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Toxins, Volume 15, Issue 11 (November 2023) – 45 articles

Cover Story (view full-size image): Algal toxins pose a serious threat to human and coastal ecosystem health, even if their potential impacts are poorly documented in New Caledonia (NC). In this survey, bivalves and seawater (concentrated through passive samplers) from bays surrounding Noumea, NC, collected during warm and cold seasons, were analyzed for algal toxins using a multi-toxin screening approach. Several groups of marine microalgal toxins were detected for the first time in NC. Internationally regulated toxins of the Azaspiracid, Brevetoxin and Okadaic Acid group by the Codex Alimentarius were detected in addition to five emerging toxin groups, indicating that algal toxins pose a potential risk for the consumers in NC or shellfish export. View this paper
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8 pages, 287 KiB  
Communication
Association between Dental Scores and Saliva Uremic Toxins
Toxins 2023, 15(11), 666; https://doi.org/10.3390/toxins15110666 - 20 Nov 2023
Viewed by 1147
Abstract
Dental health is frequently altered in patients with chronic kidney disease. We conducted a prospective study on dental health in CKD patients with a specific interest in the association between dental health issues and the accumulation of uremic toxins in the saliva. A [...] Read more.
Dental health is frequently altered in patients with chronic kidney disease. We conducted a prospective study on dental health in CKD patients with a specific interest in the association between dental health issues and the accumulation of uremic toxins in the saliva. A total of 88 patients were included in the study, with chronic kidney disease stage 2 to 5 (without kidney replacement). We analysed the total concentrations of eight uremic toxins (trimethylamine N-oxide -TMAO-, Indoxyl Sulfate, P-cresyl-sulfate, Indole 3-acetic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid -CMPF-, Kynurenine, Hippuric acid and Phenylacetylglutamine) and three precursors of uremic toxins (Tyrosine, Phenylalanine and Tryptophan) in the saliva using LC-MS/MS. We observed, for the first time, the association between various dental scores: DMFT, FST, CPITN, and OHIS, and saliva uremic toxins and precursors: TMAO, indoxyl sulfate, or hippuric acid. Further prospective interventional studies are required to confirm our results. Full article
(This article belongs to the Special Issue Toxicity of Uremic Compounds: Recent Research & Development)
14 pages, 11974 KiB  
Article
A Digital Twin Lake Framework for Monitoring and Management of Harmful Algal Blooms
Toxins 2023, 15(11), 665; https://doi.org/10.3390/toxins15110665 - 17 Nov 2023
Cited by 1 | Viewed by 1172
Abstract
Harmful algal blooms (HABs) caused by lake eutrophication and climate change have become one of the most serious problems for the global water environment. Timely and comprehensive data on HABs are essential for their scientific management, a need unmet by traditional methods. This [...] Read more.
Harmful algal blooms (HABs) caused by lake eutrophication and climate change have become one of the most serious problems for the global water environment. Timely and comprehensive data on HABs are essential for their scientific management, a need unmet by traditional methods. This study constructed a novel digital twin lake framework (DTLF) aiming to integrate, represent and analyze multi-source monitoring data on HABs and water quality, so as to support the prevention and control of HABs. In this framework, different from traditional research, browser-based front ends were used to execute the video-based HAB monitoring process, and real-time monitoring in the real sense was realized. On this basis, multi-source monitored results of HABs and water quality were integrated and displayed in the constructed DTLF, and information on HABs and water quality can be grasped comprehensively, visualized realistically and analyzed precisely. Experimental results demonstrate the satisfying frequency of video-based HAB monitoring (once per second) and the valuable results of multi-source data integration and analysis for HAB management. This study demonstrated the high value of the constructed DTLF in accurate monitoring and scientific management of HABs in lakes. Full article
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20 pages, 10566 KiB  
Article
An Assessment of Potential Threats to Human Health from Algae Blooms in the Indian River Lagoon (USA) 2018–2021: Unique Patterns of Cytotoxicity Associated with Toxins
Toxins 2023, 15(11), 664; https://doi.org/10.3390/toxins15110664 - 17 Nov 2023
Viewed by 2076
Abstract
The Indian River Lagoon (IRL), a 156-mile-long estuary located on the eastern coast of Florida, experiences phytoplankton bloom events due to increased seasonal temperatures coupled with anthropogenic impacts. This study aimed to gather data on the toxicity to human cells and to identify [...] Read more.
The Indian River Lagoon (IRL), a 156-mile-long estuary located on the eastern coast of Florida, experiences phytoplankton bloom events due to increased seasonal temperatures coupled with anthropogenic impacts. This study aimed to gather data on the toxicity to human cells and to identify secondary metabolites found in water samples collected in the IRL. Water samples from 20 sites of the IRL were collected during the wet and dry seasons over a three-year period. A panel of cell lines was used to test cytotoxicity. Hemagglutination, hemolysis, and inhibition of protein phosphatase 2A (PP2A) were also measured. Cytotoxic blooms were seen both in the south (Microcystis) and the north (Pyrodinium) of the IRL. Each toxin induced a consistent pattern of cytotoxicity in the panel of human cell lines assayed. During blooms, cytotoxicity due to a single type of toxin is obvious from this pattern. In the absence of blooms, the cytotoxicity seen reflected either a mixture of toxins or it was caused by an unidentified toxin. These observations suggest that other toxins with the potential to be harmful to human health may be present in the IRL. Moreover, the presence of toxins in the IRL is not always associated with blooms of known toxin-producing organisms. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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13 pages, 3351 KiB  
Article
Involvement of Autophagy and Oxidative Stress-Mediated DNA Hypomethylation in Transgenerational Nephrotoxicity Induced in Rats by the Mycotoxin Fumonisin B1
Toxins 2023, 15(11), 663; https://doi.org/10.3390/toxins15110663 - 17 Nov 2023
Viewed by 1103
Abstract
Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, is one of the most common pollutants in natural foods and agricultural crops. It can cause chronic and severe health issues in humans and animals. The aim of this study was to evaluate [...] Read more.
Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, is one of the most common pollutants in natural foods and agricultural crops. It can cause chronic and severe health issues in humans and animals. The aim of this study was to evaluate the transgenerational effects of FB1 exposure on the structure and function of the kidneys in offspring. Virgin female Wistar rats were randomly divided into three groups: group one (control) received sterile water, and groups two and three were intragastrically administered low (20 mg/kg) and high (50 mg/kg) doses of FB1, respectively, from day 6 of pregnancy until delivery. Our results showed that exposure to either dose of FB1 caused histopathological changes, such as atrophy, hypercellularity, hemorrhage, calcification, and a decrease in the glomerular diameter, in both the first and second generations. The levels of the antioxidant markers glutathione, glutathione S-transferase, and catalase significantly decreased, while malondialdehyde levels increased. Moreover, autophagy was induced, as immunofluorescence analysis revealed that LC-3 protein expression was significantly increased in both generations after exposure to either dose of FB1. However, a significant decrease in methyltransferase (DNMT3) protein expression was observed in the first generation in both treatment groups (20 mg/kg and 50 mg/kg), indicating a decrease in DNA methylation as a result of early-life exposure to FB1. Interestingly, global hypomethylation was also observed in the second generation in both treatment groups despite the fact that the mothers of these rats were not exposed to FB1. Thus, early-life exposure to FB1 induced nephrotoxicity in offspring of the first and second generations. The mechanisms of action underlying this transgenerational effect may include oxidative stress, autophagy, and DNA hypomethylation. Full article
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13 pages, 2826 KiB  
Article
Lipopolysaccharides of Brucella suis S2 Impaired the Process of Decidualization in Early Pregnancy in Mice
Toxins 2023, 15(11), 662; https://doi.org/10.3390/toxins15110662 - 16 Nov 2023
Viewed by 1086
Abstract
Brucellosis is a notorious zoonotic disease caused by Brucella, which can lead to reproductive diseases in humans and animals, such as infertility and abortion. Lipopolysaccharides (LPS) are the main virulence factor of Brucella. LPS derived from Brucella are different and non-classical [...] Read more.
