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
Indoxyl Sulfate-Induced Macrophage Toxicity and Therapeutic Strategies in Uremic Atherosclerosis
Toxins 2024, 16(6), 254; https://doi.org/10.3390/toxins16060254 (registering DOI) - 31 May 2024
Abstract
Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be related to traditional risk factors and CKD-specific factors that accelerate atherosclerosis and vascular calcification in CKD patients. The accumulation of uremic
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Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be related to traditional risk factors and CKD-specific factors that accelerate atherosclerosis and vascular calcification in CKD patients. The accumulation of uremic toxins is a significant factor in CKD-related systemic disorders. Basic research suggests that indoxyl sulfate (IS), a small protein-bound uremic toxin, is associated with macrophage dysfunctions, including increased oxidative stress, exacerbation of chronic inflammation, and abnormalities in lipid metabolism. Strategies to mitigate the toxicity of IS include optimizing gut microbiota, intervening against the abnormality of intracellular signal transduction, and using blood purification therapy with higher efficiency. Further research is needed to examine whether lowering protein-bound uremic toxins through intervention leads to a reduction in CVD in patients with CKD.
Full article
(This article belongs to the Special Issue Uremic Toxins Lowering Strategies in Chronic Kidney Disease)
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Open AccessArticle
Actinobacteria as Promising Biocontrol Agents for In Vitro and In Planta Degradation and Detoxification of Zearalenone
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Larissa De Troyer, Noémie De Zutter, Sarah De Saeger, Frédéric Dumoulin, Siska Croubels, Siegrid De Baere, Leen De Gelder and Kris Audenaert
Toxins 2024, 16(6), 253; https://doi.org/10.3390/toxins16060253 - 28 May 2024
Abstract
Zearalenone (ZEN) is a prevalent mycotoxin found in grains and grain-derived products, inducing adverse health effects in both animals and humans. The in-field application of microorganisms to degrade and detoxify ZEN is a promising strategy to enhance the safety of food and feed.
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Zearalenone (ZEN) is a prevalent mycotoxin found in grains and grain-derived products, inducing adverse health effects in both animals and humans. The in-field application of microorganisms to degrade and detoxify ZEN is a promising strategy to enhance the safety of food and feed. In this study, we investigated the potential of three actinobacterial strains to degrade and detoxify ZEN in vitro and in planta on wheat ears. The residual ZEN concentration and toxicity in the samples were analysed with UHPLC-MS/MS and a bioluminescence BLYES assay, respectively. Streptomyces rimosus subsp. rimosus LMG19352 could completely degrade and detoxify 5 mg/L ZEN in LB broth within 24 h, along with significant reductions in ZEN concentration both in a minimal medium (MM) and on wheat ears. Additionally, it was the only strain that showed a significant colonisation of these ears. Rhodococcus sp. R25614 exhibited partial but significant degradation in LB broth and MM, whereas Streptomyces sp. LMG16995 degraded and detoxified ZEN in LB broth after 72 h by 39% and 33%, respectively. Although all three actinobacterial strains demonstrated the metabolic capability to degrade and detoxify ZEN in vitro, only S. rimosus subsp. rimosus LMG19352 showed promising potential to mitigate ZEN in planta. This distinction underscores the importance of incorporating in planta screening assays for assessing the potential of mycotoxin-biotransforming microorganisms as biocontrol agents.
Full article
(This article belongs to the Special Issue Mitigation and Detoxification Strategies of Mycotoxins)
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Open AccessArticle
Concomitant Botulinum Toxin Injections for Neurogenic Detrusor Overactivity and Spasticity—A Retrospective Analysis of Practice and Safety
by
Arnaud Leilaz, Charles Joussain, Pierre Denys, Djamel Bensmail and Jonathan Levy
Toxins 2024, 16(6), 252; https://doi.org/10.3390/toxins16060252 - 28 May 2024
Abstract
As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis
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As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017–2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1–14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.
