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Toxins
Volume 16
Issue 5
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Toxins, Volume 16, Issue 5 (May 2024) – 30 articles

Cover Story (view full-size image): To assess the potential health risks of mycotoxins in breakfast cereals for children, this study examined the bioaccessibility and intestinal absorption of aflatoxin B1 (AFB1), enniatin B (ENNB), and sterigmatocystin (STG) in cereals. We employed an in vitro gastrointestinal model to investigate how these mycotoxins are released from the cereal during digestion and subsequently absorbed by the intestines. The results revealed that bioaccessibility increased from the stomach to the intestines for AFB1 and STG, but not for ENNB. Bioaccessibility varied across the mycotoxins, ranging from 3.1 to 86.2% for AFB1, 1.5 to 59.3% for STG, and 0.6 to 98.2% for ENNB. Interestingly, milk significantly affected bioaccessibility, and the study found that ENNB and STG exhibited the highest absorption rates when ingested together. View this paper
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13 pages, 801 KiB  
Article
Monoclonal-Antibody-Based Immunoassays for the Mycotoxins NX-2 and NX-3 in Wheat
by Chris M. Maragos, Martha M. Vaughan and Susan P. McCormick
Toxins 2024, 16(5), 231; https://doi.org/10.3390/toxins16050231 - 18 May 2024
Viewed by 1056
Abstract
The fungal infestation of crops can cause major economic losses. Toxins produced by the causative fungi (mycotoxins) represent a potential safety hazard to people and livestock consuming them. One such mycotoxin is deoxynivalenol (DON, also known as vomitoxin), a trichothecene associated with Fusarium [...] Read more.
The fungal infestation of crops can cause major economic losses. Toxins produced by the causative fungi (mycotoxins) represent a potential safety hazard to people and livestock consuming them. One such mycotoxin is deoxynivalenol (DON, also known as vomitoxin), a trichothecene associated with Fusarium Head Blight of wheat. DON is commonly found in cereal crops worldwide. A group of trichothecene mycotoxins closely related to DON, the NX toxins, have been reported to occur in the northeastern United States and southern Canada. While many commercial immunoassays are available to detect DON, there are no rapid screening assays for the NX toxins. We describe the development and isolation of three monoclonal antibodies (mAbs) specific towards two NX toxins: NX-2 and NX-3. The mAbs did not recognize DON or several other closely related trichothecenes. One of the mAbs was selected for development of an enzyme-linked immunosorbent assay (ELISA) for NX-2 and NX-3 in wheat. The dynamic ranges for the assay were 7.7 to 127 μg/kg for NX-2 and 59 μg/kg to 1540 μg/kg for NX-3 in wheat. Recoveries from spiked wheat averaged 84.4% for NX-2 and 99.3% for NX-3, with RSDs of 10.4% and 11.3%, respectively (n = 24). The results suggest that this assay can be used to screen for NX toxins in wheat at levels relevant to human food and animal feed safety. Full article
(This article belongs to the Special Issue Advances in Contamination, Detection and Risk Assessment of Mycotoxins)
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18 pages, 8784 KiB  
Article
Paralytic Shellfish Toxins in Mollusks from Galicia Analyzed by a Fast Refined AOAC 2005.06 Method: Toxicity, Toxin Profile, and Inter-Specific, Spatial, and Seasonal Variations
by Juan Blanco, Juan Pablo Lamas, Fabiola Arévalo, Jorge Correa, Tamara Rodríguez-Cabo and Ángeles Moroño
Toxins 2024, 16(5), 230; https://doi.org/10.3390/toxins16050230 - 15 May 2024
Viewed by 1044
Abstract
Paralytic shellfish poisoning is an important concern for mollusk fisheries, aquaculture, and public health. In Galicia, NW Iberian Peninsula, such toxicity has been monitored for a long time using mouse bioassay. Therefore, little information exists about the precise toxin analogues and their possible [...] Read more.
Paralytic shellfish poisoning is an important concern for mollusk fisheries, aquaculture, and public health. In Galicia, NW Iberian Peninsula, such toxicity has been monitored for a long time using mouse bioassay. Therefore, little information exists about the precise toxin analogues and their possible transformations in diverse mollusk species and environments. After the change in the European PSP reference method, a refinement of the Lawrence method was developed, achieving a 75% reduction in chromatogram run time. Since the beginning of 2021, when this refinement Lawrence method was accredited under the norm UNE-EN ISO/IEC 17025, it has been used in the area to determine the toxin profiles and to estimate PSP toxicity in more than 4500 samples. In this study, we have summarized three years of monitoring results, including interspecific, seasonal, and geographical variability of PSP toxicity and toxin profile. PSP was detected in more than half of the samples analyzed (55%), but only 4.4% of the determinations were above the EU regulatory limit. GTX1,4 was the pair of STX analogs that produced the highest toxicities, but GTX2,3 was found in most samples, mainly due to the reduction of GTX1,4 but also by the higher sensitivity of the method for this pair of analogs. STX seems to be mainly a product of biotransformation from GTX2,3. The studied species (twelve bivalves and one gastropod) accumulated and transformed PSP toxins to a different extent, with most of them showing similar profiles except for Spisula solida and Haliotis tuberculata. Two seasonal peaks of toxicity were found: one in spring-early summer and another in autumn, with slightly different toxin profiles during outbreaks in relation to the toxicity during valleys. In general, both the total toxicity and toxin profiles of the southernmost locations were different from those in the northern part of the Atlantic coast and the Cantabrian Sea, but this general pattern is modified by the PSP history of some specific locations. Full article
(This article belongs to the Special Issue Advances in Marine Toxins: Characterization, Analysis and Surveillance)
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14 pages, 2648 KiB  
Article
Quantitative Analysis of Fungal Contamination of Different Herbal Medicines in China
by Gang Wang, Mingyue Jiao, Junqiang Hu, Yiren Xun, Longyun Chen, Jianbo Qiu, Fang Ji, Yin-Won Lee, Jianrong Shi and Jianhong Xu
Toxins 2024, 16(5), 229; https://doi.org/10.3390/toxins16050229 - 15 May 2024
Cited by 1 | Viewed by 1543
Abstract
Herbal medicines are widely used for clinical purposes worldwide. These herbs are susceptible to phytopathogenic fungal invasion during the culturing, harvesting, storage, and processing stages. The threat of fungal and mycotoxin contamination requires the evaluation of the health risks associated with these herbal [...] Read more.
Herbal medicines are widely used for clinical purposes worldwide. These herbs are susceptible to phytopathogenic fungal invasion during the culturing, harvesting, storage, and processing stages. The threat of fungal and mycotoxin contamination requires the evaluation of the health risks associated with these herbal medicines. In this study, we collected 138 samples of 23 commonly used herbs from 20 regions in China, from which we isolated a total of 200 phytopathogenic fungi. Through morphological observation and ITS sequencing, 173 fungal isolates were identified and classified into 24 genera, of which the predominant genera were Fusarium (27.74%) and Alternaria (20.81%), followed by Epicoccum (11.56%), Nigrospora (7.51%), and Trichocladium (6.84%). Quantitative analysis of the abundance of both Fusarium and Alternaria in herbal medicines via RT-qPCR revealed that the most abundant fungi were found on the herb Taraxacum mongolicum, reaching 300,000 copies/μL for Fusarium and 700 copies/μL for Alternaria. The in vitro mycotoxin productivities of the isolated Fusarium and Alternaria strains were evaluated by using liquid chromatography–tandem mass spectrometry (LC-MS/MS), and it was found that the Fusarium species mainly produced the acetyl forms of deoxynivalenol, while Alternaria species mainly produced altertoxins. These findings revealed widely distributed fungal contamination in herbal medicines and thus raise concerns for the sake of the quality and safety of herbal medicines. Full article
(This article belongs to the Special Issue Toxigenic Fungi and Mycotoxins: From Toxin Biosynthesis to Toxicity Penetration)
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14 pages, 994 KiB  
Systematic Review
Botulinum Toxin for Axial Postural Abnormalities in Parkinson’s Disease: A Systematic Review
by Marialuisa Gandolfi, Carlo Alberto Artusi, Gabriele Imbalzano, Serena Camozzi, Mauro Crestani, Leonardo Lopiano, Michele Tinazzi and Christian Geroin
Toxins 2024, 16(5), 228; https://doi.org/10.3390/toxins16050228 - 15 May 2024
Cited by 1 | Viewed by 1638
Abstract
Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson’s disease and atypical Parkinsonism patients. Despite advancements in diagnosing, assessing, and understanding their pathophysiology, managing these complications remains a significant challenge. Often underestimated by healthcare [...] Read more.
Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson’s disease and atypical Parkinsonism patients. Despite advancements in diagnosing, assessing, and understanding their pathophysiology, managing these complications remains a significant challenge. Often underestimated by healthcare professionals, these disturbances can exacerbate disability. This systematic review assesses botulinum toxin treatments’ effectiveness, alone and with rehabilitation, in addressing APAs in Parkinson’s disease, utilizing MEDLINE (PubMed), Web of Science, and SCOPUS databases for source material. Of the 1087 records retrieved, 16 met the selection criteria. Most research has focused on botulinum toxin (BoNT) as the primary treatment for camptocormia and Pisa syndrome, utilizing mostly observational methods. Despite dose and injection site variations, a common strategy was using electromyography-guided injections, occasionally enhanced with ultrasound. Patients with Pisa syndrome notably saw consistent improvements in APAs and pain. However, studies on the combined effects of botulinum toxin and rehabilitation are limited, and antecollis is significantly under-researched. These findings recommend precise BoNT injections into hyperactive muscles in well-selected patients by skilled clinicians, avoiding compensatory muscles, and underscore the necessity of early rehabilitation. Rehabilitation is crucial in a multidisciplinary approach to managing APAs, highlighting the importance of a multidisciplinary team of experts. Full article
(This article belongs to the Special Issue Application of Botulinum Toxins in Non-spastic and Neurodegenerative Disorders)
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14 pages, 1000 KiB  
Review
A Historical Perspective on Uremia and Uremic Toxins
by Björn Meijers, Ward Zadora and Jerome Lowenstein
Toxins 2024, 16(5), 227; https://doi.org/10.3390/toxins16050227 - 15 May 2024
Viewed by 1660
Abstract
Uremia, also known as uremic syndrome, refers to the clinical symptoms in the final stage of renal failure. The definition of the term has changed over time due to an improved comprehension of the kidney’s function and the advancement of dialysis technology. Here, [...] Read more.
Uremia, also known as uremic syndrome, refers to the clinical symptoms in the final stage of renal failure. The definition of the term has changed over time due to an improved comprehension of the kidney’s function and the advancement of dialysis technology. Here, we aim to present an overview of the various concepts that have developed regarding uremia throughout the years. We provide a comprehensive review of the historical progression starting from the early days of Kolff and his predecessors, continuing with the initial research conducted by Niwa et al., and culminating in the remote sensing hypothesis of Nigam. Additionally, we explore the subsequent investigation into the function of these toxins as signaling molecules in various somatic cells. Full article
(This article belongs to the Special Issue Toxins: 15th Anniversary)
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16 pages, 1678 KiB  
Article
Exposure to a Combination of Fusarium Mycotoxins Leads to Lipid Peroxidation and Influences Antioxidant Defenses, Fatty Acid Composition of Phospholipids, and Renal Histology in Laying Hens
by Szabina Kulcsár, Janka Turbók, György Kövér, Krisztián Balogh, Erika Zándoki, Omeralfaroug Ali, András Szabó and Miklós Mézes
Toxins 2024, 16(5), 226; https://doi.org/10.3390/toxins16050226 - 13 May 2024
Cited by 3 | Viewed by 1039
Abstract
The effects of combined short-term (3 days) exposure to Fusarium mycotoxins at both the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON/3-AcDON/15-AcDON: 5 mg/kg; FB1: 20 mg/kg) and twice the dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg/kg, and FB1 [...] Read more.
The effects of combined short-term (3 days) exposure to Fusarium mycotoxins at both the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON/3-AcDON/15-AcDON: 5 mg/kg; FB1: 20 mg/kg) and twice the dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg/kg, and FB1: 40 mg/kg feed) on the kidneys of laying hens were examined. Our study aimed to investigate how these mycotoxins interacted with membrane lipid fatty acid (FA) composition and lipid peroxidation processes. It was observed that the levels of conjugated dienes and trienes were higher than the control in the low-mix group on day 3, and malondialdehyde concentration was higher on days 2 and 3. The proportion of phospholipid (PL) FAs showed that saturated and monounsaturated FAs increased. Still, both n3 and n6 polyunsaturated FAs decreased significantly on day 2 of exposure in the high-mix group. Among the n3 FAs, the level of docosahexaenoic (C22:6 n3) and among n6 FAs, arachidonic (C20:4 n6) acids decreased mainly on day 2 in the high-mix group. The results suggest that the combined exposure to Fusarium mycotoxins induced lipid peroxidation in the kidneys of laying hens, which resulted in marked changes in the PL FA profile. Histological examination revealed time- and dose-dependent increases as consequences of mycotoxin exposure. Full article
(This article belongs to the Section Mycotoxins)
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17 pages, 5124 KiB  
Article
Intramuscular Botulinum Neurotoxin Serotypes E and A Elicit Distinct Effects on SNAP25 Protein Fragments, Muscular Histology, Spread and Neuronal Transport: An Integrated Histology-Based Study in the Rat
by Vincent Martin, Denis Carre, Heloise Bilbault, Sebastien Oster, Lorenzo Limana, Florian Sebal, Christine Favre-Guilmard, Mikhail Kalinichev, Christian Leveque, Virginie Boulifard, Catherine George and Stephane Lezmi
Toxins 2024, 16(5), 225; https://doi.org/10.3390/toxins16050225 - 12 May 2024
Viewed by 1452
Abstract
Botulinum neurotoxins E (BoNT/E) and A (BoNT/A) act by cleaving Synaptosome-Associated Protein 25 (SNAP25) at two different C-terminal sites, but they display very distinct durations of action, BoNT/E being short acting and BoNT/A long acting. We investigated the duration of action, spread and [...] Read more.