Brucellosis is a notorious zoonotic disease caused by Brucella, which can lead to reproductive diseases in humans and animals, such as infertility and abortion. Lipopolysaccharides (LPS) are the main virulence factor of Brucella. LPS derived from Brucella are different and non-classical and are less toxic and less active than LPS isolated from E. coli. However, the effects and possible mechanisms of Brucella LPS-caused pregnancy loss remain to be revealed. In the present study, we investigated the effects of Brucella suis S2 LPS on early pregnancy loss in mice. The results indicated that embryo implantation failure was induced by Brucella LPS treatment in a dose-dependent manner. The injection of Brucella LPS mainly resulted in fibrinolysis in the decidual area of the uterus on the 6th day post coition (dpc), infiltration of large granular cells among the decidual cells near the embryo on the 8th dpc, a large number of gaps in the decidual area, and cell necrosis around the embryo. In addition, the expression of Cyclin D3 mRNA in the uterus on the 7th and 8th dpc and IGFBP-1 mRNA and the progesterone receptor in the uterus on the 6th and 7th dpc were also inhibited. Moreover, the expression of decidualization marker Cyclin D3 and decidualization prolactin-associated protein (dPRP) in endometrial stromal cells were also inhibited by Brucella LPS treatment in vitro. In summary, Brucella LPS affect the process of endometrial decidualization in mice by affecting the structure of the decidua and the expression of decidual marker factors in endometrial stromal cells. Full article
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16 pages, 4746 KiB  
Article
Yessotoxins in Mollusks of the Galician Coast from 2014 to 2022: Variability, Biotransformation, and Resistance to Alkaline Hydrolysis
Toxins 2023, 15(11), 661; https://doi.org/10.3390/toxins15110661 - 16 Nov 2023
Viewed by 935
Abstract
The presence of yessotoxins (YTXs) was analyzed in 10,757 samples of Galician bivalves from 2014 to 2022. Only YTX and 45-OH YTX were found. YTX was detected in 31% of the samples, while 45-OH YTX was found in 11.6% of them. Among the [...] Read more.
The presence of yessotoxins (YTXs) was analyzed in 10,757 samples of Galician bivalves from 2014 to 2022. Only YTX and 45-OH YTX were found. YTX was detected in 31% of the samples, while 45-OH YTX was found in 11.6% of them. Among the samples containing YTX, 45-OH YTX was detected in 37.3% of cases. The maximum recorded levels were 1.4 and 0.16 mg of YTX-equivalentsg−1, for YTX and 45-OH YTX, respectively, which are well below the regulatory limit of the European Union. The YTX and 45-OH YTX toxicities in the raw extracts and extracts subjected to alkaline hydrolysis were strongly and linearly related. Due to the lack of homo-YTX in Galician samples, the effect of alkaline hydrolysis on homo-YTX and 45OH-Homo-YTX was only checked in 23 additional samples, observing no negative effect but a high correlation between raw and hydrolyzed extracts. Hydrolyzed samples can be used instead of raw ones to carry out YTXs determinations in monitoring systems, which may increase the efficiency of those systems where okadaic acid episodes are very frequent and therefore a higher number of hydrolyzed samples are routinely analyzed. The presence of YTX in the studied bivalves varied with the species, with mussels and cockles having the highest percentages of YTX-detected samples. The presence of 45-OH YTX was clearly related to YTX and was detected only in mussels and cockles. Wild populations of mussels contained proportionally more 45-OH YTX than those that were raft-cultured. Spatially, toxin toxicities varied across the sampling area, with higher levels in raft-cultured mussels except those of Ría de Arousa. Ría de Ares (ARE) was the most affected geographical area, although in other northern locations, lower toxin levels were detected. Seasonally, YTX and 45-OH YTX toxicities showed similar patterns, with higher levels in late summer and autumn but lower toxicities of the 45-OH toxin in August. The relationship between the two toxins also varied seasonally, in general with a minimum proportion of 45-OH YTX in July–August but with different maximum levels for raft-cultured and wild mussel populations. Interannually, the average toxicities of YTX decreased from 2014 to 2017 and newly increased from 2018 to 2021, but decreased slightly in 2022. The relationship between 45-OH YTX and YTX also varied over the years, but neither a clear trend nor a similar trend for wild and raft mussels was observed. Full article
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16 pages, 6765 KiB  
Article
A Dynamic and Pseudo-Homogeneous MBs-icELISA for the Early Detection of Aflatoxin B1 in Food and Feed
Toxins 2023, 15(11), 660; https://doi.org/10.3390/toxins15110660 - 16 Nov 2023
Cited by 1 | Viewed by 1066
Abstract
Aflatoxin B1 (AFB1) is one of the most toxic and harmful fungal toxins to humans and animals, and the fundamental way to prevent its entry into humans is to detect its presence in advance. In this paper, the monoclonal antibody [...] Read more.
Aflatoxin B1 (AFB1) is one of the most toxic and harmful fungal toxins to humans and animals, and the fundamental way to prevent its entry into humans is to detect its presence in advance. In this paper, the monoclonal antibody mAbA2-2 was obtained via three-step sample amplification and multi-concentration standard detection using a subcloning method based on the limited dilution method with AFB1 as the target. A dynamic and pseucdo-homogeneous magnetic beads enzyme-linked immunosorbent assay (MBs-icELISA) was established using the prepared antibody as the recognition element and immunomagnetic beads as the antigen carrier. The MBs-icELISA showed good linear correlation in the concentration range of 0.004–10 ng/mL with R2 = 0.99396. The limit of detection (LOD) of the MBs-icELISA for AFB1 was 0.0013 ng/mL. This new ELISA strategy significantly shortened AFB1 detection time through improved sensitivity compared to the conventional ELISA method. Full article
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11 pages, 2949 KiB  
Article
Cyanotoxin Analysis of Air Samples from the Great Salt Lake
Toxins 2023, 15(11), 659; https://doi.org/10.3390/toxins15110659 - 15 Nov 2023
Viewed by 2603
Abstract
The Great Salt Lake in Utah is the largest saline lake in the Western hemisphere and one of the largest terminal lakes in the world. Situated at the eastern edge of the Great Basin, it is a remnant of the freshwater Lake Bonneville [...] Read more.