Full article
(This article belongs to the Special Issue Botulinum Neurotoxin as Novel Therapy of Spasticity and Disorder Movement)
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Open AccessArticle
Frequent Dietary Multi-Mycotoxin Exposure in UK Children and Its Association with Dietary Intake
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Praosiri Charusalaipong, Margaret-Jane Gordon, Louise Cantlay, Nicosha De Souza, Graham W. Horgan, Ruth Bates and Silvia W. Gratz
Toxins 2024, 16(6), 251; https://doi.org/10.3390/toxins16060251 - 28 May 2024
Abstract
Mycotoxins are potent fungal toxins that frequently contaminate agricultural crops and foods. Mycotoxin exposure is frequently reported in humans, and children are known to be particularly at risk of exceeding safe levels of exposure. Urinary biomonitoring is used to assess overall dietary exposure
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Mycotoxins are potent fungal toxins that frequently contaminate agricultural crops and foods. Mycotoxin exposure is frequently reported in humans, and children are known to be particularly at risk of exceeding safe levels of exposure. Urinary biomonitoring is used to assess overall dietary exposure to multiple mycotoxins. This study aims to quantify multi-mycotoxin exposure in UK children and to identify major food groups contributing to exposure. Four repeat urine samples were collected from 29 children (13 boys and 16 girls, aged 2.4–6.8 years), and food diaries were recorded to assess their exposure to eleven mycotoxins. Urine samples (n = 114) were hydrolysed with β-glucuronidase, enriched through immunoaffinity columns and analysed by LC-MS/MS for deoxynivalenol (DON), nivalenol (NIV), T-2/HT-2 toxins, zearalenone (ZEN), ochratoxin A (OTA) and aflatoxins. Food diaries were analysed using WinDiet software, and the daily intake of high-risk foods for mycotoxin contamination summarised. The most prevalent mycotoxins found in urine samples were DON (95.6% of all samples), OTA (88.6%), HT-2 toxin (53.5%), ZEN (48.2%) and NIV (26.3%). Intake of total cereal-based foods was strongly positively associated with urinary levels of DON and T-2/HT-2 and oat intake with urinary T-2/HT-2. Average daily mycotoxin excretion ranged from 12.10 µg/d (DON) to 0.03 µg/d (OTA), and co-exposure to three or more mycotoxins was found in 66% of samples. Comparing mycotoxin intake estimates to tolerable daily intakes (TDI) demonstrates frequent TDI exceedances (DON 34.2% of all samples, T-2/HT-2 14.9%, NIV 4.4% and ZEN 5.2%). OTA was frequently detected at low levels. When mean daily OTA intake was compared to the reference value for non-neoplastic lesions, the resulting Margin of Exposure (MoE) of 65 was narrow, indicating a health concern. In conclusion, this study demonstrates frequent exposure of UK children to multiple mycotoxins at levels high enough to pose a health concern if exposure is continuous.
Full article
(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)
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Open AccessCorrection
Correction: de Oliveira et al. Viper Venom Phospholipase A2 Database: The Structural and Functional Anatomy of a Primary Toxin in Envenomation. Toxins 2024, 16, 71
by
Ana L. Novo de Oliveira, Miguel T. Lacerda, Maria J. Ramos and Pedro A. Fernandes
Toxins 2024, 16(6), 250; https://doi.org/10.3390/toxins16060250 - 28 May 2024
Abstract
In the published publication [...]
Full article
Open AccessReview
Application of Biosensors for the Detection of Mycotoxins for the Improvement of Food Safety
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Rafał Szelenberger, Natalia Cichoń, Wojciech Zajaczkowski and Michal Bijak
Toxins 2024, 16(6), 249; https://doi.org/10.3390/toxins16060249 - 27 May 2024
Abstract
Mycotoxins, secondary metabolites synthesized by various filamentous fungi genera such as Aspergillus, Penicillium, Fusarium, Claviceps, and Alternaria, are potent toxic compounds. Their production is contingent upon specific environmental conditions during fungal growth. Arising as byproducts of fungal metabolic
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Mycotoxins, secondary metabolites synthesized by various filamentous fungi genera such as Aspergillus, Penicillium, Fusarium, Claviceps, and Alternaria, are potent toxic compounds. Their production is contingent upon specific environmental conditions during fungal growth. Arising as byproducts of fungal metabolic processes, mycotoxins exhibit significant toxicity, posing risks of acute or chronic health complications. Recognized as highly hazardous food contaminants, mycotoxins present a pervasive threat throughout the agricultural and food processing continuum, from plant cultivation to post-harvest stages. The imperative to adhere to principles of good agricultural and industrial practice is underscored to mitigate the risk of mycotoxin contamination in food production. In the domain of food safety, the rapid and efficient detection of mycotoxins holds paramount significance. This paper delineates conventional and commercial methodologies for mycotoxin detection in ensuring food safety, encompassing techniques like liquid chromatography, immunoassays, and test strips, with a significant emphasis on the role of electrochemiluminescence (ECL) biosensors, which are known for their high sensitivity and specificity. These are categorized into antibody-, and aptamer-based, as well as molecular imprinting methods. This paper examines the latest advancements in biosensors for mycotoxin testing, with a particular focus on their amplification strategies and operating mechanisms.