Botulinum neurotoxins E (BoNT/E) and A (BoNT/A) act by cleaving Synaptosome-Associated Protein 25 (SNAP25) at two different C-terminal sites, but they display very distinct durations of action, BoNT/E being short acting and BoNT/A long acting. We investigated the duration of action, spread and neuronal transport of BoNT/E (6.5 ng/kg) and BoNT/A (125 pg/kg) after single intramuscular administrations of high equivalent efficacious doses, in rats, over a 30- or 75-day periods, respectively. To achieve this, we used (i) digit abduction score assay, (ii) immunohistochemistry for SNAP25 (N-ter part; SNAP25N-ter and C-ter part; SNAP25C-ter) and its cleavage sites (cleaved SNAP25; c-SNAP25E and c-SNAP25A) and (iii) muscular changes in histopathology evaluation. Combined in vivo observation and immunohistochemistry analysis revealed that, compared to BoNT/A, BoNT/E induces minimal muscular changes, possesses a lower duration of action, a reduced ability to spread and a decreased capacity to be transported to the lumbar spinal cord. Interestingly, SNAP25C-ter completely disappeared for both toxins during the peak of efficacy, suggesting that the persistence of toxin effects is driven by the persistence of proteases in tissues. These data unveil some new molecular mechanisms of action of the short-acting BoNT/E and long-acting BoNT/A, and reinforce their overall safety profiles. Full article
(This article belongs to the Section Bacterial Toxins)
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16 pages, 3236 KiB  
Article
Unveiling Novel Kunitz- and Waprin-Type Toxins in the Micrurus mipartitus Coral Snake Venom Gland: An In Silico Transcriptome Analysis
by Mónica Saldarriaga-Córdoba, Claudia Clavero-León, Paola Rey-Suarez, Vitelbina Nuñez-Rangel, Ruben Avendaño-Herrera, Stefany Solano-González and Juan F. Alzate
Toxins 2024, 16(5), 224; https://doi.org/10.3390/toxins16050224 - 11 May 2024
Cited by 2 | Viewed by 1317
Abstract
Kunitz-type peptide expression has been described in the venom of snakes of the Viperidae, Elapidae and Colubridae families. This work aimed to identify these peptides in the venom gland transcriptome of the coral snake Micrurus mipartitus. Transcriptomic analysis revealed a high diversity [...] Read more.
Kunitz-type peptide expression has been described in the venom of snakes of the Viperidae, Elapidae and Colubridae families. This work aimed to identify these peptides in the venom gland transcriptome of the coral snake Micrurus mipartitus. Transcriptomic analysis revealed a high diversity of venom-associated Kunitz serine protease inhibitor proteins (KSPIs). A total of eight copies of KSPIs were predicted and grouped into four distinctive types, including short KSPI, long KSPI, Kunitz–Waprin (Ku-WAP) proteins, and a multi-domain Kunitz-type protein. From these, one short KSPI showed high identity with Micrurus tener and Austrelaps superbus. The long KSPI group exhibited similarity within the Micrurus genus and showed homology with various elapid snakes and even with the colubrid Pantherophis guttatus. A third group suggested the presence of Kunitz domains in addition to a whey-acidic-protein-type four-disulfide core domain. Finally, the fourth group corresponded to a transcript copy with a putative 511 amino acid protein, formerly annotated as KSPI, which UniProt classified as SPINT1. In conclusion, this study showed the diversity of Kunitz-type proteins expressed in the venom gland transcriptome of M. mipartitus. Full article
(This article belongs to the Special Issue Transcriptomic and Proteomic Study on Animal Venom: Looking Forward)
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14 pages, 3277 KiB  
Article
Alternariol Monomethyl-Ether Induces Toxicity via Cell Death and Oxidative Stress in Swine Intestinal Epithelial Cells
by Daniela Eliza Marin, Valeria Cristina Bulgaru, AnaMaria Pertea, Iulian Alexandru Grosu, Gina Cecilia Pistol and Ionelia Taranu
Toxins 2024, 16(5), 223; https://doi.org/10.3390/toxins16050223 - 11 May 2024
Cited by 1 | Viewed by 1027
Abstract
Alternariol monomethyl-ether (AME), together with altenuene and alternariol, belongs to the Alternaria mycotoxins group, which can contaminate different substrates, including cereals. The aim of the present study was to obtain a deeper understanding concerning the effects of AME on pig intestinal health using [...] Read more.
Alternariol monomethyl-ether (AME), together with altenuene and alternariol, belongs to the Alternaria mycotoxins group, which can contaminate different substrates, including cereals. The aim of the present study was to obtain a deeper understanding concerning the effects of AME on pig intestinal health using epithelial intestinal cell lines as the data concerning the possible effects of Alternaria toxins on swine are scarce and insufficient for assessing the risk represented by Alternaria toxins for animal health. Our results have shown a dose-related effect on IPEC-1 cell viability, with an IC50 value of 10.5 μM. Exposure to the toxin induced an increase in total apoptotic cells, suggesting that AME induces programmed cell death through apoptosis based on caspase-3/7 activation in IPEC-1 cells. DNA and protein oxidative damage triggered by AME were associated with an alteration of the antioxidant response, as shown by a decrease in the enzymatic activity of catalase and superoxide dismutase. These effects on the oxidative response can be related to an inhibition of the Akt/Nrf2/HO-1 signaling pathway; however, further studies are needed in order to validate these in vitro data using in vivo trials in swine. Full article
(This article belongs to the Section Mycotoxins)
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11 pages, 13594 KiB  
Article
Pulmonary Thromboembolism following Russell’s Viper Bites
by Subramanian Senthilkumaran, Sasikumar Sampath, José R. Almeida, Jarred Williams, Harry F. Williams, Ketan Patel, Ponniah Thirumalaikolundusubramanian and Sakthivel Vaiyapuri
Toxins 2024, 16(5), 222; https://doi.org/10.3390/toxins16050222 - 11 May 2024
Cited by 3 | Viewed by 2158
Abstract
Snakebite envenoming and its resulting complications are serious threats to the health of vulnerable people living in rural areas of developing countries. The knowledge of the heterogeneity of symptoms associated with snakebite envenoming and their management strategies is vital to treat such life-threatening [...] Read more.
Snakebite envenoming and its resulting complications are serious threats to the health of vulnerable people living in rural areas of developing countries. The knowledge of the heterogeneity of symptoms associated with snakebite envenoming and their management strategies is vital to treat such life-threatening complications to save lives. Russell’s viper envenomation induces a diverse range of clinical manifestations from commonly recognised haemotoxic and local effects to several rare conditions that are often not reported. The lack of awareness about these unusual manifestations can affect prompt diagnosis, appropriate therapeutic approaches, and positive outcomes for patients. Here, we report pulmonary thromboembolism that developed in three patients following Russell’s viper envenomation and demonstrate their common clinical features and diagnostic and therapeutic approaches used. All patients showed clinical signs of local (oedema) and systemic (blood coagulation disturbances) envenomation, which were treated using polyvalent antivenom. They exhibited elevated heart rates, breathlessness, and reduced oxygen saturation, which are non-specific but core parameters in the diagnosis of pulmonary embolism. The recognition of pulmonary embolism was also achieved by an electrocardiogram, which showed sinus tachycardia and computed tomography and echocardiogram scans further confirmed this condition. Anti-coagulant treatment using low-molecular-weight heparin offered clinical benefits in these patients. In summary, this report reinforces the broad spectrum of previously unreported consequences of Russell’s viper envenomation. The constant updating of healthcare professionals and the dissemination of major lessons learned in the clinical management of snakebite envenoming through scientific documentation and educational programs are necessary to mitigate the adverse impacts of venomous snakebites in vulnerable communities. Full article
(This article belongs to the Section Animal Venoms)
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12 pages, 914 KiB  
Article
Effectiveness and Safety of OnabotulinumtoxinA in Adolescent Patients with Chronic Migraine
by Laura Gómez-Dabó, Edoardo Caronna, Rut Mas-de-les-Valls, Víctor J. Gallardo, Alicia Alpuente, Marta Torres-Ferrus and Patricia Pozo-Rosich
Toxins 2024, 16(5), 221; https://doi.org/10.3390/toxins16050221 - 11 May 2024
Viewed by 1322
Abstract
Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in adolescents with CM; (2) to review the literature on BTX-A use in the pediatric population. This prospective observational study included patients [...] Read more.
Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in adolescents with CM; (2) to review the literature on BTX-A use in the pediatric population. This prospective observational study included patients under 18 years old with CM treated with BTX-A (PREEMPT protocol) as compassionate use. Demographic, efficacy (monthly headache days—MHD; monthly migraine days—MMD; acute medication days/month—AMDM) and side effect data were collected. A ≥ 50% reduction in MHD was considered as a response. Effectiveness and safety were analyzed at 6 and 12 months. A systematic review of the use of BTX-A in children/adolescents was conducted in July 2023. In total, 20 patients were included (median age 15 years [14.75–17], 70% (14/20) females). The median basal frequencies were 28.8 [20–28] MHD, 18 [10–28] MMD and 10 [7.5–21.2] AMDM. Compared with baseline, at 6 months (n = 20), 11 patients (55%) were responders, with a median reduction in MHD of −20 days/month (p = 0.001). At 12 months (n = 14), eight patients (57.1%) were responders, with a median reduction in MHD of −17.5 days/month (p = 0.002). No adverse effects were reported. The literature search showed similar results. Our data supports the concept that BTX-A is effective, well tolerated, and safe in adolescents with CM resistant to oral preventatives. Full article
(This article belongs to the Section Bacterial Toxins)
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5 pages, 215 KiB  
Editorial
Therapeutic Uses and Efficacy of Botulinum Toxin in Orofacial Medicine: A Dental Perspective
by Kazuya Yoshida and Merete Bakke
Toxins 2024, 16(5), 220; https://doi.org/10.3390/toxins16050220 - 10 May 2024
Cited by 1 | Viewed by 1381
Abstract
Botulinum neurotoxin (BoNT) is the exotoxin of Clostridium botulinum, a Gram-positive, spore-forming bacterium [...] Full article
(This article belongs to the Special Issue Therapeutic Uses and Efficacy of Botulinum Toxin in Orofacial Medicine: From the Standpoint of Dental Professionals)
23 pages, 3625 KiB  
Article
Mutational Analysis of RIP Type I Dianthin-30 Suggests a Role for Arg24 in Endocytosis
by Louisa Schlaak, Christoph Weise, Benno Kuropka and Alexander Weng
Toxins 2024, 16(5), 219; https://doi.org/10.3390/toxins16050219 - 10 May 2024
Viewed by 1045
Abstract
Saponin-mediated endosomal escape is a mechanism that increases the cytotoxicity of type I ribosome-inactivating proteins (type I RIPs). In order to actualize their cytotoxicity, type I RIPs must be released into the cytosol after endocytosis. Without release from the endosomes, type I RIPs [...] Read more.
Saponin-mediated endosomal escape is a mechanism that increases the cytotoxicity of type I ribosome-inactivating proteins (type I RIPs). In order to actualize their cytotoxicity, type I RIPs must be released into the cytosol after endocytosis. Without release from the endosomes, type I RIPs are largely degraded and cannot exert their cytotoxic effects. Certain triterpene saponins are able to induce the endosomal escape of these type I RIPs, thus increasing their cytotoxicity. However, the molecular mechanism underlying the endosomal escape enhancement of type I RIPs by triterpene saponins has not been fully elucidated. In this report, we investigate the involvement of the basic amino acid residues of dianthin-30, a type I RIP isolated from the plant Dianthus caryophyllus L., in endosomal escape enhancement using alanine scanning. Therefore, we designed 19 alanine mutants of dianthin-30. Each mutant was combined with SO1861, a triterpene saponin isolated from the roots of Saponaria officinalis L., and subjected to a cytotoxicity screening in Neuro-2A cells. Cytotoxic screening revealed that dianthin-30 mutants with lysine substitutions did not impair the endosomal escape enhancement. There was one particular mutant dianthin, Arg24Ala, that exhibited significantly reduced synergistic cytotoxicity in three mammalian cell lines. However, this reduction was not based on an altered interaction with SO1861. It was, rather, due to the impaired endocytosis of dianthin Arg24Ala into the cells. Full article
(This article belongs to the Special Issue Biological Activities of Ribosome Inactivating Proteins II)
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38 pages, 4239 KiB  
Review
Monitoring Mycotoxin Exposure in Food-Producing Animals (Cattle, Pig, Poultry, and Sheep)
by Borja Muñoz-Solano, Elena Lizarraga Pérez and Elena González-Peñas
Toxins 2024, 16(5), 218; https://doi.org/10.3390/toxins16050218 - 9 May 2024
Cited by 6 | Viewed by 2281
Abstract
Food-producing animals are exposed to mycotoxins through ingestion, inhalation, or dermal contact with contaminated materials. This exposure can lead to serious consequences for animal health, affects the cost and quality of livestock production, and can even impact human health through foods of animal [...] Read more.
Food-producing animals are exposed to mycotoxins through ingestion, inhalation, or dermal contact with contaminated materials. This exposure can lead to serious consequences for animal health, affects the cost and quality of livestock production, and can even impact human health through foods of animal origin. Therefore, controlling mycotoxin exposure in animals is of utmost importance. A systematic literature search was conducted in this study to retrieve the results of monitoring exposure to mycotoxins in food-producing animals over the last five years (2019–2023), considering both external exposure (analysis of feed) and internal exposure (analysis of biomarkers in biological matrices). The most commonly used analytical technique for both approaches is LC-MS/MS due to its capability for multidetection. Several mycotoxins, especially those that are regulated (ochratoxin A, zearalenone, deoxynivalenol, aflatoxins, fumonisins, T-2, and HT-2), along with some emerging mycotoxins (sterigmatocystin, nivalenol, beauvericin, enniantins among others), were studied in 13,818 feed samples worldwide and were typically detected at low levels, although they occasionally exceeded regulatory levels. The occurrence of multiple exposure is widespread. Regarding animal biomonitoring, the primary objective of the studies retrieved was to study mycotoxin metabolism after toxin administration. Some compounds have been suggested as biomarkers of exposure in the plasma, urine, and feces of animal species such as pigs and poultry. However, further research is required, including many other mycotoxins and animal species, such as cattle and sheep. Full article
(This article belongs to the Special Issue Mycotoxins: Risk Assessment, Biomonitoring and Toxicology)
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17 pages, 5464 KiB  
Article
Chitin Deacetylase Homologous Gene cda Contributes to Development and Aflatoxin Synthesis in Aspergillus flavus
by Xin Zhang, Meifang Wen, Guoqi Li and Shihua Wang
Toxins 2024, 16(5), 217; https://doi.org/10.3390/toxins16050217 - 9 May 2024
Cited by 1 | Viewed by 1289
Abstract
The fungal cell wall serves as the primary interface between fungi and their external environment, providing protection and facilitating interactions with the surroundings. Chitin is a vital structural element in fungal cell wall. Chitin deacetylase (CDA) can transform chitin into chitosan through deacetylation, [...] Read more.
The fungal cell wall serves as the primary interface between fungi and their external environment, providing protection and facilitating interactions with the surroundings. Chitin is a vital structural element in fungal cell wall. Chitin deacetylase (CDA) can transform chitin into chitosan through deacetylation, providing various biological functions across fungal species. Although this modification is widespread in fungi, the biological functions of CDA enzymes in Aspergillus flavus remain largely unexplored. In this study, we aimed to investigate the biofunctions of the CDA family in A. flavus. The A. flavus genome contains six annotated putative chitin deacetylases. We constructed knockout strains targeting each member of the CDA family, including Δcda1, Δcda2, Δcda3, Δcda4, Δcda5, and Δcda6. Functional analyses revealed that the deletion of CDA family members neither significantly affects the chitin content nor exhibits the expected chitin deacetylation function in A. flavus. However, the Δcda6 strain displayed distinct phenotypic characteristics compared to the wild-type (WT), including an increased conidia count, decreased mycelium production, heightened aflatoxin production, and impaired seed colonization. Subcellular localization experiments indicated the cellular localization of CDA6 protein within the cell wall of A. flavus filaments. Moreover, our findings highlight the significance of the CBD1 and CBD2 structural domains in mediating the functional role of the CDA6 protein. Overall, we analyzed the gene functions of CDA family in A. flavus, which contribute to a deeper understanding of the mechanisms underlying aflatoxin contamination and lay the groundwork for potential biocontrol strategies targeting A. flavus. Full article
(This article belongs to the Special Issue Aspergillus flavus and Aflatoxins (Volume III))
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8 pages, 2678 KiB  
Communication
Mindfulness in Facilitating Pelvic Floor Botulinum Toxin Injection in Women with Chronic Pelvic Pain
by Jacqueline V. Aredo, Hannah K. Tandon, Samin Panahi, Vy T. Phan, Rezvan Ameli, Barbara I. Karp and Pamela Stratton
Toxins 2024, 16(5), 216; https://doi.org/10.3390/toxins16050216 - 9 May 2024
Viewed by 1643
Abstract
Botulinum toxin (BoNT) injection can safely be done as an office-based procedure, but can be painful itself, especially when injecting pelvic floor muscles to treat chronic pelvic pain (CPP). Mindfulness interventions may reduce procedure-associated acute anxiety and pain. We applied mindfulness techniques to [...] Read more.
