception to Island Tameness: Increased Defensiveness in an Insular Population of Rattlesnakes
Toxins 2024, 16(3), 157; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030157 - 18 Mar 2024
Abstract
Island tameness results largely from a lack of natural predators. Because some insular rattlesnake populations lack functional rattles, presumably the consequence of relaxed selection from reduced predation, we hypothesized that on Santa Catalina Island, California, USA, populations of the southern Pacific rattlesnake (
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Island tameness results largely from a lack of natural predators. Because some insular rattlesnake populations lack functional rattles, presumably the consequence of relaxed selection from reduced predation, we hypothesized that on Santa Catalina Island, California, USA, populations of the southern Pacific rattlesnake (Crotalus helleri), which possesses functional rattles, would exhibit a decrement in defensive behavior relative to their mainland counterparts. Contrary to our prediction, rattlesnakes from the island not only lacked tameness compared to mainland snakes, but instead exhibited measurably greater levels of defensiveness. Island snakes attempted to bite 4.7 times more frequently as we endeavored to secure them by hand, and required 2.1-fold more time to be pinned and captured. When induced to bite a beaker after being grasped, the island snakes also delivered 2.1-fold greater quantities of venom when controlling for body size. The additional venom resulted from 2.1-fold larger pulses of venom ejected from the fangs. We found no effects of duration in captivity (2–36 months), which suggests an absence of long-term habituation of antipredator behaviors. Breeding bird surveys and Christmas bird counts indicated reduced population densities of avian predators on Catalina compared to the mainland. However, historical estimates confirmed that populations of foxes and introduced mammalian predators (cats and pigs) and antagonists (herbivorous ungulates) substantially exceeded those on the mainland in recent centuries, and therefore best explain the paradoxically exaggerated defensive behaviors exhibited by Catalina’s rattlesnakes. These findings augment our understanding of anthropogenic effects on the behaviors of island animals and underscore how these effects can negatively affect human safety.
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(This article belongs to the Section Animal Venoms)
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Cationicity Enhancement on the Hydrophilic Face of Ctriporin Significantly Reduces Its Hemolytic Activity and Improves the Antimicrobial Activity against Antibiotic-Resistant ESKAPE Pathogens
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Xudong Luo, Huan Deng, Li Ding, Xiangdong Ye, Fang Sun, Chenhu Qin and Zongyun Chen
Toxins 2024, 16(3), 156; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030156 - 18 Mar 2024
Abstract
The ESKAPE pathogen-associated antimicrobial resistance is a global public health issue, and novel therapeutic strategies are urgently needed. The short cationic antimicrobial peptide (AMP) family represents an important subfamily of scorpion-derived AMPs, but high hemolysis and poor antimicrobial activity hinder their therapeutic application.
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The ESKAPE pathogen-associated antimicrobial resistance is a global public health issue, and novel therapeutic strategies are urgently needed. The short cationic antimicrobial peptide (AMP) family represents an important subfamily of scorpion-derived AMPs, but high hemolysis and poor antimicrobial activity hinder their therapeutic application. Here, we recomposed the hydrophilic face of Ctriporin through lysine substitution. We observed non-linear correlations between the physiochemical properties of the peptides and their activities, and significant deviations regarding the changes of antimicrobial activities against different bacterial species, as well as hemolytic activity. Most importantly, we obtained two Ctriporin analogs, CM5 and CM6, these two have significantly reduced hemolytic activity and more potent antimicrobial activities against all tested antibiotic-resistant ESKAPE pathogens. Fluorescence experiments indicated they may perform the bactericidal function through a membrane-lytic action model. Our work sheds light on the potential of CM5 and CM6 in developing novel antimicrobials and gives clues for optimizing peptides from the short cationic AMP family.
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(This article belongs to the Section Animal Venoms)
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Open AccessArticle
Unveiling the Diversity and Modifications of Short Peptides in Buthus martensii Scorpion Venom through Liquid Chromatography-High Resolution Mass Spectrometry
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Ling Zeng, Cangman Zhang, Mingrong Yang, Jianfeng Sun, Jingguang Lu, Huixia Zhang, Jianfeng Qin, Wei Zhang and Zhihong Jiang
Toxins 2024, 16(3), 155; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030155 - 16 Mar 2024
Abstract
More recently, short peptides in scorpion venom have received much attention because of their potential for drug discovery. Although various biological effects of these short peptides have been found, their studies have been hindered by the lack of structural information especially in modifications.