Full article
(This article belongs to the Special Issue Mycotoxins in Food: Detection, Contamination and Management Strategies)
Open AccessArticle
α-Latrotoxin Tetramers Spontaneously Form Two-Dimensional Crystals in Solution and Coordinated Multi-Pore Assemblies in Biological Membranes
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Alexis Rohou, Edward P. Morris, Julia Makarova, Alexander G. Tonevitsky and Yuri A. Ushkaryov
Toxins 2024, 16(6), 248; https://doi.org/10.3390/toxins16060248 - 27 May 2024
Abstract
α-Latrotoxin (α-LTX) was found to form two-dimensional (2D) monolayer arrays in solution at relatively low concentrations (0.1 mg/mL), with the toxin tetramer constituting a unit cell. The crystals were imaged using cryogenic electron microscopy (cryoEM), and image analysis yielded a ~12 Å projection
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α-Latrotoxin (α-LTX) was found to form two-dimensional (2D) monolayer arrays in solution at relatively low concentrations (0.1 mg/mL), with the toxin tetramer constituting a unit cell. The crystals were imaged using cryogenic electron microscopy (cryoEM), and image analysis yielded a ~12 Å projection map. At this resolution, no major conformational changes between the crystalline and solution states of α-LTX tetramers were observed. Electrophysiological studies showed that, under the conditions of crystallization, α-LTX simultaneously formed multiple channels in biological membranes that displayed coordinated gating. Two types of channels with conductance levels of 120 and 208 pS were identified. Furthermore, we observed two distinct tetramer conformations of tetramers both when observed as monodisperse single particles and within the 2D crystals, with pore diameters of 11 and 13.5 Å, suggestive of a flickering pore in the middle of the tetramer, which may correspond to the two states of toxin channels with different conductance levels. We discuss the structural changes that occur in α-LTX tetramers in solution and propose a mechanism of α-LTX insertion into the membrane. The propensity of α-LTX tetramers to form 2D crystals may explain many features of α-LTX toxicology and suggest that other pore-forming toxins may also form arrays of channels to exert maximal toxic effect.
Full article
(This article belongs to the Special Issue New Aspects in Clinical Characteristics and Toxicology of Animal Venom)
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Open AccessArticle
Effects of Scallop Mantle Toxin on Intestinal Microflora and Intestinal Barrier Function in Mice
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Xiong Geng, Ran Lin, Yasushi Hasegawa, Luomeng Chao, Huayan Shang, Jingjing Yang, Weina Tian, Wenting Ma, Miaomiao Zhuang and Jianrong Li
Toxins 2024, 16(6), 247; https://doi.org/10.3390/toxins16060247 - 27 May 2024
Abstract
Previous studies have shown that feeding mice with food containing mantle tissue from Japanese scallops results in aggravated liver and kidney damage, ultimately resulting in mortality within weeks. The aim of this study is to evaluate the toxicity of scallop mantle in China’s
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Previous studies have shown that feeding mice with food containing mantle tissue from Japanese scallops results in aggravated liver and kidney damage, ultimately resulting in mortality within weeks. The aim of this study is to evaluate the toxicity of scallop mantle in China’s coastal areas and explore the impact of scallop mantle toxins (SMT) on intestinal barrier integrity and gut microbiota in mice. The Illumina MiSeq sequencing of V3-V4 hypervariable regions of 16S ribosomal RNA was employed to study the alterations in gut microbiota in the feces of SMT mice. The results showed that intestinal flora abundance and diversity in the SMT group were decreased. Compared with the control group, significant increases were observed in serum indexes related to liver, intestine, inflammation, and kidney functions among SMT-exposed mice. Accompanied by varying degrees of tissue damage observed within these organs, the beneficial bacteria of Muribaculaceae and Marinifilaceae significantly reduced, while the harmful bacteria of Enterobacteriaceae and Helicobacter were significantly increased. Taken together, this article elucidates the inflammation and glucose metabolism disorder caused by scallop mantle toxin in mice from the angle of gut microbiota and metabolism. SMT can destroy the equilibrium of intestinal flora and damage the intestinal mucosal barrier, which leads to glucose metabolism disorder and intestinal dysfunction and may ultimately bring about systemic toxicity.