Botulinum toxin (BoNT) injection can safely be done as an office-based procedure, but can be painful itself, especially when injecting pelvic floor muscles to treat chronic pelvic pain (CPP). Mindfulness interventions may reduce procedure-associated acute anxiety and pain. We applied mindfulness techniques to increase the tolerability of office-based pelvic floor BoNT injections in women with CPP. Women enrolled in a clinical trial of BoNT for endometriosis-associated CPP were offered a brief, guided mindfulness session before and/or after transvaginal injection. Anxiety, pain, and dysphoria were rated on a 0–10 numerical rating scale (NRS) before and after each mindfulness session. Eight women underwent mindfulness sessions. Five participants had a session before and two after the transvaginal injection. One participant had two sessions: one before and one after separate injections. All six women completing a session prior to injection had at least moderate anxiety, which lessened after the mindfulness session (median NRS change: −3.3/10). All three women reporting injection-associated pain experienced less intense pain following the post-injection session (median NRS change: −3/10). Three women experiencing dysphoria improved after the session (median NRS change: −3/10). A brief, guided mindfulness session may lessen acute pain, anxiety, and dysphoria associated with office-based transvaginal BoNT injection. Full article
(This article belongs to the Special Issue Uses of Botulinum Toxin Injection in Medicine)
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13 pages, 5541 KiB  
Article
In Vivo and In Vitro Interactions between Exopolysaccharides from Bacillus thuringensis HD270 and Vip3Aa11 Protein
by Tianjiao Ma, Jinqiu Huang, Pengdan Xu, Changlong Shu, Zeyu Wang, Lili Geng and Jie Zhang
Toxins 2024, 16(5), 215; https://doi.org/10.3390/toxins16050215 - 7 May 2024
Viewed by 1251
Abstract
Bacillus thuringiensis (Bt) secretes the nutritional insecticidal protein Vip3Aa11, which exhibits high toxicity against the fall armyworm (Spodoptera frugiperda). The Bt HD270 extracellular polysaccharide (EPS) enhances the toxicity of Vip3Aa11 protoxin against S. frugiperda by enhancing the attachment of brush border [...] Read more.
Bacillus thuringiensis (Bt) secretes the nutritional insecticidal protein Vip3Aa11, which exhibits high toxicity against the fall armyworm (Spodoptera frugiperda). The Bt HD270 extracellular polysaccharide (EPS) enhances the toxicity of Vip3Aa11 protoxin against S. frugiperda by enhancing the attachment of brush border membrane vesicles (BBMVs). However, how EPS-HD270 interacts with Vip3Aa11 protoxin in vivo and the effect of EPS-HD270 on the toxicity of activated Vip3Aa11 toxin are not yet clear. Our results indicated that there is an interaction between mannose, a monosaccharide that composes EPS-HD270, and Vip3Aa11 protoxin, with a dissociation constant of Kd = 16.75 ± 0.95 mmol/L. When EPS-HD270 and Vip3Aa11 protoxin were simultaneously fed to third-instar larvae, laser confocal microscopy observations revealed the co-localization of the two compounds near the midgut wall, which aggravated the damage to BBMVs. EPS-HD270 did not have a synergistic insecticidal effect on the activated Vip3Aa11 protein against S. frugiperda. The activated Vip3Aa11 toxin demonstrated a significantly reduced binding capacity (548.73 ± 82.87 nmol/L) towards EPS-HD270 in comparison to the protoxin (34.96 ± 9.00 nmol/L). Furthermore, this activation diminished the affinity of EPS-HD270 for BBMVs. This study provides important evidence for further elucidating the synergistic insecticidal mechanism between extracellular polysaccharides and Vip3Aa11 protein both in vivo and in vitro. Full article
(This article belongs to the Special Issue Entomopathogenic Bacteria and Toxin: Utilization or Prevention?)
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17 pages, 5095 KiB  
Article
Development and Efficacy of the Antivenom Specific to Severe Envenomations in Morocco and North Africa: Advancements in Scorpion Envenomation Management
by Bouchra Darkaoui, Ines Hilal, Soukaina Khourcha, Ayoub Lafnoune, Salma Chakir, Ayoub Aarab, Abdellah Moustaghfir, Ouafaa Aniq Filali and Naoual Oukkache
Toxins 2024, 16(5), 214; https://doi.org/10.3390/toxins16050214 - 4 May 2024
Cited by 1 | Viewed by 1949
Abstract
Scorpion envenomation poses a global public health issue, with an estimated 1,500,000 cases worldwide annually resulting in 2600 deaths. North Africa, particularly Morocco, experiences severe envenomations, mainly attributed to Androctonus mauretanicus and Buthus occitanus in Morocco, and Buthus occitanus and Androctonus australis hector [...] Read more.
Scorpion envenomation poses a global public health issue, with an estimated 1,500,000 cases worldwide annually resulting in 2600 deaths. North Africa, particularly Morocco, experiences severe envenomations, mainly attributed to Androctonus mauretanicus and Buthus occitanus in Morocco, and Buthus occitanus and Androctonus australis hector in Algeria and Tunisia, with case numbers often underestimated. Current treatment relies mainly on symptomatic approaches, except in Morocco, where management is limited to symptomatic treatment due to controversies regarding specific treatment. In Morocco, between 30,000 and 50,000 scorpion envenomation cases are reported annually, leading to hundreds of deaths, mainly among children. Controversies among clinicians persist regarding the appropriate course of action, often limiting treatments to symptomatic measures. The absence of a specific antivenom for the venoms of the most lethal scorpions further exacerbates the situation. This study aims to address this gap by developing a monovalent antivenom against the endemic and most dangerous scorpion, Androctonus mauretanicus. The antivenom was produced by immunizing albino rabbits with a mixture of Androctonus mauretanicus venom collected from high-risk areas in Morocco. Immunizations were performed by subcutaneous injections at multiple sites near the lymphatic system, following an immunization schedule. Production control of neutralizing antibody titers was conducted through immunodiffusion. Once a sufficient antibody titer was achieved, blood collection was performed, and the recovered plasma underwent affinity chromatography. The efficacy of purified IgG was evaluated by determining the ED50 in mice, complemented by histological and immunohistochemical studies on its ability to neutralize venom-induced tissue alterations and the neutralization of toxins bound to receptors in the studied organs. The monovalent antivenom demonstrated specificity against Androctonus mauretanicus venom and effective cross-protection against the venom of the scorpions Buthus occitanus and Androctonus australis hector, highly implicated in lethal envenomations in the Maghreb. This study shows that the developed monovalent antivenom exhibits notable efficacy against local scorpions and a surprising ability to neutralize the most lethal envenomations in North Africa. These results pave the way for a new, more specific, and promising therapeutic approach to countering severe scorpion envenomations, especially in Morocco, where specific treatment is lacking. Full article
(This article belongs to the Special Issue Passive Immunotherapy and Its Applications in Envenomation and Infectious Diseases: In Tribute to Gaston Ramon (1886–1963))
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17 pages, 1122 KiB  
Article
High-Performance Liquid Chromatography–Fluorescence Detection Method for Ochratoxin A Quantification in Small Mice Sample Volumes: Versatile Application across Diverse Matrices Relevant for Neurodegeneration Research
by Elba Beraza, Maria Serrano-Civantos, Maria Izco, Lydia Alvarez-Erviti, Elena Gonzalez-Peñas and Ariane Vettorazzi
Toxins 2024, 16(5), 213; https://doi.org/10.3390/toxins16050213 - 3 May 2024
Viewed by 1169
Abstract
Ochratoxin A (OTA) is a mycotoxin commonly found in various food products, which poses potential health risks to humans and animals. Recently, more attention has been directed towards its potential neurodegenerative effects. However, there are currently no fully validated HPLC analytical methods established [...] Read more.