The Great Salt Lake in Utah is the largest saline lake in the Western hemisphere and one of the largest terminal lakes in the world. Situated at the eastern edge of the Great Basin, it is a remnant of the freshwater Lake Bonneville whose water level precipitously lowered about 12,000 years ago due to a natural break in Red Rock pass to the north. It contains a diverse assemblage of cyanobacteria which vary spatially dependent on salinity. In 1984, the waters of the Great Salt Lake occupied 8500 km2. Nearly four decades later, the waters occupy 2500 km2—a reduction in surface area of 71%. With predominantly westerly winds, there is a potential for the adjacent metropolitan residents to the east to be exposed to airborne cyanobacteria- and cyanotoxin-containing dust. During the summer and fall months of 2022, air and dried sediment samples were collected and assessed for the presence of BMAA which has been identified as a risk factor for ALS. Collection of air samples equivalent to a person breathing for 1 h resulted in BMAA and isomers being found in some air samples, along with their presence in exposed lakebed samples. There was no clear relationship between the presence of these toxins in airborne and adjacent lakebed samples, suggesting that airborne toxins may originate from diffuse rather than point sources. These findings confirm that continued low water levels in the Great Salt Lake may constitute an increasing health hazard for the 2.5 million inhabitants of communities along the Wasatch Front. Full article
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18 pages, 4636 KiB  
Systematic Review
Knowledge about Snake Venoms and Toxins from Colombia: A Systematic Review
Toxins 2023, 15(11), 658; https://doi.org/10.3390/toxins15110658 - 15 Nov 2023
Viewed by 1205
Abstract
Colombia encompasses three mountain ranges that divide the country into five natural regions: Andes, Pacific, Caribbean, Amazon, and Orinoquia. These regions offer an impressive range of climates, altitudes, and landscapes, which lead to a high snake biodiversity. Of the almost 300 snake species [...] Read more.
Colombia encompasses three mountain ranges that divide the country into five natural regions: Andes, Pacific, Caribbean, Amazon, and Orinoquia. These regions offer an impressive range of climates, altitudes, and landscapes, which lead to a high snake biodiversity. Of the almost 300 snake species reported in Colombia, nearly 50 are categorized as venomous. This high diversity of species contrasts with the small number of studies to characterize their venom compositions and natural history in the different ecoregions. This work reviews the available information about the venom composition, isolated toxins, and potential applications of snake species found in Colombia. Data compilation was conducted according to the PRISMA guidelines, and the systematic literature search was carried out in Pubmed/MEDLINE. Venom proteomes from nine Viperidae and three Elapidae species have been described using quantitative analytical strategies. In addition, venoms of three Colubridae species have been studied. Bioactivities reported for some of the venoms or isolated components—such as antibacterial, cytotoxicity on tumoral cell lines, and antiplasmodial properties—may be of interest to develop potential applications. Overall, this review indicates that, despite recent progress in the characterization of venoms from several Colombian snakes, it is necessary to perform further studies on the many species whose venoms remain essentially unexplored, especially those of the poorly known genus Micrurus. Full article
(This article belongs to the Section Animal Venoms)
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15 pages, 7577 KiB  
Article
Characterizing the Influence of a Heterotrophic Bicosoecid Flagellate Pseudobodo sp. on the Dinoflagellate Gambierdiscus balechii
Toxins 2023, 15(11), 657; https://doi.org/10.3390/toxins15110657 - 14 Nov 2023
Viewed by 1125
Abstract
Microbial interactions including competition, mutualism, commensalism, parasitism, and predation, which can be triggered by nutrient acquisition and chemical communication, are universal phenomena in the marine ecosystem. The interactions may influence the microbial population density, metabolism, and even their environmental functions. Herein, we investigated [...] Read more.
Microbial interactions including competition, mutualism, commensalism, parasitism, and predation, which can be triggered by nutrient acquisition and chemical communication, are universal phenomena in the marine ecosystem. The interactions may influence the microbial population density, metabolism, and even their environmental functions. Herein, we investigated the interaction between a heterotrophic bicosoecid flagellate, Pseudobodo sp. (Bicoecea), and a dinoflagellate, Gambierdiscus balechii (Dinophyceae), which is a well-known ciguatera food poisoning (CFP) culprit. The presence of Pseudobodo sp. inhibited the algal proliferation and decreased the cardiotoxicity of zebrafish in the algal extract exposure experiment. Moreover, a significant difference in microbiome abundance was observed in algal cultures with and without Pseudobodo sp. Chemical analysis targeting toxins was performed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with molecular networking (MN), showing a significant alteration in the cellular production of gambierone analogs and some super-carbon chain compounds. Taken together, our results demonstrated the impact of heterotrophic flagellate on the photosynthetic dinoflagellates, revealing the complex dynamics of algal toxin production and the ecological relationships related to dinoflagellates in the marine environment. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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16 pages, 2958 KiB  
Article
Structural Similarities, in Relation with the Cross-Reactivity, of Hymenoptera Allergenic Dipeptidyl Peptidases IV—An Overall Comparison Including a New Dipeptidyl Peptidase IV Sequence from Vespa velutina
Toxins 2023, 15(11), 656; https://doi.org/10.3390/toxins15110656 - 14 Nov 2023
Viewed by 951
Abstract
(1) Background: Dipeptidyl Peptidases IV (DPPIVs), present in many organisms, are minor components in the venoms of Hymenoptera, where they have been identified as cross-reactive allergenic molecules. Considering that the structure of homologous DPPIVs is well characterized, we aimed to explain which regions [...] Read more.
(1) Background: Dipeptidyl Peptidases IV (DPPIVs), present in many organisms, are minor components in the venoms of Hymenoptera, where they have been identified as cross-reactive allergenic molecules. Considering that the structure of homologous DPPIVs is well characterized, we aimed to explain which regions have higher similarity among these proteins and present a comparison among them, including a new Vespa velutina DPPIV sequence. Moreover, two cases of sensitization to DPPIVs in wasp- and honeybee-sensitized patients are presented. (2) Methods: Proteomic analyses have been performed on the venom of the Asian hornet Vespa velutina to demonstrate the sequence of its DPPIV (allergen named Vesp v 3, with sequence accession number P0DRB8, and with the proteomic data available via ProteomeXchange with the identifier PXD046030). A comparison performed through their alignments and analysis of the three-dimensional structure showed a region with higher similarity among Hymenoptera DPPIVs. Additionally, ImmunoCAP™ determinations (including specific inhibition experiments), as well as IgE immunoblotting, are performed to demonstrate the allergenicity of Api m 5 and Ves v 3. (3) Results and Conclusions: The data presented demonstrate that the similarities among Hymenoptera DPPIVs are most likely localized at the C-terminal region of these enzymes. In addition, a higher similarity of the Vespa/Vespula DPPIVs is shown. The clinical cases analyzed demonstrated the allergenicity of Api m 5 and Ves v 3 in the sera of the allergic patients, as well as the presence of this minor component in the preparations used in venom immunotherapy. Full article
(This article belongs to the Special Issue Advances in Venom Immunology and Allergy)
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16 pages, 3116 KiB  
Article
An Exploration of Novel Bioactives from the Venomous Marine Annelid Glycera alba
Toxins 2023, 15(11), 655; https://doi.org/10.3390/toxins15110655 - 14 Nov 2023
Viewed by 1052
Abstract
The immense biodiversity of marine invertebrates makes them high-value targets for the prospecting of novel bioactives. The present study investigated proteinaceous toxins secreted by the skin and proboscis of Glycera alba (Annelida: Polychaeta), whose congenerics G. tridactyla and G. dibranchiata are known to [...] Read more.