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(This article belongs to the Section Marine and Freshwater Toxins)
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Open AccessArticle
Retrospective Evaluation of Clinical and Clinicopathologic Findings, Case Management, and Outcome for Dogs and Cats Exposed to Micrurus fulvius (Eastern Coral Snake): 92 Cases (2021–2022)
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Jordan M. Sullivan, Taelor L. Aasen, Corey J. Fisher and Michael Schaer
Toxins 2024, 16(6), 246; https://doi.org/10.3390/toxins16060246 - 27 May 2024
Abstract
This retrospective, observational study describes the clinical findings, case management trends, and outcomes of 83 dogs and nine cats exposed to eastern coral snakes in a university teaching hospital setting. The medical records of dogs and cats that received antivenom following coral snake
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This retrospective, observational study describes the clinical findings, case management trends, and outcomes of 83 dogs and nine cats exposed to eastern coral snakes in a university teaching hospital setting. The medical records of dogs and cats that received antivenom following coral snake exposure were reviewed. Data collected included signalment, time to antivenom administration, physical and laboratory characteristics at presentation, clinical course during hospitalization, length of hospitalization, and survival to discharge. The mean time from presentation to coral snake antivenom administration was 2.26 ± 1.46 h. Excluding cases where the owner declined in-hospital care, the mean hospitalization time for dogs and cats was 50.8 h and 34 h, respectively. The mean number of antivenom vials was 1.29 (1–4). Gastrointestinal signs (vomiting and ptyalism) occurred in 42.2% (35/83) of dogs and 33.3% (3/9) of cats. Peripheral neurologic system deficits (ataxia, paresis to plegia, absent reflexes, and hypoventilation) were noted in 19.6% (18/92) of dogs and cats. Hemolysis was also common in 37.9% (25/66) of dogs but was not observed in cats. Mechanical ventilation (MV) was indicated in 12% (10/83) of dogs but no cats. Acute kidney injury (AKI), while rare, was a common cause of euthanasia at 20% (2/5) and was the most common complication during MV at 44.4% (4/9). Pigmenturia/hemolysis occurred in 88.9% (8/9) of MV cases and in all cases with AKI. Despite delays in antivenom administration by several hours, dogs and cats with coral snake exposure have low mortality rates (6% of dogs (5/83) and 0% of cats). Gastrointestinal signs were common but were not predictive of progression to neurological signs. Thus, differentiating between coral snake exposure and envenomation before the onset of neurological signs remains challenging.
Full article
(This article belongs to the Special Issue Pre-clinical and Clinical Management of Snakebite Envenomation)
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Challenges of Diphtheria Toxin Detection
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Marta Prygiel, Ewa Mosiej, Maciej Polak, Katarzyna Krysztopa-Grzybowska, Karol Wdowiak, Kamila Formińska and Aleksandra A. Zasada
Toxins 2024, 16(6), 245; https://doi.org/10.3390/toxins16060245 - 26 May 2024
Abstract
Diphtheria toxin (DT) is the main virulence factor of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Moreover, new Corynebacterium species with the potential to produce diphtheria toxin have also been described. Therefore, the detection of the toxin is the most important test in
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Diphtheria toxin (DT) is the main virulence factor of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Moreover, new Corynebacterium species with the potential to produce diphtheria toxin have also been described. Therefore, the detection of the toxin is the most important test in the microbiological diagnosis of diphtheria and other corynebacteria infections. Since the first demonstration in 1888 that DT is a major virulence factor of C. diphtheriae, responsible for the systemic manifestation of the disease, various methods for DT detection have been developed, but the diagnostic usefulness of most of them has not been confirmed on a sufficiently large group of samples. Despite substantial progress in the science and diagnostics of infectious diseases, the Elek test is still the basic recommended diagnostic test for DT detection. The challenge here is the poor availability of an antitoxin and declining experience even in reference laboratories due to the low prevalence of diphtheria in developed countries. However, recent and very promising assays have been developed with the potential for use as rapid point-of-care testing (POCT), such as ICS and LFIA for toxin detection, LAMP for tox gene detection, and biosensors for both.
Full article
(This article belongs to the Special Issue Multi Methods for Detecting Natural Toxins)
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Open AccessReview
Progress on Electrochemical Biomimetic Nanosensors for the Detection and Monitoring of Mycotoxins and Pesticides
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Kavitha Lakavath, Chandan Kafley, Anjana Sajeevan, Soumyajit Jana, Jean Louis Marty and Yugender Goud Kotagiri
Toxins 2024, 16(6), 244; https://doi.org/10.3390/toxins16060244 - 26 May 2024
Abstract
Monitoring agricultural toxins such as mycotoxins is crucial for a healthy society. High concentrations of these toxins lead to the cause of several chronic diseases; therefore, developing analytical systems for detecting/monitoring agricultural toxins is essential. These toxins are found in crops such as
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Monitoring agricultural toxins such as mycotoxins is crucial for a healthy society. High concentrations of these toxins lead to the cause of several chronic diseases; therefore, developing analytical systems for detecting/monitoring agricultural toxins is essential. These toxins are found in crops such as vegetables, fruits, food, and beverage products. Currently, screening of these toxins is mostly performed with sophisticated instrumentation such as chromatography and spectroscopy techniques. However, these techniques are very expensive and require extensive maintenance, and their availability is limited to metro cities only. Alternatively, electrochemical biomimetic sensing methodologies have progressed hugely during the last decade due to their unique advantages like point-of-care sensing, miniaturized instrumentations, and mobile/personalized monitoring systems. Specifically, affinity-based sensing strategies including immunosensors, aptasensors, and molecular imprinted polymers offer tremendous sensitivity, selectivity, and stability to the sensing system. The current review discusses the principal mechanisms and the recent developments in affinity-based sensing methodologies for the detection and continuous monitoring of mycotoxins and pesticides. The core discussion has mainly focused on the fabrication protocols, advantages, and disadvantages of affinity-based sensing systems and different exploited electrochemical transduction techniques.
Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Rapid Mycotoxin Testing)
Open AccessArticle
Glycan Profile and Sequence Variants of Certified Ricin Reference Material and Other Ricin Samples Yield Unique Molecular Signature Features
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Roland Josuran, Andreas Wenger, Christian Müller, Bettina Kampa, Sylvia Worbs, Brigitte G. Dorner and Sabina Gerber
Toxins 2024, 16(6), 243; https://doi.org/10.3390/toxins16060243 - 26 May 2024
Abstract
A certified reference material of ricin (CRM-LS-1) was produced by the EuroBioTox consortium to standardise the analysis of this biotoxin. This study established the N-glycan structures and proportions including their loci and occupancy of ricin CRM-LS-1. The glycan profile was compared with
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A certified reference material of ricin (CRM-LS-1) was produced by the EuroBioTox consortium to standardise the analysis of this biotoxin. This study established the N-glycan structures and proportions including their loci and occupancy of ricin CRM-LS-1. The glycan profile was compared with ricin from different preparations and other cultivars and isoforms. A total of 15 different oligomannosidic or paucimannosidic structures were identified in CRM-LS-1. Paucimannose was mainly found within the A-chain and oligomannose constituted the major glycan type of the B-chain. Furthermore, the novel primary structure variants E138 and D138 and four different C-termini of the A-chain as well as two B-chain variants V250 and F250 were elucidated. While the glycan proportions and loci were similar among all variants in CRM-LS-1 and ricin isoforms D and E of all cultivars analysed, a different stoichiometry for isoforms D and E and the amino acid variants were found. This detailed physicochemical characterization of ricin regarding the glycan profile and amino acid sequence variations yields unprecedented insight into the molecular features of this protein toxin. The variable attributes discovered within different cultivars present signature motifs and may allow discrimination of the biotoxin’s origin that are important in molecular forensic profiling. In conclusion, our data of in-depth CRM-LS-1 characterization combined with the analysis of other cultivars is representative for known ricin variants.
Full article
(This article belongs to the Special Issue The EuroBioTox Project: Progress Towards the Detection and Identification of Biotoxins via Standardization, Training, and Method Evaluation)
Open AccessReview
Revitalizing the Gut Microbiome in Chronic Kidney Disease: A Comprehensive Exploration of the Therapeutic Potential of Physical Activity
by
Marieke Vandecruys, Stefan De Smet, Jasmine De Beir, Marie Renier, Sofie Leunis, Hanne Van Criekinge, Griet Glorieux, Jeroen Raes, Karsten Vanden Wyngaert, Evi Nagler, Patrick Calders, Diethard Monbaliu, Véronique Cornelissen, Pieter Evenepoel and Amaryllis H. Van Craenenbroeck
Toxins 2024, 16(6), 242; https://doi.org/10.3390/toxins16060242 - 26 May 2024
Abstract
Both physical inactivity and disruptions in the gut microbiome appear to be prevalent in patients with chronic kidney disease (CKD). Engaging in physical activity could present a novel nonpharmacological strategy for enhancing the gut microbiome and mitigating the adverse effects associated with microbial
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Both physical inactivity and disruptions in the gut microbiome appear to be prevalent in patients with chronic kidney disease (CKD). Engaging in physical activity could present a novel nonpharmacological strategy for enhancing the gut microbiome and mitigating the adverse effects associated with microbial dysbiosis in individuals with CKD. This narrative review explores the underlying mechanisms through which physical activity may favorably modulate microbial health, either through direct impact on the gut or through interorgan crosstalk. Also, the development of microbial dysbiosis and its interplay with physical inactivity in patients with CKD are discussed. Mechanisms and interventions through which physical activity may restore gut homeostasis in individuals with CKD are explored.