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More recently, short peptides in scorpion venom have received much attention because of their potential for drug discovery. Although various biological effects of these short peptides have been found, their studies have been hindered by the lack of structural information especially in modifications. In this study, small peptides from scorpion venom were investigated using high-performance liquid chromatography high-resolution mass spectrometry followed by de novo sequencing. A total of 156 sequences consisting of 2~12 amino acids were temporarily identified from Buthus martensii scorpion venom. The identified peptides exhibited various post-translational modifications including N-terminal and C-terminal modifications, in which the N-benzoyl modification was first found in scorpion venom. Moreover, a short peptide Bz-ARF-NH2 demonstrated both N-terminal and C-terminal modifications simultaneously, which is extremely rare in natural peptides. In conclusion, this study provides a comprehensive insight into the diversity, modifications, and potential bioactivities of short peptides in scorpion venom.
Full article
(This article belongs to the Special Issue Toxinology of Arthropod Venom Peptides: Chemical and Biomedical Investigation)
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Open AccessArticle
The Effects of T-2 Toxin, Deoxynivalenol, and Fumonisin B1 on Oxidative Stress-Related Genes in the Kidneys of Laying Hens
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Benjamin Kövesi, Szabina Kulcsár, Zsolt Ancsin, Márta Erdélyi, Erika Zándoki, Patrik Gömbös, Krisztián Balogh and Miklós Mézes
Toxins 2024, 16(3), 154; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030154 - 16 Mar 2024
Abstract
In the context of nephrotoxic risks associated with environmental contaminants, this study focused on the impact of mycotoxin exposure on the renal health of laying hens, with particular attention to oxidative stress pathways. Sixty laying hens were assigned to three groups—a control group
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In the context of nephrotoxic risks associated with environmental contaminants, this study focused on the impact of mycotoxin exposure on the renal health of laying hens, with particular attention to oxidative stress pathways. Sixty laying hens were assigned to three groups—a control group (CON), a low-dose mycotoxin group (LOW), and a high-dose mycotoxin group (HIGH)—and monitored for 72 h. Mycotoxin contamination involved T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 at their EU-recommended levels (low mix) and at double doses (high mix). Clinical assessments revealed no signs of toxicity or notable weight changes. Analysis of the glutathione redox system parameters demonstrated that the reduced glutathione content was lower than that in the controls at 48 h and higher at 72 h. Glutathione peroxidase activity increased in response to mycotoxin exposure. In addition, the gene expression patterns of key redox-sensitive pathways, including Keap1-Nrf2-ARE and the AhR pathway, were examined. Notably, gene expression profiles revealed dynamic responses to mycotoxin exposure over time, underscoring the intricate interplay of redox-related mechanisms in the kidney. This study sheds light on the early effects of mycotoxin mixtures on laying hens’ kidneys and their potential for oxidative stress.
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(This article belongs to the Section Mycotoxins)
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Open AccessSystematic Review
Botulinum Toxin for Pain Relief in Cancer Patients: A Systematic Review of Randomized Controlled Trials
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Lorenzo Lippi, Alessandro de Sire, Alessio Turco, Martina Ferrillo, Serdar Kesikburun, Alessio Baricich, Stefano Carda and Marco Invernizzi
Toxins 2024, 16(3), 153; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030153 - 15 Mar 2024
Abstract
Cancer pain is one of the most disabling symptoms complained by cancer patients, with a crucial impact on physical and psychological well-being. Botulinum neurotoxins (BoNTs) type A and B have emerged as potential interventions for chronic pain; however, their role in these patients
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Cancer pain is one of the most disabling symptoms complained by cancer patients, with a crucial impact on physical and psychological well-being. Botulinum neurotoxins (BoNTs) type A and B have emerged as potential interventions for chronic pain; however, their role in these patients is still debated. Thus, this systematic review of randomized controlled trials aimed at assessing the effects of BoNT treatment for cancer pain to guide physicians in an evidence-based approach integrating BoNT in cancer care. Out of 5824 records, 10 RCTs satisfied our eligibility criteria and were included in the present work for a total of 413 subjects with several cancer types (breast, head and neck, esophageal, and thoracic/gastric cancers). While some studies demonstrated significant pain reduction and improved quality of life post-BoNT-A injections, outcomes across different cancer types were inconclusive. Additionally, several effects were observed in functioning, dysphagia, salivary outcomes, esophageal strictures, gastric emptying, and expansions. This review emphasizes the need for further standardized research to conclusively establish the efficacy of BoNT in comprehensive cancer pain management.