The immense biodiversity of marine invertebrates makes them high-value targets for the prospecting of novel bioactives. The present study investigated proteinaceous toxins secreted by the skin and proboscis of Glycera alba (Annelida: Polychaeta), whose congenerics G. tridactyla and G. dibranchiata are known to be venomous. Proteomics and bioinformatics enabled the detection of bioactive proteins that hold potential for biotechnological applications, including toxins like glycerotoxins (GLTx), which can interfere with neuromuscular calcium channels and therefore have value for the development of painkillers, for instance. We also identified proteins involved in the biosynthesis of toxins. Other proteins of interest include venom and toxin-related bioactives like cysteine-rich venom proteins, many of which are known to interfere with the nervous system. Ex vivo toxicity assays with mussel gills exposed to fractionated protein extracts from the skin and proboscis revealed that fractions potentially containing higher-molecular-mass venom proteins can exert negative effects on invertebrate prey. Histopathology, DNA damage and caspase-3 activity suggest significant cytotoxic effects that can be coadjuvated by permeabilizing enzymes such as venom metalloproteinases M12B. Altogether, these encouraging findings show that venomous annelids are important sources of novel bioactives, albeit illustrating the challenges of surveying organisms whose genomes and metabolisms are poorly understood. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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16 pages, 2672 KiB  
Article
The Therapeutic Effect of Botulinum Toxin Type A on Trigeminal Neuralgia: Are There Any Differences between Type 1 versus Type 2 Trigeminal Neuralgia?
Toxins 2023, 15(11), 654; https://doi.org/10.3390/toxins15110654 - 14 Nov 2023
Viewed by 1087
Abstract
Background: Botulinum toxin type A is an effective treatment for trigeminal neuralgia. Moreover, its efficacy in type 2 trigeminal neuralgia and comparative studies between type 1 and type 2 trigeminal neuralgia (TN) still need to be improved. Methods: We treated 40 TN patients [...] Read more.
Background: Botulinum toxin type A is an effective treatment for trigeminal neuralgia. Moreover, its efficacy in type 2 trigeminal neuralgia and comparative studies between type 1 and type 2 trigeminal neuralgia (TN) still need to be improved. Methods: We treated 40 TN patients with onabotulinumtoxinA; 18 had type 1 TN, and 22 had type 2 TN. We compared the baseline pain score with the Visual Analogue Scale (VAS) and paroxysm frequency (number per week) at the baseline with those obtained at 1-month and 3-month follow-ups. Nonetheless, we compared the baseline Penn Facial Pain Scale with the scores obtained at the 1-month follow-up. Results: BoNT/A effectively reduced pain intensity and frequency at the 1-month and 3-month follow-ups. Moreover, the type 1 TN and type 2 TN groups had baseline pain scores of 7.8 ± 1.65 and 8.4 ± 1.1, respectively. Pain significantly improved (p < 0.001) in both groups to 3.1 ± 2.3 (type 1 TN) and 3.5 ± 2.3 (type 2 TN) at the 1-month follow-up and to 3.2 ± 2.5 (type 1 TN) and 3.6 ± 2.5 (type 2 TN) at the 3-month follow-up. There was no difference between the two groups (p 0.345). The baseline paroxysm frequencies (number per week) were 86.7 ± 69.3 and 88.9 ± 62.2 for the type 1 and type 2 TN groups, respectively; they were significantly reduced in both groups at the 1-month and 3-month follow-ups without significant differences between the two groups (p 0.902). The Pain Facial Pain Scale improved at the 1-month follow-up, and no significant differences were found between the two groups. There was a strong correlation between background pain and paroxysm pain intensity (r 0.8, p < 0.001). Conclusions: Botulinum toxin type A effectively reduced the pain, paroxysm frequency, and PFPS scores of type 1 and type 2 trigeminal neuralgia patients without statistically significant differences. Facial asymmetry was the only adverse event. Full article
(This article belongs to the Collection Botulinum Toxins on Human Pain)
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17 pages, 1533 KiB  
Review
Current Knowledge of Individual and Combined Toxicities of Aflatoxin B1 and Fumonisin B1 In Vitro
Toxins 2023, 15(11), 653; https://doi.org/10.3390/toxins15110653 - 13 Nov 2023
Cited by 1 | Viewed by 1413
Abstract
Mycotoxins are considered the most threating natural contaminants in food. Among these mycotoxins, aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are the most prominent fungal metabolites that represent high food safety risks, due to their widespread co-occurrence in several food commodities, and their [...] Read more.
Mycotoxins are considered the most threating natural contaminants in food. Among these mycotoxins, aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are the most prominent fungal metabolites that represent high food safety risks, due to their widespread co-occurrence in several food commodities, and their profound toxic effects on humans. Considering the ethical and more humane animal research, the 3Rs (replacement, reduction, and refinement) principle has been promoted in the last few years. Therefore, this review aims to summarize the research studies conducted up to date on the toxicological effects that AFB1 and FB1 can induce on human health, through the examination of a selected number of in vitro studies. Although the impact of both toxins, as well as their combination, were investigated in different cell lines, the majority of the work was carried out in hepatic cell lines, especially HepG2, owing to the contaminants’ liver toxicity. In all the reviewed studies, AFB1 and FB1 could invoke, after short-term exposure, cell apoptosis, by inducing several pathways (oxidative stress, the mitochondrial pathway, ER stress, the Fas/FasL signaling pathway, and the TNF-α signal pathway). Among these pathways, mitochondria are the primary target of both toxins. The interaction of AFB1 and FB1, whether additive, synergistic, or antagonistic, depends to great extent on FB1/AFB1 ratio. However, it is generally manifested synergistically, via the induction of oxidative stress and mitochondria dysfunction, through the expression of the Bcl-2 family and p53 proteins. Therefore, AFB1 and FB1 mixture may enhance more in vitro toxic effects, and carry a higher significant risk factor, than the individual presence of each toxin. Full article
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16 pages, 4416 KiB  
Article
Characterization of Fusarium verticillioides Med1 LxxLL Motif Involved in Fumonisin Biosynthesis
Toxins 2023, 15(11), 652; https://doi.org/10.3390/toxins15110652 - 13 Nov 2023
Viewed by 948
Abstract
The Med1 transcriptional coactivator is a crucial component of the Mediator middle complex, which regulates the expression of specific genes involved in cell development, differentiation, reproduction, and homeostasis. The Med1 LxxLL motif, a five-amino-acid peptide sequence, is essential for Med1-mediated gene expression. Our [...] Read more.