Full article
(This article belongs to the Special Issue Toxins: 15th Anniversary)
Open AccessReview
Clostridioides difficile Toxins: Host Cell Interactions and Their Role in Disease Pathogenesis
by
Md Zahidul Alam and Rajat Madan
Toxins 2024, 16(6), 241; https://doi.org/10.3390/toxins16060241 - 24 May 2024
Abstract
Clostridioides difficile, a Gram-positive anaerobic bacterium, is the leading cause of hospital-acquired antibiotic-associated diarrhea worldwide. The severity of C. difficile infection (CDI) varies, ranging from mild diarrhea to life-threatening conditions such as pseudomembranous colitis and toxic megacolon. Central to the pathogenesis of
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Clostridioides difficile, a Gram-positive anaerobic bacterium, is the leading cause of hospital-acquired antibiotic-associated diarrhea worldwide. The severity of C. difficile infection (CDI) varies, ranging from mild diarrhea to life-threatening conditions such as pseudomembranous colitis and toxic megacolon. Central to the pathogenesis of the infection are toxins produced by C. difficile, with toxin A (TcdA) and toxin B (TcdB) as the main virulence factors. Additionally, some strains produce a third toxin known as C. difficile transferase (CDT). Toxins damage the colonic epithelium, initiating a cascade of cellular events that lead to inflammation, fluid secretion, and further tissue damage within the colon. Mechanistically, the toxins bind to cell surface receptors, internalize, and then inactivate GTPase proteins, disrupting the organization of the cytoskeleton and affecting various Rho-dependent cellular processes. This results in a loss of epithelial barrier functions and the induction of cell death. The third toxin, CDT, however, functions as a binary actin-ADP-ribosylating toxin, causing actin depolymerization and inducing the formation of microtubule-based protrusions. In this review, we summarize our current understanding of the interaction between C. difficile toxins and host cells, elucidating the functional consequences of their actions. Furthermore, we will outline how this knowledge forms the basis for developing innovative, toxin-based strategies for treating and preventing CDI.
Full article
(This article belongs to the Special Issue Intracellular Transport of Toxins: Insights into Mechanisms of Cytotoxicity and Applications in Cell Biology and Medicine)
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Open AccessArticle
Identification and Evolutionary Analysis of the Widely Distributed CAP Superfamily in Spider Venom
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Hongcen Jiang, Yiru Wang, Guoqing Zhang, Anqiang Jia, Zhaoyuan Wei and Yi Wang
Toxins 2024, 16(6), 240; https://doi.org/10.3390/toxins16060240 - 24 May 2024
Abstract
Venom plays a crucial role in the defense and predation of venomous animals. Spiders (Araneae) are among the most successful predators and have a fascinating venom composition. Their venom mainly contains disulfide-rich peptides and large proteins. Here, we analyzed spider venom protein families,
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Venom plays a crucial role in the defense and predation of venomous animals. Spiders (Araneae) are among the most successful predators and have a fascinating venom composition. Their venom mainly contains disulfide-rich peptides and large proteins. Here, we analyzed spider venom protein families, utilizing transcriptomic and genomic data, and highlighted their similarities and differences. We show that spiders have specific combinations of toxins for better predation and defense, typically comprising a core toxin expressed alongside several auxiliary toxins. Among them, the CAP superfamily is widely distributed and highly expressed in web-building Araneoidea spiders. Our analysis of evolutionary relationships revealed four subfamilies (subA-subD) of the CAP superfamily that differ in structure and potential functions. CAP proteins are composed of a conserved CAP domain and diverse C-terminal domains. CAP subC shares similar domains with the snake ion channel regulator svCRISP proteins, while CAP subD possesses a sequence similar to that of insect venom allergen 5 (Ag5). Furthermore, we show that gene duplication and selective expression lead to increased expression of CAP subD, making it a core member of the CAP superfamily. This study sheds light on the functional diversity of CAP subfamilies and their evolutionary history, which has important implications for fully understanding the composition of spider venom proteins and the core toxin components of web-building spiders.
Full article
(This article belongs to the Special Issue Transcriptomic and Proteomic Study on Animal Venom: Looking Forward)
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Open AccessArticle
The Effects of Aflatoxin B1 on Liver Cholestasis and Its Nutritional Regulation in Ducks
by
Aimei Yu, Huanbin Wang, Qianhui Cheng, Shahid Ali Rajput and Desheng Qi
Toxins 2024, 16(6), 239; https://doi.org/10.3390/toxins16060239 - 24 May 2024
Abstract
The aim of this study was to investigate the effects of aflatoxin B1 (AFB1) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old ducks were randomly divided into six groups and fed for 4 weeks. The
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The aim of this study was to investigate the effects of aflatoxin B1 (AFB1) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old ducks were randomly divided into six groups and fed for 4 weeks. The control group was fed a basic diet, while the experimental group diet contained 90 μg/kg of AFB1. Cholestyramine, atorvastatin calcium, taurine, and emodin were added to the diets of four experimental groups. The results show that in the AFB1 group, the growth properties, total bile acid (TBA) serum levels and total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) liver levels decreased, while the malondialdehyde (MDA) and TBA liver levels increased (p < 0.05). Moreover, AFB1 caused cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin could reduce the TBA serum and liver levels (p < 0.05), alleviating the symptoms of cholestasis. The qPCR results show that AFB1 upregulated cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) gene expression and downregulated ATP binding cassette subfamily B member 11 (BSEP) gene expression in the liver, and taurine and emodin downregulated CYP7A1 and CYP8B1 gene expression (p < 0.05). In summary, AFB1 negatively affects health and alters the expression of genes related to liver bile acid metabolism, leading to cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin can alleviate AFB1-induced cholestasis.