Full article
(This article belongs to the Special Issue Uses of Botulinum Toxin Injection in Medicine)
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Open AccessArticle
Immunochemical Recognition of Bothrops rhombeatus Venom by Two Polyvalent Antivenoms
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Karen Sarmiento, Jorge Zambrano, Carlos Galvis, Álvaro Molina-Olivares, Marisol Margarita Villadiego-Molinares, Johanna Alejandra Ramírez-Martínez, Ana Lucía Castiblanco and Fabio A. Aristizabal
Toxins 2024, 16(3), 152; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030152 - 15 Mar 2024
Abstract
The protein profile of Bothrops rhombeatus venom was compared to Bothrops asper and Bothrops atrox, and the effectiveness of antivenoms from the National Institute of Health of Colombia (INS) and Antivipmyn-Tri (AVP-T) of Mexico were analyzed. Protein profiles were studied with sodium dodecyl
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The protein profile of Bothrops rhombeatus venom was compared to Bothrops asper and Bothrops atrox, and the effectiveness of antivenoms from the National Institute of Health of Colombia (INS) and Antivipmyn-Tri (AVP-T) of Mexico were analyzed. Protein profiles were studied with sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and reverse-phase high-performance liquid chromatography (RP-HPLC). The neutralizing potency and the level of immunochemical recognition of the antivenoms to the venoms were determined using Western blot, affinity chromatography, and enzyme-linked immunosorbent assay (ELISA). Bands of phospholipase A2 (PLA2), metalloproteinases (svMPs) I, II, and III as well as serine proteinases (SPs) in the venom of B. rhombeatus were recognized by SDS-PAGE. With Western blot, both antivenoms showed immunochemical recognition towards PLA2 and svMP. INS showed 94% binding to B. rhombeatus venom and 92% to B. asper while AVP-T showed 90.4% binding to B. rhombeatus venom and 96.6% to B. asper. Both antivenoms showed binding to PLA2 and svMP, with greater specificity of AVP-T towards B. rhombeatus. Antivenom neutralizing capacity was calculated by species and mL of antivenom, finding the following for INS: B. asper 6.6 mgV/mL, B. atrox 5.5 mgV/mL, and B. rhombeatus 1.3 mgV/mL. Meanwhile, for AVP-T, the following neutralizing capacities were found: B. asper 2.7 mgV/mL, B. atrox 2.1 mgV/mL, and B. rhombeatus 1.4 mgV/mL. These results show that both antivenoms presented similarity between calculated neutralizing capacities in our trial, reported in a product summary for the public for the B. asper species; however, this does not apply to the other species tested in this trial.
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(This article belongs to the Special Issue Proteomic Analysis and Functional Characterization of Venom)
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Open AccessArticle
Red Orange and Lemon Extract Ameliorates the Renal Oxidative Stress and Inflammation Induced by Ochratoxin A through the Modulation of Nrf2
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Consiglia Longobardi, Sara Damiano, Simona Fabroni, Serena Montagnaro, Valeria Russo, Emanuela Vaccaro, Antonio Giordano, Salvatore Florio and Roberto Ciarcia
Toxins 2024, 16(3), 151; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030151 - 14 Mar 2024
Abstract
Background: The presence of ochratoxin A (OTA) in food and feed is a public health concern. OTA intoxication is caused by several mechanisms, one of which consists of the alteration of the antioxidant activity of the cell due to the oxidative stress (OS).
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Background: The presence of ochratoxin A (OTA) in food and feed is a public health concern. OTA intoxication is caused by several mechanisms, one of which consists of the alteration of the antioxidant activity of the cell due to the oxidative stress (OS). In this context, the use of natural antioxidant substances could be a potential biological decontamination method of mitigating the negative outcomes induced by OTA. Methods: we aimed to investigate how a red orange and lemon extract (RLE), rich in anthocyanins, would affect OTA-treated rats. The current work sought to clarify the renal protective efficacy of RLE in an OTA-treated rat model (RLE (90 mg/kg b.w.); OTA (0.5 mg/kg b.w.)) by investigating, thorough Western blot analysis, the involvement of the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. The OS parameters and inflammatory status were evaluated by spectrophotometry. The inflammatory infiltrates in the kidney were evaluated by immunohistochemical assays. Results and Conclusion: Our findings showed a significant increase in oxidative and inflammatory parameters after OTA exposure, while the OTA + RLE co-treatment counteracted both the inflammatory and OS damage through the modulation of the Nrf2 pathway.
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(This article belongs to the Section Mycotoxins)
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Open AccessFeature PaperArticle
Diversity and Molecular Evolution of Antimicrobial Peptides in Caecilian Amphibians
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Mario Benítez-Prián, Héctor Lorente-Martínez, Ainhoa Agorreta, David J. Gower, Mark Wilkinson, Kim Roelants and Diego San Mauro
Toxins 2024, 16(3), 150; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030150 - 14 Mar 2024
Abstract
Antimicrobial peptides (AMPs) are key molecules in the innate immune defence of vertebrates with rapid action, broad antimicrobial spectrum, and ability to evade pathogen resistance mechanisms. To date, amphibians are the major group of vertebrates from which most AMPs have been characterised, but
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Antimicrobial peptides (AMPs) are key molecules in the innate immune defence of vertebrates with rapid action, broad antimicrobial spectrum, and ability to evade pathogen resistance mechanisms. To date, amphibians are the major group of vertebrates from which most AMPs have been characterised, but most studies have focused on the bioactive skin secretions of anurans (frogs and toads). In this study, we have analysed the complete genomes and/or transcriptomes of eight species of caecilian amphibians (order Gymnophiona) and characterised the diversity, molecular evolution, and antimicrobial potential of the AMP repertoire of this order of amphibians. We have identified 477 candidate AMPs within the studied caecilian genome and transcriptome datasets. These candidates are grouped into 29 AMP families, with four corresponding to peptides primarily exhibiting antimicrobial activity and 25 potentially serving as AMPs in a secondary function, either in their entirety or after cleavage. In silico prediction methods were used to identify 62 of those AMPs as peptides with promising antimicrobial activity potential. Signatures of directional selection were detected for five candidate AMPs, which may indicate adaptation to the different selective pressures imposed by evolutionary arms races with specific pathogens. These findings provide encouraging support for the expectation that caecilians, being one of the least-studied groups of vertebrates, and with ~300 million years of separate evolution, are an underexplored resource of great pharmaceutical potential that could help to contest antibiotic resistance and contribute to biomedical advance.