The Med1 transcriptional coactivator is a crucial component of the Mediator middle complex, which regulates the expression of specific genes involved in cell development, differentiation, reproduction, and homeostasis. The Med1 LxxLL motif, a five-amino-acid peptide sequence, is essential for Med1-mediated gene expression. Our previous study revealed that the disruption of the Med1 subunit leads to a significant increase in fumonisin B1 (FB1) production in the maize pathogen Fusarium verticillioides. However, our understanding of how Med1 regulates FB1 biosynthesis in F. verticillioides, particularly through the Med1 LxxLL motifs, remains limited. To characterize the role of LxxLL motifs, we generated a series of Med1 LxxLL deletion and amino acid substitution mutants. These mutants exhibited impaired mycelial growth and conidia germination while demonstrating enhanced conidia production and virulence. Similar to the Med1 deletion mutant, Med1 LxxLL motif mutants also exhibited increased FB1 biosynthesis in F. verticillioides. Proteomic profiling revealed that the Med1 LxxLL motif regulated the biosynthesis of several key substances that affected FB1 production, including starch and carotenoid. Subsequent studies demonstrated that the production of amylopectin, which is strongly linked to FB1 biosynthesis, was significantly increased in Med1 LxxLL motif mutants. In addition, the disruption of carotenoid metabolic genes decreased carotenoid content, thus stimulating FB1 biosynthesis in F. verticillioides. Taken together, our results provide valuable insights into how the Med1 LxxLL motif regulates FB1 biosynthesis in the mycotoxigenic fungus F. verticillioides. Full article
(This article belongs to the Section Mycotoxins)
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13 pages, 1400 KiB  
Article
Lamium album Flower Extracts: A Novel Approach for Controlling Fusarium Growth and Mycotoxin Biosynthesis
Toxins 2023, 15(11), 651; https://doi.org/10.3390/toxins15110651 - 13 Nov 2023
Viewed by 1115
Abstract
Lamium album is a medicinal flowering plant that is rich in bioactive compounds with various biological properties. Fusarium species, known for causing significant crop losses and mycotoxin contamination, pose threats to food safety and human health. While synthetic fungicides are commonly employed for [...] Read more.
Lamium album is a medicinal flowering plant that is rich in bioactive compounds with various biological properties. Fusarium species, known for causing significant crop losses and mycotoxin contamination, pose threats to food safety and human health. While synthetic fungicides are commonly employed for fungal management, their environmental impact prompts the ongoing development of alternative methods. This study aimed to evaluate the efficacy of L. album flower extracts in inhibiting the in vitro growth and biosynthesis of mycotoxins by Fusarium culmorum and F. proliferatum strains. The extracts were obtained by supercritical fluid extraction using CO2 (SC-CO2). The effects of various concentrations (2.5, 5, 7.5, and 10%) were assessed on a potato dextrose agar (PDA) medium using the “poisoning” technique. L. album flower extracts reduced mycelium growth by 0 to 30.59% for F. culmorum and 27.71 to 42.97% for F. proliferatum. Ergosterol content was reduced by up to 88.87% for F. culmorum and 93.17% for F. proliferatum. Similarly, the amounts of synthesized mycotoxins produced by both strains were also lower compared to control cultures. These findings are a preliminary phase for further in vivo tests planned to determine the fungistatic effect of L. album flower extracts on cereal substrates as seedlings incubated in controlled environments and under field conditions. Their phytotoxicity and biological stability, as well as the possibility of formulating a bio-preparation to protect cereals against Fusarium infections, will be evaluated. Full article
(This article belongs to the Section Mycotoxins)
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27 pages, 10762 KiB  
Article
Venomous Noodles: The Evolution of Toxins in Nemertea through Positive Selection and Gene Duplication
Toxins 2023, 15(11), 650; https://doi.org/10.3390/toxins15110650 - 12 Nov 2023
Viewed by 1114
Abstract
Some, probably most and perhaps all, members of the phylum Nemertea are poisonous, documented so far from marine and benthic specimens. Although the toxicity of these animals has been long known, systematic studies on the characterization of toxins, mechanisms of toxicity, and toxin [...] Read more.
Some, probably most and perhaps all, members of the phylum Nemertea are poisonous, documented so far from marine and benthic specimens. Although the toxicity of these animals has been long known, systematic studies on the characterization of toxins, mechanisms of toxicity, and toxin evolution for this group are scarce. Here, we present the first investigation of the molecular evolution of toxins in Nemertea. Using a proteo-transcriptomic approach, we described toxins in the body and poisonous mucus of the pilidiophoran Lineus sanguineus and the hoplonemertean Nemertopsis pamelaroeae. Using these new and publicly available transcriptomes, we investigated the molecular evolution of six selected toxin gene families. In addition, we also characterized in silico the toxin genes found in the interstitial hoplonemertean, Ototyphlonemertes erneba, a meiofaunal taxa. We successfully identified over 200 toxin transcripts in each of these species. Evidence of positive selection and gene duplication was observed in all investigated toxin genes. We hypothesized that the increased rates of gene duplications observed for Pilidiophora could be involved with the expansion of toxin genes. Studies concerning the natural history of Nemertea are still needed to understand the evolution of their toxins. Nevertheless, our results show evolutionary mechanisms similar to other venomous groups. Full article
(This article belongs to the Section Animal Venoms)
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15 pages, 2212 KiB  
Article
Renocardiac Effects of p-Cresyl Sulfate Administration in Acute Kidney Injury Induced by Unilateral Ischemia and Reperfusion Injury In Vivo
Toxins 2023, 15(11), 649; https://doi.org/10.3390/toxins15110649 - 10 Nov 2023
Viewed by 1213
Abstract
The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected [...] Read more.
The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected to AKI induced by ischemia and reperfusion (IR) injury. C57BL6 mice were subjected to distinct protocols: (i) administration with PCS (20, 40, or 60 mg/L/day) for 15 days and (ii) AKI due to unilateral IR injury associated with PCS administration for 15 days. The 20 mg/L dose of PCS led to a decrease in renal mass, an increase in the gene expression of Cystatin C and kidney injury molecule 1 (KIM-1), and a decrease in the α-actin in the heart. During AKI, PCS increased the renal injury biomarkers compared to control; however, it did not exacerbate these markers. Furthermore, PCS did not enhance the cardiac hypertrophy observed after 15 days of IR. An increase, but not potentialized, in the cardiac levels of interleukin (IL)-1β and IL-6 in the IR group treated with PCS, as well as in the injured kidney, was also noticed. In short, PCS administration did not intensify kidney injury, inflammation, and cardiac outcomes after AKI. Full article
(This article belongs to the Special Issue Toxicity of Uremic Compounds: Recent Research & Development)
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7 pages, 529 KiB  
Communication
Preliminary Insights of Brazilian Snake Venom Metalloproteomics
Toxins 2023, 15(11), 648; https://doi.org/10.3390/toxins15110648 - 10 Nov 2023
Viewed by 954
Abstract
Snakebite envenoming is one of the most significantly neglected tropical diseases in the world. The lack of diagnosis/prognosis methods for snakebite is one of our motivations to develop innovative technological solutions for Brazilian health. The objective of this work was to evaluate the [...] Read more.