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(This article belongs to the Special Issue Aspergillus flavus and Aflatoxins (Volume III))
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Determination of Patulin in Apple Juice and Apple-Derived Products Using a Robotic Sample Preparation System and LC-APCI-MS/MS
by
Kai Zhang and Lauren Zhang
Toxins 2024, 16(6), 238; https://doi.org/10.3390/toxins16060238 - 23 May 2024
Abstract
Patulin, a toxic mycotoxin, can contaminate apple-derived products. The FDA has established an action level of 50 ppb (ng/g) for patulin in apple juice and apple juice products. To effectively monitor this mycotoxin, there is a need for adequate analytical methods that can
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Patulin, a toxic mycotoxin, can contaminate apple-derived products. The FDA has established an action level of 50 ppb (ng/g) for patulin in apple juice and apple juice products. To effectively monitor this mycotoxin, there is a need for adequate analytical methods that can reliably and efficiently determine patulin levels. In this work, we developed an automated sample preparation workflow followed by liquid chromatography–atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) detection to identify and quantify patulin in a single method, further expanding testing capabilities for monitoring patulin in foods compared to traditional optical methods. Using a robotic sample preparation system, apple juice, apple cider, apple puree, apple-based baby food, applesauce, fruit rolls, and fruit jam were fortified with 13C-patulin and extracted using dichloromethane (DCM) without human intervention, followed by an LC-APCI-MS/MS analysis in negative ionization mode. The method achieved a limit of quantification of 4.0 ng/g and linearity ranging from 2 to 1000 ng/mL (r2 > 0.99). Quantitation was performed with isotope dilution using 13C-patulin as an internal standard and solvent calibration standards. Average recoveries (relative standard deviations, RSD%) in seven spike matrices were 95% (9%) at 10 ng/g, 110% (5%) at 50 ng/g, 101% (7%) at 200 ng/g, and 104% (4%) at 1000 ng/g (n = 28). The ranges of within-matrix and between-matrix variability (RSD) were 3–8% and 4–9%, respectively. In incurred samples, the identity of patulin was further confirmed with a comparison of the information-dependent acquisition-enhanced product ion (IDA-EPI) MS/MS spectra to a reference standard. The metrological traceability of the patulin measurements in an incurred apple cider (21.1 ± 8.0 µg/g) and apple juice concentrate (56.6 ± 15.6 µg/g) was established using a certified reference material and calibration data to demonstrate data confidence intervals (k = 2, 95% confidence interval).
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(This article belongs to the Section Mycotoxins)
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Sensitive Detection and Differentiation of Biologically Active Ricin and Abrin in Complex Matrices via Specific Neutralizing Antibody-Based Cytotoxicity Assay
by
Zhi Li, Bo Ma, Mengqiang Gong, Lei Guo, Lili Wang, Hua Xu and Jianwei Xie
Toxins 2024, 16(6), 237; https://doi.org/10.3390/toxins16060237 - 23 May 2024
Abstract
Ricin and abrin are highly potent plant-derived toxins, categorized as type II ribosome-inactivating proteins. High toxicity, accessibility, and the lack of effective countermeasures make them potential agents in bioterrorism and biowarfare, posing significant threats to public safety. Despite the existence of many effective
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Ricin and abrin are highly potent plant-derived toxins, categorized as type II ribosome-inactivating proteins. High toxicity, accessibility, and the lack of effective countermeasures make them potential agents in bioterrorism and biowarfare, posing significant threats to public safety. Despite the existence of many effective analytical strategies for detecting these two lethal toxins, current methods are often hindered by limitations such as insufficient sensitivity, complex sample preparation, and most importantly, the inability to distinguish between biologically active and inactive toxin. In this study, a cytotoxicity assay was developed to detect active ricin and abrin based on their potent cell-killing capability. Among nine human cell lines derived from various organs, HeLa cells exhibited exceptional sensitivity, with limits of detection reaching 0.3 ng/mL and 0.03 ng/mL for ricin and abrin, respectively. Subsequently, toxin-specific neutralizing monoclonal antibodies MIL50 and 10D8 were used to facilitate the precise identification and differentiation of ricin and abrin. The method provides straightforward and sensitive detection in complex matrices including milk, plasma, coffee, orange juice, and tea via a simple serial-dilution procedure without any complex purification and enrichment steps. Furthermore, this assay was successfully applied in the unambiguous identification of active ricin and abrin in samples from OPCW biotoxin exercises.