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(This article belongs to the Section Animal Venoms)
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Integration of Multi-Omics, Histological, and Biochemical Analysis Reveals the Toxic Responses of Nile Tilapia Liver to Chronic Microcystin-LR Exposure
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Yichao Li, Huici Yang, Bing Fu, Gen Kaneko, Hongyan Li, Jingjing Tian, Guangjun Wang, Mingken Wei, Jun Xie and Ermeng Yu
Toxins 2024, 16(3), 149; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030149 - 14 Mar 2024
Abstract
Microcystin-LR (MC-LR) is a cyanobacterial metabolite produced during cyanobacterial blooms and is toxic to aquatic animals, and the liver is the main targeted organ of MC-LR. To comprehensively understand the toxicity mechanism of chronic exposure to environmental levels of MC-LR on the liver
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Microcystin-LR (MC-LR) is a cyanobacterial metabolite produced during cyanobacterial blooms and is toxic to aquatic animals, and the liver is the main targeted organ of MC-LR. To comprehensively understand the toxicity mechanism of chronic exposure to environmental levels of MC-LR on the liver of fish, juvenile Nile tilapia were exposed to 0 μg/L (control), 1 μg/L (M1), 3 μg/L (M3), 10 μg/L (M10), and 30 μg/L (M30) MC-LR for 60 days. Then, the liver hepatotoxicity induced by MC-LR exposure was systematically evaluated via histological and biochemical determinations, and the underlying mechanisms were explored through combining analysis of biochemical parameters, multi-omics (transcriptome and metabolome), and gene expression. The results exhibited that chronic MC-LR exposure caused slight liver minor structural damage and lipid accumulation in the M10 group, while resulting in serious histological damage and lipid accumulation in the M30 group, indicating obvious hepatotoxicity, which was confirmed by increased toxicity indexes (i.e., AST, ALT, and AKP). Transcriptomic and metabolomic analysis revealed that chronic MC-LR exposure induced extensive changes in gene expression and metabolites in six typical pathways, including oxidative stress, apoptosis, autophagy, amino acid metabolism, primary bile acid biosynthesis, and lipid metabolism. Taken together, chronic MC-LR exposure induced oxidative stress, apoptosis, and autophagy, inhibited primary bile acid biosynthesis, and caused fatty deposition in the liver of Nile tilapia.
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(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)
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Open AccessArticle
Development of a Rapid and Sensitive CANARY Biosensor Assay for the Detection of Shiga Toxin 2 from Escherichia coli
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Christina C. Tam, Yangyang Wang, Wen-Xian Du, Andrew R. Flannery and Xiaohua He
Toxins 2024, 16(3), 148; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030148 - 14 Mar 2024
Abstract
Shiga-toxin-producing Escherichia coli (STEC) causes a wide spectrum of diseases including hemorrhagic colitis and hemolytic uremic syndrome (HUS). The current Food Safety Inspection Service (FSIS) testing methods for STEC use the Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) protocol, which includes
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Shiga-toxin-producing Escherichia coli (STEC) causes a wide spectrum of diseases including hemorrhagic colitis and hemolytic uremic syndrome (HUS). The current Food Safety Inspection Service (FSIS) testing methods for STEC use the Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) protocol, which includes enrichment, cell plating, and genomic sequencing and takes time to complete, thus delaying diagnosis and treatment. We wanted to develop a rapid, sensitive, and potentially portable assay that can identify STEC by detecting Shiga toxin (Stx) using the CANARY (Cellular Analysis and Notification of Antigen Risks and Yields) B-cell based biosensor technology. Five potential biosensor cell lines were evaluated for their ability to detect Stx2. The results using the best biosensor cell line (T5) indicated that this biosensor was stable after reconstitution with assay buffer covered in foil at 4 °C for up to 10 days with an estimated limit of detection (LOD) of ≈0.1–0.2 ng/mL for days up to day 5 and ≈0.4 ng/mL on day 10. The assay detected a broad range of Stx2 subtypes, including Stx2a, Stx2b, Stx2c, Stx2d, and Stx2g but did not cross-react with closely related Stx1, abrin, or ricin. Additionally, this assay was able to detect Stx2 in culture supernatants of STEC grown in media with mitomycin C at 8 and 24 h post-inoculation. These results indicate that the STEC CANARY biosensor developed in this study is sensitive, reproducible, specific, rapid (≈3 min), and may be applicable for surveillance of the environment and food to protect public health.