Snakebite envenoming is one of the most significantly neglected tropical diseases in the world. The lack of diagnosis/prognosis methods for snakebite is one of our motivations to develop innovative technological solutions for Brazilian health. The objective of this work was to evaluate the protein and metallic ion composition of Crotalus durissus terrificus, Bothrops jararaca, B. alternatus, B. jararacussu, B. moojeni, B. pauloensis, and Lachesis muta muta snake venoms. Brazilian snake venoms were subjected to the shotgun proteomic approach using mass spectrometry, and metal ion analysis was performed by atomic spectrometry. Shotgun proteomics has shown three abundant toxin classes (PLA2, serine proteases, and metalloproteinases) in all snake venoms, and metallic ions analysis has evidenced that the Cu2+ ion is present exclusively in the L. m. muta venom; Ca2+ and Mg2+ ions have shown a statistical difference between the species of Bothrops and Crotalus genus, whereas the Zn2+ ion presented a statistical difference among all species studied in this work. In addition, Mg2+ ions have shown 42 times more in the C. d. terrificus venom when compared to the average concentration in the other genera. Though metal ions are a minor fraction of snake venoms, several venom toxins depend on them. We believe that these non-protein fractions are capable of assisting in the development of unprecedented diagnostic devices for Brazilian snakebites. Full article
(This article belongs to the Special Issue Proteomic Analysis and Functional Characterization of Venom)
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13 pages, 440 KiB  
Article
Effects of the Toxic Non-Protein Amino Acid β-Methylamino-L-Alanine (BMAA) on Intracellular Amino Acid Levels in Neuroblastoma Cells
Toxins 2023, 15(11), 647; https://doi.org/10.3390/toxins15110647 - 09 Nov 2023
Cited by 1 | Viewed by 1126
Abstract
The cyanobacterial non-protein amino acid (AA) β-Methylamino-L-alanine (BMAA) is considered to be a neurotoxin. BMAA caused histopathological changes in brains and spinal cords of primates consistent with some of those seen in early motor neuron disease; however, supplementation with L-serine protected against some [...] Read more.
The cyanobacterial non-protein amino acid (AA) β-Methylamino-L-alanine (BMAA) is considered to be a neurotoxin. BMAA caused histopathological changes in brains and spinal cords of primates consistent with some of those seen in early motor neuron disease; however, supplementation with L-serine protected against some of those changes. We examined the impact of BMAA on AA concentrations in human neuroblastoma cells in vitro. Cells were treated with 1000 µM BMAA and intracellular free AA concentrations in treated and control cells were compared at six time-points over a 48 h culture period. BMAA had a profound effect on intracellular AA levels at specific time points but in most cases, AA homeostasis was re-established in the cell. The most heavily impacted amino acid was serine which was depleted in BMAA-treated cells from 9 h onwards. Correction of serine depletion could be a factor in the observation that supplementation with L-serine protects against BMAA toxicity in vitro and in vivo. AAs that could potentially be involved in protection against BMAA-induced oxidation such as histidine, tyrosine, and phenylalanine were depleted in cells at later time points. Full article
(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)
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12 pages, 294 KiB  
Article
Assessment of the Adverse Health Effects of Aflatoxin Exposure from Unpackaged Peanut Oil in Guangdong, China
Toxins 2023, 15(11), 646; https://doi.org/10.3390/toxins15110646 - 09 Nov 2023
Viewed by 1287
Abstract
Aflatoxins are liver carcinogens and are common contaminants in unpackaged peanut (UPP) oil. However, the health risks associated with consuming aflatoxins in UPP oil remain unclear. In this study, aflatoxin contamination in 143 UPP oil samples from Guangdong Province were assessed via liquid [...] Read more.
Aflatoxins are liver carcinogens and are common contaminants in unpackaged peanut (UPP) oil. However, the health risks associated with consuming aflatoxins in UPP oil remain unclear. In this study, aflatoxin contamination in 143 UPP oil samples from Guangdong Province were assessed via liquid chromatography–tandem mass spectrometry (LC-MS). We also recruited 168 human subjects, who consumed this oil, to measure their liver functions and lipid metabolism status. Aflatoxin B1 (AFB1) was detected in 79.72% of the UPP oil samples, with levels ranging from 0.02 to 174.13 μg/kg. The average daily human intake of AFB1 from UPP oil was 3.14 ng/kg·bw/day; therefore, the incidence of liver cancer, caused by intake of 1 ng/kg·bw/day AFB1, was estimated to be 5.32 cases out of every 100,000 persons per year. Meanwhile, Hepatitis B virus (HBV) infection and AFB1 exposure exerted a synergistic effect to cause liver dysfunction. In addition, the triglycerides (TG) abnormal rate was statistically significant when using AFB1 to estimate daily intake (EDI) quartile spacing grouping (p = 0.011). In conclusion, high aflatoxin exposure may exacerbate the harmful effects of HBV infection on liver function. Contamination of UPP oil with aflatoxins in Guangdong urgently requires more attention, and public health management of the consumer population is urgently required. Full article
(This article belongs to the Collection Aflatoxins)
33 pages, 1542 KiB  
Review
Current Trends in Mycotoxin Detection with Various Types of Biosensors
Toxins 2023, 15(11), 645; https://doi.org/10.3390/toxins15110645 - 06 Nov 2023
Viewed by 1423
Abstract
One of the most important tasks in food safety is to properly manage the investigation of mycotoxin contamination in agricultural products and foods made from them, as well as to prevent its occurrence. Monitoring requires a wide range of analytical methods, from expensive [...] Read more.
One of the most important tasks in food safety is to properly manage the investigation of mycotoxin contamination in agricultural products and foods made from them, as well as to prevent its occurrence. Monitoring requires a wide range of analytical methods, from expensive analytical procedures with high-tech instrumentation to significantly cheaper biosensor developments or even single-use assays suitable for on-site monitoring. This review provides a summary of the development directions over approximately a decade and a half, grouped according to the biologically sensitive components used. We provide an overview of the use of antibodies, molecularly imprinted polymers, and aptamers, as well as the diversity of biosensors and their applications within the food industry. We also mention the possibility of determining multiple toxins side by side, which would significantly reduce the time required for the analyses. Full article
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13 pages, 989 KiB  
Article
Field Evaluation of Cotton Expressing Mpp51Aa2 as a Management Tool for Cotton Fleahoppers, Pseudatomoscelis seriatus (Reuter)
Toxins 2023, 15(11), 644; https://doi.org/10.3390/toxins15110644 - 05 Nov 2023
Cited by 1 | Viewed by 1314
Abstract
The cotton fleahopper (Pseudatomoscelis seriatus Reuter) is considered a highly economically damaging pest of cotton (Gossypium hirsutum L.) in Texas and Oklahoma. Current control methods rely heavily on the use of foliar-applied chemical insecticides, but considering the cost of insecticides and [...] Read more.