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(This article belongs to the Special Issue Multi Methods for Detecting Natural Toxins)
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The Possible Role of Mycotoxins in the Pathogenesis of Endometrial Cancer
by
Márkó Unicsovics, Zsófia Molnár, Miklós Mézes, Katalin Posta, György Nagyéri, Szabolcs Várbíró, Nándor Ács, Levente Sára and Zsuzsanna Szőke
Toxins 2024, 16(6), 236; https://doi.org/10.3390/toxins16060236 - 23 May 2024
Abstract
Endometrial cancer is one of the most common cancer types among women. Many factors can contribute to the development of this disease, including environmental factors and, thus, eating habits. Our study aims to determine the levels of various mycotoxins and their metabolites in
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Endometrial cancer is one of the most common cancer types among women. Many factors can contribute to the development of this disease, including environmental factors and, thus, eating habits. Our study aims to determine the levels of various mycotoxins and their metabolites in the blood serum and endometrial tissue samples of participants with previously proven endometrial cancer and to find possible contributions to cancer development. In the cohort clinical trial, 52 participants aged between 44 and 86 were studied. The participants were divided into two groups: patients or matched controls. All patients had previously histologically diagnosed endometrial cancer. The cancer patients were divided into low-grade endometrioid and low- plus high-grade endometrioid groups. Controls had no history of endometrial malignancy or premalignancy. Blood serum and endometrial tissue samples were obtained from all study patients. We compared the concentrations of total Aflatoxins (Afs), Deoxynivalenol (DON), Ochratoxin-A (OTA), T2-toxin and HT2 toxin (T2/HT2 toxin), Zearalenone (ZEN), alpha-Zearalenol (α-ZOL), and Fumonisin B1 (FB1) in the serum and endometrium between the different study groups. As a result, we can see a significant correlation between the higher levels of Afs and zearalenone and the presence of endometrial cancer. In the case of Afs, DON, OTA, T2/HT2 toxins, ZEN, and alpha-ZOL, we measured higher endometrial concentrations than in serum. Considering the effect of mycotoxins and eating habits on cancer development, our results might lead to further research exploring the relationship between certain mycotoxins and endometrium cancer.
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(This article belongs to the Special Issue Advances in Contamination, Detection and Risk Assessment of Mycotoxins)
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Mechanism of Fumonisin Self-Resistance: Fusarium verticillioides Contains Four Fumonisin B1-Insensitive-Ceramide Synthases
by
Tamara Krska, Krisztian Twaruschek, Gerlinde Wiesenberger, Franz Berthiller and Gerhard Adam
Toxins 2024, 16(6), 235; https://doi.org/10.3390/toxins16060235 - 22 May 2024
Abstract
Fusarium verticillioides produces fumonisins, which are mycotoxins inhibiting sphingolipid biosynthesis in humans, animals, and other eukaryotes. Fumonisins are presumed virulence factors of plant pathogens, but may also play a role in interactions between competing fungi. We observed higher resistance to added fumonisin B
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Fusarium verticillioides produces fumonisins, which are mycotoxins inhibiting sphingolipid biosynthesis in humans, animals, and other eukaryotes. Fumonisins are presumed virulence factors of plant pathogens, but may also play a role in interactions between competing fungi. We observed higher resistance to added fumonisin B1 (FB1) in fumonisin-producing Fusarium verticillioides than in nonproducing F. graminearum, and likewise between isolates of Aspergillus and Alternaria differing in production of sphinganine-analog toxins. It has been reported that in F. verticillioides, ceramide synthase encoded in the fumonisin biosynthetic gene cluster is responsible for self-resistance. We reinvestigated the role of FUM17 and FUM18 by generating a double mutant strain in a fum1 background. Nearly unchanged resistance to added FB1 was observed compared to the parental fum1 strain. A recently developed fumonisin-sensitive baker’s yeast strain allowed for the testing of candidate ceramide synthases by heterologous expression. The overexpression of the yeast LAC1 gene, but not LAG1, increased fumonisin resistance. High-level resistance was conferred by FUM18, but not by FUM17. Likewise, strong resistance to FB1 was caused by overexpression of the presumed F. verticillioides “housekeeping” ceramide synthases CER1, CER2, and CER3, located outside the fumonisin cluster, indicating that F. verticillioides possesses a redundant set of insensitive targets as a self-resistance mechanism.
Full article
(This article belongs to the Special Issue Novel Approaches in Mycotoxins Research: Detection, Prevention and Mode of Action)
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