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(This article belongs to the Special Issue Foodborne Toxins and Public Health)
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Open AccessConference Report
Report from the 29th Meeting on Toxinology, “Toxins: From the Wild to the Lab”, Organized by the French Society of Toxinology on 30 November–1 December 2023
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Pascale Marchot, Ziad Fajloun, Christian Legros, Évelyne Benoit and Sylvie Diochot
Toxins 2024, 16(3), 147; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030147 - 13 Mar 2024
Abstract
The French Society of Toxinology (SFET), which celebrated its 30th anniversary this year, organized its 29th annual Meeting (RT29), shared by 87 participants, on 30 November–1 December 2023. The RT29 main theme, “Toxins: From the Wild to the Lab”, focused on research in
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The French Society of Toxinology (SFET), which celebrated its 30th anniversary this year, organized its 29th annual Meeting (RT29), shared by 87 participants, on 30 November–1 December 2023. The RT29 main theme, “Toxins: From the Wild to the Lab”, focused on research in the field of animal venoms and animal, bacterial, fungal, or plant toxins, from their discovery in nature to their study in the laboratory. The exploration of the functions of toxins, their structures, their molecular or cellular ligands, their mode of action, and their potential therapeutic applications were emphasized during oral communications and posters through three sessions, of which each was dedicated to a secondary theme. A fourth, “miscellaneous” session allowed participants to present recent out-of-theme works. The abstracts of nine invited and 15 selected lectures, those of 24 posters, and the names of the Best Oral Communication and Best Poster awardees, are presented in this report.
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(This article belongs to the Special Issue Toxins: From the Wild to the Lab)
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Open AccessArticle
Bothrops lanceolatus Envenoming in Martinique: A Historical Perspective of the Clinical Effectiveness of Bothrofav Antivenom Treatment
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Dabor Resiere, Jonathan Florentin, Hossein Mehdaoui, Hatem Kallel, Veronique Legris-Allusson, Papa Gueye and Remi Neviere
Toxins 2024, 16(3), 146; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030146 - 13 Mar 2024
Abstract
Bothrofav, a monospecific antivenom, was introduced in June 1991 and has shown excellent effectiveness against life-threatening and thrombotic complications of Bothrops lanceolatus envenoming. Because of the reoccurrence of cerebral stroke events despite the timely administration of antivenom, new batches of Bothrofav were produced
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Bothrofav, a monospecific antivenom, was introduced in June 1991 and has shown excellent effectiveness against life-threatening and thrombotic complications of Bothrops lanceolatus envenoming. Because of the reoccurrence of cerebral stroke events despite the timely administration of antivenom, new batches of Bothrofav were produced and introduced into clinical use in January 2011. This study’s aim was to evaluate the effectiveness of Bothrofav generations at treating B. lanceolatus envenoming. During the first period of the study (2000–2010), 107 patients were treated with vials of antivenom produced in June 1991, while 282 envenomed patients were treated with vials of antivenom produced in January 2011 in the second study period (2011–2023). Despite timely antivenom administration, thrombotic complications reoccurred after an interval free of thrombotic events, and a timeframe analysis suggested that the clinical efficacy of Bothrofav declined after it reached its 10-year shelf-life. In of the case of an antivenom shortage due to the absence of regular batch production, no adverse effects were identified before the antivenom reached its 10-year shelf-life, which is beyond the accepted shelf-life for a liquid-formulation antivenom. While our study does not support the use of expired antivenom for potent, life-threatening B. lanceolatus envenoming, it can be a scientific message to public entities proving the necessity of new antivenom production for B. lanceolatus envenoming.