The cotton fleahopper (Pseudatomoscelis seriatus Reuter) is considered a highly economically damaging pest of cotton (Gossypium hirsutum L.) in Texas and Oklahoma. Current control methods rely heavily on the use of foliar-applied chemical insecticides, but considering the cost of insecticides and the critical timeliness of applications, chemical control methods are often not optimized to reduce potential yield losses from this pest. The Bacillus thuringiensis (Bt) Mpp51Aa2 (formerly Cry51Aa2.834_16) protein has proven effective against thrips and plant bugs with piercing and sucking feeding behaviors, but the impact of this toxin on cotton fleahoppers has not been investigated. To evaluate the Mpp51Aa2 trait effectiveness towards the cotton fleahopper, field trials were conducted in 2019, 2020, and 2021, comparing a cotton cultivar containing the Mpp51Aa2 trait to a non-traited isoline cultivar under insecticide-treated and untreated conditions. Populations of cotton fleahopper nymphs and adults were estimated weekly by visually inspecting cotton terminals. Square retention was also assessed during the first week of bloom to provide some insight on how the Bt trait may influence yield. While cotton fleahopper population differences between the traited and non-traited plants were not consistently noted during the pre-bloom squaring period, there was a consistent increase in square retention in cotton expressing Mpp51Aa2 relative to non-traited cotton. Additionally, cotton expressing Mpp51Aa2 offered similar square protection relative to non-traited cotton treated with insecticides for the cotton fleahopper. These findings indicate that the Mpp51Aa2 protein should provide benefits of delayed nymphal growth, population suppression, and increased square retention. Full article
(This article belongs to the Special Issue Bacillus thuringiensis: A Broader View of Its Biocidal Activity)
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19 pages, 4903 KiB  
Article
A Colonic Organoid Model Challenged with the Large Toxins of Clostridioides difficile TcdA and TcdB Exhibit Deregulated Tight Junction Proteins
Toxins 2023, 15(11), 643; https://doi.org/10.3390/toxins15110643 - 04 Nov 2023
Viewed by 1281
Abstract
Background: Clostridioides difficile toxins TcdA and TcdB are responsible for diarrhea and colitis. Lack of functional studies in organoid models of the gut prompted us to elucidate the toxin’s effects on epithelial barrier function and the molecular mechanisms for diarrhea and inflammation. Methods: [...] Read more.
Background: Clostridioides difficile toxins TcdA and TcdB are responsible for diarrhea and colitis. Lack of functional studies in organoid models of the gut prompted us to elucidate the toxin’s effects on epithelial barrier function and the molecular mechanisms for diarrhea and inflammation. Methods: Human adult colon organoids were cultured on membrane inserts. Tight junction (TJ) proteins and actin cytoskeleton were analyzed for expression via Western blotting and via confocal laser-scanning microscopy for subcellular localization. Results: Polarized intestinal organoid monolayers were established from stem cell-containing colon organoids to apply toxins from the apical side and to perform functional measurements in the organoid model. The toxins caused a reduction in transepithelial electrical resistance in human colonic organoid monolayers with sublethal concentrations. Concomitantly, we detected increased paracellular permeability fluorescein and FITC-dextran-4000. Human colonic organoid monolayers exposed to the toxins exhibited redistribution of barrier-forming TJ proteins claudin-1, -4 and tricellulin, whereas channel-forming claudin-2 expression was increased. Perijunctional F-actin cytoskeleton organization was affected. Conclusions: Adult stem cell-derived human colonic organoid monolayers were applicable as a colon infection model for electrophysiological measurements. The TJ changes noted can explain the epithelial barrier dysfunction and diarrhea in patients, as well as increased entry of luminal antigens triggering inflammation. Full article
(This article belongs to the Special Issue Enterotoxins and Mucosal Pathomechanisms)
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16 pages, 3213 KiB  
Article
Seasonal Single-Site Sampling Reveals Large Diversity of Marine Algal Toxins in Coastal Waters and Shellfish of New Caledonia (Southwestern Pacific)
Toxins 2023, 15(11), 642; https://doi.org/10.3390/toxins15110642 - 03 Nov 2023
Viewed by 1013
Abstract
Algal toxins pose a serious threat to human and coastal ecosystem health, even if their potential impacts are poorly documented in New Caledonia (NC). In this survey, bivalves and seawater (concentrated through passive samplers) from bays surrounding Noumea, NC, collected during the warm [...] Read more.
Algal toxins pose a serious threat to human and coastal ecosystem health, even if their potential impacts are poorly documented in New Caledonia (NC). In this survey, bivalves and seawater (concentrated through passive samplers) from bays surrounding Noumea, NC, collected during the warm and cold seasons were analyzed for algal toxins using a multi-toxin screening approach. Several groups of marine microalgal toxins were detected for the first time in NC. Okadaic acid (OA), azaspiracid-2 (AZA2), pectenotoxin-2 (PTX2), pinnatoxin-G (PnTX-G), and homo-yessotoxin (homo-YTX) were detected in seawater at higher levels during the summer. A more diversified toxin profile was found in shellfish with brevetoxin-3 (BTX3), gymnodimine-A (GYM-A), and 13-desmethyl spirolide-C (SPX1), being confirmed in addition to the five toxin groups also found in seawater. Diarrhetic and neurotoxic toxins did not exceed regulatory limits, but PnTX-G was present at up to the limit of the threshold recommended by the French Food Safety Authority (ANSES, 23 μg kg−1). In the present study, internationally regulated toxins of the AZA-, BTX-, and OA-groups by the Codex Alimentarius were detected in addition to five emerging toxin groups, indicating that algal toxins pose a potential risk for the consumers in NC or shellfish export. Full article
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17 pages, 2152 KiB  
Article
Conotoxin Prediction: New Features to Increase Prediction Accuracy
Toxins 2023, 15(11), 641; https://doi.org/10.3390/toxins15110641 - 03 Nov 2023
Viewed by 1255
Abstract
Conotoxins are toxic, disulfide-bond-rich peptides from cone snail venom that target a wide range of receptors and ion channels with multiple pathophysiological effects. Conotoxins have extraordinary potential for medical therapeutics that include cancer, microbial infections, epilepsy, autoimmune diseases, neurological conditions, and cardiovascular disorders. [...] Read more.