Ochratoxin A (OTA) is a mycotoxin commonly found in various food products, which poses potential health risks to humans and animals. Recently, more attention has been directed towards its potential neurodegenerative effects. However, there are currently no fully validated HPLC analytical methods established for its quantification in mice, the primary animal model in this field, that include pivotal tissues in this area of research, such as the intestine and brain. To address this gap, we developed and validated a highly sensitive, rapid, and simple method using HPLC-FLD for OTA determination in mice tissues (kidney, liver, brain, and intestine) as well as plasma samples. The method was rigorously validated for selectivity, linearity, accuracy, precision, recovery, dilution integrity, carry-over effect, stability, and robustness, meeting the validation criteria outlined by FDA and EMA guidelines. Furthermore, the described method enables the quantification of OTA in each individual sample using minimal tissue mass while maintaining excellent recovery values. The applicability of the method was demonstrated in a repeated low-dose OTA study in Balb/c mice, which, together with the inclusion of relevant and less common tissues in the validation process, underscore its suitability for neurodegeneration-related research. Full article
(This article belongs to the Special Issue Novel Approaches in Mycotoxins Research: Detection, Prevention and Mode of Action)
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14 pages, 5471 KiB  
Article
Exposure to Microcystin-LR Promotes Colorectal Cancer Progression by Altering Gut Microbiota and Associated Metabolites in APCmin/+ Mice
by Yuechi Song, Xiaochang Wang, Xiaohui Lu and Ting Wang
Toxins 2024, 16(5), 212; https://doi.org/10.3390/toxins16050212 - 30 Apr 2024
Cited by 3 | Viewed by 1548
Abstract
Microcystins (MCs), toxins generated by cyanobacteria, feature microcystin-LR (MC-LR) as one of the most prevalent and toxic variants in aquatic environments. MC-LR not only causes environmental problems but also presents a substantial risk to human health. This study aimed to investigate the impact [...] Read more.
Microcystins (MCs), toxins generated by cyanobacteria, feature microcystin-LR (MC-LR) as one of the most prevalent and toxic variants in aquatic environments. MC-LR not only causes environmental problems but also presents a substantial risk to human health. This study aimed to investigate the impact of MC-LR on APCmin/+ mice, considered as an ideal animal model for intestinal tumors. We administered 40 µg/kg MC-LR to mice by gavage for 8 weeks, followed by histopathological examination, microbial diversity and metabolomics analysis. The mice exposed to MC-LR exhibited a significant promotion in colorectal cancer progression and impaired intestinal barrier function in the APCmin/+ mice compared with the control. Gut microbial dysbiosis was observed in the MC-LR-exposed mice, manifesting a notable alteration in the structure of the gut microbiota. This included the enrichment of Marvinbryantia, Gordonibacter and Family_XIII_AD3011_group and reductions in Faecalibaculum and Lachnoclostridium. Metabolomics analysis revealed increased bile acid (BA) metabolites in the intestinal contents of the mice exposed to MC-LR, particularly taurocholic acid (TCA), alpha-muricholic acid (α-MCA), 3-dehydrocholic acid (3-DHCA), 7-ketodeoxycholic acid (7-KDCA) and 12-ketodeoxycholic acid (12-KDCA). Moreover, we found that Marvinbryantia and Family_XIII_AD3011_group showed the strongest positive correlation with taurocholic acid (TCA) in the mice exposed to MC-LR. These findings provide new insights into the roles and mechanisms of MC-LR in susceptible populations, providing a basis for guiding values of MC-LR in drinking water. Full article
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19 pages, 806 KiB  
Article
Digital Health Support: Current Status and Future Development for Enhancing Dialysis Patient Care and Empowering Patients
by Bernard Canaud, Andrew Davenport, Hélène Leray-Moragues, Marion Morena-Carrere, Jean Paul Cristol, Jeroen Kooman and Peter Kotanko
Toxins 2024, 16(5), 211; https://doi.org/10.3390/toxins16050211 - 30 Apr 2024
Cited by 2 | Viewed by 2466
Abstract
Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies [...] Read more.
Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments. Full article
(This article belongs to the Special Issue Kidney Replacement Therapy by Hemodialysis: 21st Century Challenges)
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20 pages, 3006 KiB  
Review
Environmental Factors Modulate Saxitoxins (STXs) Production in Toxic Dinoflagellate Alexandrium: An Updated Review of STXs and Synthesis Gene Aspects
by Quynh Thi Nhu Bui, Biswajita Pradhan, Han-Sol Kim and Jang-Seu Ki
Toxins 2024, 16(5), 210; https://doi.org/10.3390/toxins16050210 - 30 Apr 2024
Cited by 3 | Viewed by 1686
Abstract
The marine dinoflagellate Alexandrium is known to form harmful algal blooms (HABs) and produces saxitoxin (STX) and its derivatives (STXs) that cause paralytic shellfish poisoning (PSP) in humans. Cell growth and cellular metabolism are affected by environmental conditions, including nutrients, temperature, light, and [...] Read more.
The marine dinoflagellate Alexandrium is known to form harmful algal blooms (HABs) and produces saxitoxin (STX) and its derivatives (STXs) that cause paralytic shellfish poisoning (PSP) in humans. Cell growth and cellular metabolism are affected by environmental conditions, including nutrients, temperature, light, and the salinity of aquatic systems. Abiotic factors not only engage in photosynthesis, but also modulate the production of toxic secondary metabolites, such as STXs, in dinoflagellates. STXs production is influenced by a variety of abiotic factors; however, the relationship between the regulation of these abiotic variables and STXs accumulation seems not to be consistent, and sometimes it is controversial. Few studies have suggested that abiotic factors may influence toxicity and STXs-biosynthesis gene (sxt) regulation in toxic Alexandrium, particularly in A. catenella, A. minutum, and A. pacificum. Hence, in this review, we focused on STXs production in toxic Alexandrium with respect to the major abiotic factors, such as temperature, salinity, nutrients, and light intensity. This review informs future research on more sxt genes involved in STXs production in relation to the abiotic factors in toxic dinoflagellates. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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16 pages, 3430 KiB  
Article
Peptide Toxins from Antarctica: The Nemertean Predator and Scavenger Parborlasia corrugatus (McIntosh, 1876)
by Erik Jacobsson, Adam A. Strömstedt, Håkan S. Andersson, Conxita Avila and Ulf Göransson
Toxins 2024, 16(5), 209; https://doi.org/10.3390/toxins16050209 - 30 Apr 2024
Viewed by 1529
Abstract
Peptide toxins from marine invertebrates have found use as drugs and in biotechnological applications. Many marine habitats, however, remain underexplored for natural products, and the Southern Ocean is among them. Here, we report toxins from one of the top predators in Antarctic waters: [...] Read more.