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(This article belongs to the Special Issue Recent Updates in Venomics and Applications)
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Open AccessArticle
Mutations at Two Key Sites in PP2A Safeguard Caenorhabditis elegans Neurons from Microcystin-LR Toxicity
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Chunhua Zhan and Jianke Gong
Toxins 2024, 16(3), 145; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030145 - 13 Mar 2024
Abstract
Microcystin-LR (MC-LR) is a secondary metabolite produced by cyanobacteria, globally renowned for its potent hepatotoxicity. However, an increasing body of research suggests that it also exhibits pronounced neurotoxicity. PP2A is a fundamental intracellular phosphatase that plays a pivotal role in cell development and
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Microcystin-LR (MC-LR) is a secondary metabolite produced by cyanobacteria, globally renowned for its potent hepatotoxicity. However, an increasing body of research suggests that it also exhibits pronounced neurotoxicity. PP2A is a fundamental intracellular phosphatase that plays a pivotal role in cell development and survival. Although extensive research has focused on the binding of MC-LR to the C subunit of PP2A, few studies have explored the key amino acid sites that can prevent the binding of MC-LR to PP2A-C. Due to the advantages of Caenorhabditis elegans (C. elegans), such as ease of genetic editing and a short lifespan, we exposed nematodes to MC-LR in a manner that simulated natural exposure conditions based on MC-LR concentrations in natural water bodies (immersion exposure). Our findings demonstrate that MC-LR exerts comprehensive toxicity on nematodes, including reducing lifespan, impairing reproductive capabilities, and diminishing sensory functions. Notably, and for the first time, we observed that MC-LR neurotoxic effects can persist up to the F3 generation, highlighting the significant threat that MC-LR poses to biological populations in natural environments. Furthermore, we identified two amino acid sites (L252 and C278) in PP2A-C through mutations that prevented MC-LR binding without affecting PP2A activity. This discovery was robustly validated through behavioral studies and neuronal calcium imaging using nematodes. In conclusion, we identified two crucial amino acid sites that could prevent MC-LR from binding to PP2A-C, which holds great significance for the future development of MC-LR detoxification drugs.
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(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)
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Open AccessArticle
Environmental Toxin Biliatresone-Induced Biliary Atresia-like Abnormal Cilia and Bile Duct Cell Development of Human Liver Organoids
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Yue Hai-Bing, Menon Sudheer Sivasankaran, Babu Rosana Ottakandathil, Wu Zhong-Luan, So Man-Ting, Chung (Patrick) Ho-Yu, Wong (Kenneth) Kak-Yuen, Tam (Paul) Kwong-Hang and Lui (Vincent) Chi-Hang
Toxins 2024, 16(3), 144; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030144 - 11 Mar 2024
Abstract
Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. Biliatresone, a plant toxin, causes BA-like syndrome in some animals, but its relevance in humans is unknown. To validate the hypothesis that biliatresone exposure is a plausible BA
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Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. Biliatresone, a plant toxin, causes BA-like syndrome in some animals, but its relevance in humans is unknown. To validate the hypothesis that biliatresone exposure is a plausible BA disease mechanism in humans, we treated normal human liver organoids with biliatresone and addressed its adverse effects on organoid development, functions and cellular organization. The control organoids (without biliatresone) were well expanded and much bigger than biliatresone-treated organoids. Expression of the cholangiocyte marker CK19 was reduced, while the hepatocyte marker HFN4A was significantly elevated in biliatresone-treated organoids. ZO-1 (a tight junction marker) immunoreactivity was localized at the apical intercellular junctions in control organoids, while it was markedly reduced in biliatresone-treated organoids. Cytoskeleton F-actin was localized at the apical surface of the control organoids, but it was ectopically expressed at the apical and basal sides in biliatresone-treated organoids. Cholangiocytes of control organoids possess primary cilia and elicit cilia mechanosensory function. The number of ciliated cholangiocytes was reduced, and cilia mechanosensory function was hampered in biliatresone-treated organoids. In conclusion, biliatresone induces morphological and developmental changes in human liver organoids resembling those of our previously reported BA organoids, suggesting that environmental toxins could contribute to BA pathogenesis.
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(This article belongs to the Section Plant Toxins)
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Open AccessArticle
New Insights into Interactions between Mushroom Aegerolysins and Membrane Lipids
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Larisa Lara Popošek, Nada Kraševec, Gregor Bajc, Urška Glavač, Matija Hrovatin, Žan Perko, Ana Slavič, Miha Pavšič, Kristina Sepčić and Matej Skočaj
Toxins 2024, 16(3), 143; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030143 - 09 Mar 2024
Abstract
Aegerolysins are a family of proteins that recognize and bind to specific membrane lipids or lipid domains; hence they can be used as membrane lipid sensors. Although aegerolysins are distributed throughout the tree of life, the most studied are those produced by the
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Aegerolysins are a family of proteins that recognize and bind to specific membrane lipids or lipid domains; hence they can be used as membrane lipid sensors. Although aegerolysins are distributed throughout the tree of life, the most studied are those produced by the fungal genus Pleurotus. Most of the aegerolysin-producing mushrooms code also for proteins containing the membrane attack complex/perforin (MACPF)-domain. The combinations of lipid-sensing aegerolysins and MACPF protein partners are lytic for cells harboring the aegerolysin membrane lipid receptor and can be used as ecologically friendly bioinsecticides. In this work, we have recombinantly expressed four novel aegerolysin/MACPF protein pairs from the mushrooms Heterobasidion irregulare, Trametes versicolor, Mucidula mucida, and Lepista nuda, and compared these proteins with the already studied aegerolysin/MACPF protein pair ostreolysin A6–pleurotolysin B from P. ostreatus. We show here that most of these new mushroom proteins can form active aegerolysin/MACPF cytolytic complexes upon aegerolysin binding to membrane sphingolipids. We further disclose that these mushroom aegerolysins bind also to selected glycerophospholipids, in particular to phosphatidic acid and cardiolipin; however, these interactions with glycerophospholipids do not lead to pore formation. Our results indicate that selected mushroom aegerolysins show potential as new molecular biosensors for labelling phosphatidic acid.
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(This article belongs to the Special Issue New Insights into the Diversity, Structure, Function and Evolution of Pore-Forming Toxins)
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Potential Biotechnological Applications of Venoms from the Viperidae Family in Central America for Thrombosis
by
Jorge Eduardo Chang Estrada, Taissa Nunes Guerrero, Daniel Fernando Reyes-Enríquez, Erica Santos Nardy, Roseane Guimarães Ferreira, Cristian José Ruiz Calderón, Irmgardt A. Wellmann, Kaio Murilo Monteiro Espíndola, Alejandro Ferraz do Prado, Andreimar Martins Soares, Marcos Roberto de Mattos Fontes, Marta Chagas Monteiro and Russolina Benedeta Zingali
Toxins 2024, 16(3), 142; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030142 - 08 Mar 2024
Abstract
Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent’s total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the
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Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent’s total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the bite of these animals. A great diversity of biomolecules with immense therapeutic and biotechnological value is contained in their venom. This paper describes the prominent leading representatives of the family Viperidae, emphasizing their morphology, distribution, habitat, feeding, and venom composition, as well as the biotechnological application of some isolated components from the venom of the animals from these families, focusing on molecules with potential anti-thrombotic action. We present the leading protein families that interfere with blood clotting, platelet activity, or the endothelium pro-thrombotic profile. In conclusion, Central America is an endemic region of venomous animals that can provide many molecules for biotechnological applications.
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(This article belongs to the Special Issue Venom Components Acting on the Hemostatic System: Structural and Mechanistic Insights)
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Open AccessArticle
Inhibition of Aflatoxin Production in Aspergillus flavus by a Klebsiella sp. and Its Metabolite Cyclo(l-Ala-Gly)
by
Shohei Sakuda, Masaki Sunaoka, Maho Terada, Ayaka Sakoda, Natsumi Ishijima, Noriko Hakoshima, Kenichi Uchida, Hirofumi Enomoto and Tomohiro Furukawa
Toxins 2024, 16(3), 141; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030141 - 08 Mar 2024
Abstract
During an experiment where we were cultivating aflatoxigenic Aspergillus flavus on peanuts, we accidentally discovered that a bacterium adhering to the peanut strongly inhibited aflatoxin (AF) production by A. flavus. The bacterium, isolated and identified as Klebsiella aerogenes, was found to
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During an experiment where we were cultivating aflatoxigenic Aspergillus flavus on peanuts, we accidentally discovered that a bacterium adhering to the peanut strongly inhibited aflatoxin (AF) production by A. flavus. The bacterium, isolated and identified as Klebsiella aerogenes, was found to produce an AF production inhibitor. Cyclo(l-Ala-Gly), isolated from the bacterial culture supernatant, was the main active component. The aflatoxin production-inhibitory activity of cyclo(l-Ala-Gly) has not been reported. Cyclo(l-Ala-Gly) inhibited AF production in A. flavus without affecting its fungal growth in a liquid medium with stronger potency than cyclo(l-Ala-l-Pro). Cyclo(l-Ala-Gly) has the strongest AF production-inhibitory activity among known AF production-inhibitory diketopiperazines. Related compounds in which the methyl moiety in cyclo(l-Ala-Gly) is replaced by ethyl, propyl, or isopropyl have shown much stronger activity than cyclo(l-Ala-Gly). Cyclo(l-Ala-Gly) did not inhibit recombinant glutathione-S-transferase (GST) in A. flavus, unlike (l-Ala-l-Pro), which showed that the inhibition of GST was not responsible for the AF production-inhibition of cyclo(l-Ala-Gly). When A. flavus was cultured on peanuts dipped for a short period of time in a dilution series bacterial culture broth, AF production in the peanuts was strongly inhibited, even at a 1 × 104-fold dilution. This strong inhibitory activity suggests that the bacterium is a candidate for an effective biocontrol agent for AF control.