Peptide toxins from marine invertebrates have found use as drugs and in biotechnological applications. Many marine habitats, however, remain underexplored for natural products, and the Southern Ocean is among them. Here, we report toxins from one of the top predators in Antarctic waters: the nemertean worm Parborlasia corrugatus (McIntosh, 1876). Transcriptome mining revealed a total of ten putative toxins with a cysteine pattern similar to that of alpha nemertides, four nemertide-beta-type sequences, and two novel full-length parborlysins. Nemertean worms express toxins in the epidermal mucus. Here, the expression was determined by liquid chromatography combined with mass spectrometry. The findings include a new type of nemertide, 8750 Da, containing eight cysteines. In addition, we report the presence of six cysteine-containing peptides. The toxicity of tissue extracts and mucus fractions was tested in an Artemia assay. Notably, significant activity was observed both in tissue and the high-molecular-weight mucus fraction, as well as in a parborlysin fraction. Membrane permeabilization experiments display the membranolytic activity of some peptides, most prominently the parborlysin fraction, with an estimated EC50 of 70 nM. Full article
(This article belongs to the Topic Marine Biotoxins and Bioactive Marine Natural Products)
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15 pages, 4425 KiB  
Article
Specificity of DNA ADP-Ribosylation Reversal by NADARs
by Bara Cihlova, Yang Lu, Andreja Mikoč, Marion Schuller and Ivan Ahel
Toxins 2024, 16(5), 208; https://doi.org/10.3390/toxins16050208 - 28 Apr 2024
Cited by 1 | Viewed by 2203
Abstract
Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR (“NAD- and ADP-ribose”-associated) enzymes reverse guanine ADP-ribosylation and serve as antitoxins in the DarT-NADAR operon. Although NADARs are widespread across prokaryotes, eukaryotes, and viruses, their specificity and broader physiological roles [...] Read more.
Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR (“NAD- and ADP-ribose”-associated) enzymes reverse guanine ADP-ribosylation and serve as antitoxins in the DarT-NADAR operon. Although NADARs are widespread across prokaryotes, eukaryotes, and viruses, their specificity and broader physiological roles remain poorly understood. Using phylogenetic and biochemical analyses, we further explore de-ADP-ribosylation activity and antitoxin functions of NADAR domains. We demonstrate that different subfamilies of NADAR proteins from representative E. coli strains and an E. coli-infecting phage retain biochemical activity while displaying specificity in providing protection from toxic guanine ADP-ribosylation in cells. Furthermore, we identify a myxobacterial enzyme within the YbiA subfamily that functions as an antitoxin for its associated DarT-unrelated ART toxin, which we termed YarT, thus presenting a hitherto uncharacterised ART-YbiA toxin–antitoxin pair. Our studies contribute to the burgeoning field of DNA ADP-ribosylation, supporting its physiological relevance within and beyond bacterial toxin–antitoxin systems. Notably, the specificity and confinement of NADARs to non-mammals infer their potential as highly specific targets for antimicrobial drugs with minimal off-target effects. Full article
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20 pages, 1736 KiB  
Article
An Algoclay-Based Decontaminant Decreases Exposure to Aflatoxin B1, Ochratoxin A, and Deoxynivalenol in a Toxicokinetic Model, as well as Supports Intestinal Morphology, and Decreases Liver Oxidative Stress in Broiler Chickens Fed a Diet Naturally Contaminated with Deoxynivalenol
by Marie Gallissot, Maria A. Rodriguez, Mathias Devreese, Isis Van herteryck, Francesc Molist and Regiane R. Santos
Toxins 2024, 16(5), 207; https://doi.org/10.3390/toxins16050207 - 26 Apr 2024
Cited by 1 | Viewed by 1482
Abstract
The aims of this study were (i) to determine the effect of an algoclay-based decontaminant on the oral availability of three mycotoxins (deoxynivalenol; DON, ochratoxin A; OTA, and aflatoxin B1; AFB1) using an oral bolus model and (ii) to [...] Read more.
The aims of this study were (i) to determine the effect of an algoclay-based decontaminant on the oral availability of three mycotoxins (deoxynivalenol; DON, ochratoxin A; OTA, and aflatoxin B1; AFB1) using an oral bolus model and (ii) to determine the effect of this decontaminant on the performance, intestinal morphology, liver oxidative stress, and metabolism, in broiler chickens fed a diet naturally contaminated with DON. In experiment 1, sixteen 27-day-old male chickens (approximately 1.6 kg body weight; BW) were fasted for 12 h and then given a bolus containing either the mycotoxins (0.5 mg DON/kg BW, 0.25 mg OTA/kg BW, and 2.0 mg AFB1/kg BW) alone (n = 8) or combined with the decontaminant (2.5 g decontaminant/kg feed; circa 240 mg/kg BW) (n = 8). Blood samples were taken between 0 h (before bolus administration) and 24 h post-administration for DON-3-sulphate, OTA, and AFB1 quantification in plasma. The algoclay decontaminant decreased the relative oral bioavailability of DON (39.9%), OTA (44.3%), and AFB1 (64.1%). In experiment 2, one-day-old male Ross broilers (n = 600) were divided into three treatments with ten replicates. Each replicate was a pen with 20 birds. The broiler chickens were fed a control diet with negligible levels of DON (0.19–0.25 mg/kg) or diets naturally contaminated with moderate levels of DON (2.60–2.91 mg/kg), either supplemented or not with an algoclay-based decontaminant (2 g/kg diet). Jejunum villus damage was observed on day 28, followed by villus shortening on d37 in broiler chickens fed the DON-contaminated diet. This negative effect was not observed when the DON-contaminated diet was supplemented with the algoclay-based decontaminant. On d37, the mRNA expression of glutathione synthetase was significantly increased in the liver of broiler chickens fed the DON-contaminated diet. However, its expression was similar to the control when the birds were fed the DON-contaminated diet supplemented with the algoclay-based decontaminant. In conclusion, the algoclay-based decontaminant reduced the systemic exposure of broiler chickens to DON, OTA, and AFB1 in a single oral bolus model. This can be attributed to the binding of the mycotoxins in the gastrointestinal tract. Moreover, dietary contamination with DON at levels between 2.69 and 2.91 mg/kg did not impair production performance but had a negative impact on broiler chicken intestinal morphology and the liver redox system. When the algoclay-based decontaminant was added to the diet, the harm caused by DON was no longer observed. This correlates with the results obtained in the toxicokinetic assay and can be attributed to a decreased absorption of DON. Full article
(This article belongs to the Section Mycotoxins)
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13 pages, 5581 KiB  
Article
Microbial Community Response to Granular Peroxide-Based Algaecide Treatment of a Cyanobacterial Harmful Algal Bloom in Lake Okeechobee, Florida (USA)
by Forrest W. Lefler, Maximiliano Barbosa, David E. Berthold, Rory Roten, West M. Bishop and H. Dail Laughinghouse IV
Toxins 2024, 16(5), 206; https://doi.org/10.3390/toxins16050206 - 26 Apr 2024
Cited by 1 | Viewed by 1507
Abstract
Cyanobacterial harmful algal blooms (cyanoHABs) occur in fresh water globally. These can degrade water quality and produce toxins, resulting in ecological and economic damages. Thus, short-term management methods (i.e., algaecides) are necessary to rapidly mitigate the negative impacts of cyanoHABs. In this study, [...] Read more.