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(This article belongs to the Collection Aflatoxins)
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Impact of Botulinum Toxin Injections on Quality of Life of Patients with Long-Standing Peripheral Facial Palsy
by
Jérémy Amar, Frédéric Tankere, Diane Picard, Lauranne Alciato, Fabienne Carré and Claire Foirest
Toxins 2024, 16(3), 140; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030140 - 08 Mar 2024
Abstract
(1) Background: Sequels of facial palsy lead to major psychosocial repercussions, disrupting patients’ quality of life (QoL). Botulinum toxin (BoNT) injections can permit us to treat long-standing facial palsy, improving facial symmetry and functional signs including synkinesis and contractures. (2) Methods: The main
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(1) Background: Sequels of facial palsy lead to major psychosocial repercussions, disrupting patients’ quality of life (QoL). Botulinum toxin (BoNT) injections can permit us to treat long-standing facial palsy, improving facial symmetry and functional signs including synkinesis and contractures. (2) Methods: The main aim of this study was to assess the evolution of the QoL for patients with long-standing facial palsy before, at 1 month, and at 4 months after BoNT injections by using three questionnaires (HFS-30, FaCE, and HAD). The other goals were to find clinical factors associated with the improvement in the QoL and to assess the HFS-30 questionnaire for patients with unilateral facial palsy (3) Results: Eighty-eight patients were included in this study. There was a statistically significant improvement in QoL at 1 month after injections, assessed using the three questionnaires. This improvement was sustained at 4 months after the injections, with a statistically significant difference for the HFS-30 and FaCE questionnaires. (4) Conclusions: This study showed that the BoNT injections lead to a significant increase in the QoL of patients with unilateral facial palsy. This improvement is sustained 4 months after the injections.
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(This article belongs to the Section Bacterial Toxins)
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Human Biomonitoring Guidance Values for Deoxynivalenol Derived under the European Human Biomonitoring Initiative (HBM4EU)
by
Marcel J. B. Mengelers, Annick D. van den Brand, Shensheng Zhao, Rudolf Hoogenveen and Eva Ougier
Toxins 2024, 16(3), 139; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030139 - 07 Mar 2024
Abstract
The mycotoxin deoxynivalenol (DON) was one of the priority substances in the European Joint Human Biomonitoring Initiative (HBM4EU) project. In this study, to better interpret the actual internal exposure of DON in the general population and safeguard public health, human biomonitoring guidance values
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The mycotoxin deoxynivalenol (DON) was one of the priority substances in the European Joint Human Biomonitoring Initiative (HBM4EU) project. In this study, to better interpret the actual internal exposure of DON in the general population and safeguard public health, human biomonitoring guidance values of DON for the general population (HBM-GVGenPop) were derived. The HBM-GVGenPop of DON was based on either the total DON (DON and its glucuronides) or DON’s main metabolite (DON-15-GlcA) levels in 24-h urine samples, resulting in a HBM-GVGenPop of 0.023 µg/mL for the total DON or a HBM-GVGenPop of 0.020 µg/mL for DON-15-GlcA. The use of 24-h urine samples is recommended based on the fact that DON and its metabolites have a short elimination half-life (T1/2), and 95% of the cumulative amount was excreted within 12 h after DON intake. The T1/2 for DON, DON-15-GlcA, and total DON were estimated to be 2.55 h, 2.95 h, and 2.95 h, respectively. Therefore, a 24-h urine sample reflects almost all of the DON exposure from the previous day, and this type of sample was considered for the derivation of a HBM-GVGenPop for DON.
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(This article belongs to the Section Mycotoxins)
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Heterogeneity of Size and Toxin Distribution in Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles
by
Justin B Nice, Shannon M. Collins, Samuel M. J. Agro, Anxhela Sinani, Spencer D. Moros, Leah M. Pasch and Angela C. Brown
Toxins 2024, 16(3), 138; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030138 - 07 Mar 2024
Abstract
Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with localized aggressive periodontitis as well as some systemic diseases. The strains of A. actinomycetemcomitans most closely associated with disease produce more of a secreted leukotoxin (LtxA) than isolates from healthy carriers, suggesting a key role
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Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with localized aggressive periodontitis as well as some systemic diseases. The strains of A. actinomycetemcomitans most closely associated with disease produce more of a secreted leukotoxin (LtxA) than isolates from healthy carriers, suggesting a key role for this toxin in disease progression. LtxA is released into the bacterial cytosol in a free form as well as in association with the surface of outer membrane vesicles (OMVs). We previously observed that the highly leukotoxic A. actinomycetemcomitans strain JP2 produces two populations of OMVs: a highly abundant population of small (<100 nm) OMVs and a less abundant population of large (>300 nm) OMVs. Here, we have developed a protocol to isolate the OMVs produced during each specific phase of growth and used this to demonstrate that small OMVs are produced throughout growth and lack LtxA, while large OMVs are produced only during the exponential phase and are enriched with LtxA. Our results indicate that surface-associated DNA drives the selective sorting of LtxA into large OMVs. This study provides valuable insights into the observed heterogeneity of A. actinomycetemcomitans vesicles and emphasizes the importance of understanding these variations in the context of bacterial pathogenesis.
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(This article belongs to the Section Bacterial Toxins)
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Toxins 2024, 16(3), 147; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins16030147
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