Cyanobacterial harmful algal blooms (cyanoHABs) occur in fresh water globally. These can degrade water quality and produce toxins, resulting in ecological and economic damages. Thus, short-term management methods (i.e., algaecides) are necessary to rapidly mitigate the negative impacts of cyanoHABs. In this study, we assess the efficacy of a hydrogen peroxide-based algaecide (PAK® 27) on a Microcystis dominated bloom which occurred within the Pahokee Marina on Lake Okeechobee, Florida, USA. We observed a significant reduction in chlorophyll a (96.81%), phycocyanin (93.17%), and Microcystis cell counts (99.92%), and a substantial reduction in microcystins (86.7%) 48 h after treatment (HAT). Additionally, there was a significant shift in bacterial community structure 48 HAT, which coincided with an increase in the relative abundance of photosynthetic protists. These results indicate that hydrogen peroxide-based algaecides are an effective treatment method for cyanoHAB control and highlight their effects on non-target microorganisms (i.e., bacteria and protists). Full article
(This article belongs to the Special Issue Harmful Algal Blooms in Waters: Characterization, Monitoring and Management)
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18 pages, 1960 KiB  
Article
In Vitro Digestion and Intestinal Absorption of Mycotoxins Due to Exposure from Breakfast Cereals: Implications for Children’s Health
by Soraia V. M. de Sá, Miguel A. Faria, José O. Fernandes and Sara C. Cunha
Toxins 2024, 16(5), 205; https://doi.org/10.3390/toxins16050205 - 25 Apr 2024
Cited by 1 | Viewed by 1799
Abstract
Breakfast cereals play a crucial role in children’s diets, providing essential nutrients that are vital for their growth and development. Children are known to be more susceptible than adults to the harmful effects of food contaminants, with mycotoxins being a common concern in [...] Read more.
Breakfast cereals play a crucial role in children’s diets, providing essential nutrients that are vital for their growth and development. Children are known to be more susceptible than adults to the harmful effects of food contaminants, with mycotoxins being a common concern in cereals. This study specifically investigated aflatoxin B1 (AFB1), enniatin B (ENNB), and sterigmatocystin (STG), three well-characterized mycotoxins found in cereals. The research aimed to address existing knowledge gaps by comprehensively evaluating the bioaccessibility and intestinal absorption of these three mycotoxins, both individually and in combination, when consumed with breakfast cereals and milk. The in vitro gastrointestinal method revealed patterns in the bioaccessibility of AFB1, ENNB, and STG. Overall, bioaccessibility increased as the food progressed from the stomach to the intestinal compartment, with the exception of ENNB, whose behavior differed depending on the type of milk. The ranking of overall bioaccessibility in different matrices was as follows: digested cereal > cereal with semi-skimmed milk > cereal with lactose-free milk > cereal with soy beverage. Bioaccessibility percentages varied considerably, ranging from 3.1% to 86.2% for AFB1, 1.5% to 59.3% for STG, and 0.6% to 98.2% for ENNB. Overall, the inclusion of milk in the ingested mixture had a greater impact on bioaccessibility compared to consuming the mycotoxins as a single compound or in combination. During intestinal transport, ENNB and STG exhibited the highest absorption rates when ingested together. This study highlights the importance of investigating the combined ingestion and transport of these mycotoxins to comprehensively assess their absorption and potential toxicity in humans, considering their frequent co-occurrence and the possibility of simultaneous exposure. Full article
(This article belongs to the Special Issue Novel Approaches in Mycotoxins Research: Detection, Prevention and Mode of Action)
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17 pages, 2306 KiB  
Article
Advances in the Early Warning of Shellfish Toxification by Dinophysis acuminata
by Alexandra Duarte Silva, Susana Margarida Rodrigues and Lia Godinho
Toxins 2024, 16(5), 204; https://doi.org/10.3390/toxins16050204 - 24 Apr 2024
Viewed by 1142
Abstract
In Western Europe, the incidence of DST is likely the highest globally, posing a significant threat with prolonged bans on shellfish harvesting, mainly caused by species of the dinoflagellate genus Dinophysis. Using a time series from 2014 to 2020, our study aimed [...] Read more.
In Western Europe, the incidence of DST is likely the highest globally, posing a significant threat with prolonged bans on shellfish harvesting, mainly caused by species of the dinoflagellate genus Dinophysis. Using a time series from 2014 to 2020, our study aimed (i) to determine the concentration of D. acuminata in water at which shellfish toxin levels could surpass the regulatory limit (160 µg OA equiv kg−1) and (ii) to assess the predictability of toxic events for timely mitigation actions, especially concerning potential harvesting bans. The analysis considered factors such as (i) overdispersion in the data, (ii) distinct periods of presence and absence, (iii) the persistence of cells, and (iv) the temporal lag between cells in the water and toxins in shellfish. Four generalized additive models were tested, with the Tweedie (TW-GAM) model showing superior performance (>85%) and lower complexity. The results suggest existing thresholds currently employed (200 and 500 cells L−1) are well-suited for the Portuguese coast, supported by empirical evidence (54–79% accuracy). The developed algorithm allows for thresholds to be tailored on a case-by-case basis, offering flexibility for regional variations. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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12 pages, 926 KiB  
Review
Beyond Pain: The Effects of OnabotulinumtoxinA Therapy on Sensitization and Interictal Symptoms in Chronic Migraine
by Paolo Alonge, Filippo Brighina, Simona Maccora, Laura Pilati, Salvatore Di Marco, Davide Ventimiglia, Bruna Maggio, Ivana Cutrò, Cecilia Camarda and Angelo Torrente
Toxins 2024, 16(5), 203; https://doi.org/10.3390/toxins16050203 - 23 Apr 2024
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Abstract
Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of [...] Read more.
Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of headache attacks with central and peripheral sensitization plays a central role and explains some additional symptoms complained about by these patients even in the interictal phase. OnabotulinumtoxinA is a therapy indicated for chronic migraine since it has proven to reduce peripheral sensitization, showing even efficacy on central symptoms. The aim of this narrative review is to present the current evidence regarding the effect of OnabotulinumtoxinA on sensitization and interictal symptoms. Full article
(This article belongs to the Special Issue Botulinum Toxin and Migraine: Goals and Perspectives (Volume II))
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Review
Some Examples of Bacterial Toxins as Tools
by Gudula Schmidt
Toxins 2024, 16(5), 202; https://doi.org/10.3390/toxins16050202 - 23 Apr 2024
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Abstract
Pathogenic bacteria produce diverse protein toxins to disturb the host’s defenses. This includes the opening of epithelial barriers to establish bacterial growth in deeper tissues of the host and to modulate immune cell functions. To achieve this, many toxins share the ability to [...] Read more.
Pathogenic bacteria produce diverse protein toxins to disturb the host’s defenses. This includes the opening of epithelial barriers to establish bacterial growth in deeper tissues of the host and to modulate immune cell functions. To achieve this, many toxins share the ability to enter mammalian cells, where they catalyze the modification of cellular proteins. The enzymatic activity is diverse and ranges from ribosyl- or glycosyl-transferase activity, the deamidation of proteins, and adenylate-cyclase activity to proteolytic cleavage. Protein toxins are highly active enzymes often with tight specificity for an intracellular protein or a protein family coupled with the intrinsic capability of entering mammalian cells. A broad understanding of their molecular mechanisms established bacterial toxins as powerful tools for cell biology. Both the enzymatic part and the pore-forming/protein transport capacity are currently used as tools engineered to study signaling pathways or to transport cargo like labeled compounds, nucleic acids, peptides, or proteins directly into the cytosol. Using several representative examples, this review is intended to provide a short overview of the state of the art in the use of bacterial toxins or parts thereof as tools. Full article
(This article belongs to the Special Issue Biotoxins: Innovative Research Tools to Treat Neuropathologies and Investigate Neurophysiology—In Memory of Professor Matteo Caleo)
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