Conotoxins are toxic, disulfide-bond-rich peptides from cone snail venom that target a wide range of receptors and ion channels with multiple pathophysiological effects. Conotoxins have extraordinary potential for medical therapeutics that include cancer, microbial infections, epilepsy, autoimmune diseases, neurological conditions, and cardiovascular disorders. Despite the potential for these compounds in novel therapeutic treatment development, the process of identifying and characterizing the toxicities of conotoxins is difficult, costly, and time-consuming. This challenge requires a series of diverse, complex, and labor-intensive biological, toxicological, and analytical techniques for effective characterization. While recent attempts, using machine learning based solely on primary amino acid sequences to predict biological toxins (e.g., conotoxins and animal venoms), have improved toxin identification, these methods are limited due to peptide conformational flexibility and the high frequency of cysteines present in toxin sequences. This results in an enumerable set of disulfide-bridged foldamers with different conformations of the same primary amino acid sequence that affect function and toxicity levels. Consequently, a given peptide may be toxic when its cysteine residues form a particular disulfide-bond pattern, while alternative bonding patterns (isoforms) or its reduced form (free cysteines with no disulfide bridges) may have little or no toxicological effects. Similarly, the same disulfide-bond pattern may be possible for other peptide sequences and result in different conformations that all exhibit varying toxicities to the same receptor or to different receptors. We present here new features, when combined with primary sequence features to train machine learning algorithms to predict conotoxins, that significantly increase prediction accuracy. Full article
(This article belongs to the Special Issue Conotoxins: Evolution, Classifications and Targets)
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13 pages, 3491 KiB  
Article
Characteristics of Shiga Toxin-Producing Escherichia coli Circulating in Asymptomatic Food Handlers
Toxins 2023, 15(11), 640; https://doi.org/10.3390/toxins15110640 - 02 Nov 2023
Viewed by 1406
Abstract
Shiga toxin-producing Escherichia coli (STEC) is a foodborne zoonotic pathogen that causes diarrhea, hemorrhagic colitis (HC), and hemolytic uremic syndrome (HUS) worldwide. Since the infection can be asymptomatic, the circulation of STEC in some asymptomatic carriers, especially in healthy-food-related professionals, is not yet [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) is a foodborne zoonotic pathogen that causes diarrhea, hemorrhagic colitis (HC), and hemolytic uremic syndrome (HUS) worldwide. Since the infection can be asymptomatic, the circulation of STEC in some asymptomatic carriers, especially in healthy-food-related professionals, is not yet well understood. In this study, a total of 3987 anal swab samples from asymptomatic food handlers were collected, and ten swabs recovered STEC strains (0.251%). Of the ten STEC isolates, seven serotypes and eight sequence types (ST) were determined using whole genome sequencing (WGS). Two stx1 subtypes (stx1a and stx1c) and four stx2 subtypes (stx2a, stx2b, stx2d, and stx2e) were detected. Seven different insertion sites were found in fourteen Stx prophages, and the dmsB and yfhL were the newly identified insertion sites. The ten strains showed the variable Stx transcription levels after the mitomycin C induction. The whole-genome phylogeny indicated that the strains from the asymptomatic food handlers were genetically distant from the strains of HUS patients. The STEC isolates circulating in asymptomatic carriers might pose a low potential to cause disease. Full article
(This article belongs to the Collection Shiga Toxins)
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15 pages, 2411 KiB  
Article
A Direct Analysis of β-N-methylamino-l-alanine Enantiomers and Isomers and Its Application to Cyanobacteria and Marine Mollusks
Toxins 2023, 15(11), 639; https://doi.org/10.3390/toxins15110639 - 01 Nov 2023
Viewed by 1496
Abstract
Of the wide variety of toxic compounds produced by cyanobacteria, the neurotoxic amino acid β-N-methylamino-l-alanine (BMAA) has attracted attention as a result of its association with chronic human neurodegenerative diseases such as ALS and Alzheimer’s. Consequently, specific detection methods [...] Read more.
Of the wide variety of toxic compounds produced by cyanobacteria, the neurotoxic amino acid β-N-methylamino-l-alanine (BMAA) has attracted attention as a result of its association with chronic human neurodegenerative diseases such as ALS and Alzheimer’s. Consequently, specific detection methods are required to assess the presence of BMAA and its isomers in environmental and clinical materials, including cyanobacteria and mollusks. Although the separation of isomers such as β-amino-N-methylalanine (BAMA), N-(2-aminoethyl)glycine (AEG) and 2,4-diaminobutyric acid (DAB) from BMAA has been demonstrated during routine analysis, a further compounding factor is the potential presence of enantiomers for some of these isomers. Current analytical methods for BMAA mostly do not discriminate between enantiomers, and the chiral configuration of BMAA in cyanobacteria is still largely unexplored. To understand the potential for the occurrence of D-BMAA in cyanobacteria, a chiral UPLC-MS/MS method was developed to separate BMAA enantiomers and isomers and to determine the enantiomeric configuration of endogenous free BMAA in a marine Lyngbya mat and two mussel reference materials. After extraction, purification and derivatization with N-(4-nitrophenoxycarbonyl)-l-phenylalanine 2-methoxyethyl ester ((S)-NIFE), both L- and D-BMAA were identified as free amino acids in cyanobacterial materials, whereas only L-BMAA was identified in mussel tissues. The finding of D-BMAA in biological environmental materials raises questions concerning the source and role of BMAA enantiomers in neurological disease. Full article
(This article belongs to the Special Issue Prospective Studies in Survey and Biosurvey of Cyanotoxins In Situ)
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16 pages, 1627 KiB  
Review
The State-of-the-Art of the Humoral Memory Response to Snakebites: Insights from the Yanomami Population
Toxins 2023, 15(11), 638; https://doi.org/10.3390/toxins15110638 - 01 Nov 2023
Viewed by 1122
Abstract
Snakebite envenomation (SBE)-induced immunity refers to individuals who have been previously bitten by a snake and developed a protective immune response against subsequent envenomations. The notion stems from observations of individuals, including in the indigenous population, who present only mild signs and symptoms [...] Read more.
Snakebite envenomation (SBE)-induced immunity refers to individuals who have been previously bitten by a snake and developed a protective immune response against subsequent envenomations. The notion stems from observations of individuals, including in the indigenous population, who present only mild signs and symptoms after surviving multiple SBEs. Indeed, these observations have engendered scientific interest and prompted inquiries into the potential development of a protective immunity from exposure to snake toxins. This review explores the evidence of a protective immune response developing following SBE. Studies suggest that natural exposure to snake toxins can trigger protection from the severity of SBEs, mediated by specific antibodies. However, the evaluation of the immune memory response in SBE patients remains challenging. Further research is needed to elucidate the immune response dynamics and identify potential targets for therapeutic interventions. Furthermore, the estimation of the effect of previous exposures on SBE epidemiology in hyperendemic areas, such as in the indigenous villages of the Amazon region (e.g., the Yanomami population) is a matter of debate. Full article
(This article belongs to the Section Animal Venoms)
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18 pages, 8575 KiB  
Article
Structural Basis of Clostridium perfringens Enterotoxin Activation and Oligomerization by Trypsin
Toxins 2023, 15(11), 637; https://doi.org/10.3390/toxins15110637 - 31 Oct 2023
Viewed by 1210
Abstract
Clostridium perfringens enterotoxin (CpE) is a β-pore forming toxin that disrupts gastrointestinal homeostasis in mammals by binding membrane protein receptors called claudins. Although structures of CpE fragments bound to claudins have been determined, the mechanisms that trigger CpE activation and oligomerization that lead [...] Read more.
Clostridium perfringens enterotoxin (CpE) is a β-pore forming toxin that disrupts gastrointestinal homeostasis in mammals by binding membrane protein receptors called claudins. Although structures of CpE fragments bound to claudins have been determined, the mechanisms that trigger CpE activation and oligomerization that lead to the formation of cytotoxic β-pores remain undetermined. Proteolysis of CpE in the gut by trypsin has been shown to play a role in this and subsequent cytotoxicity processes. Here, we report solution structures of full-length and trypsinized CpE using small-angle X-ray scattering (SAXS) and crystal structures of trypsinized CpE and its C-terminal claudin-binding domain (cCpE) using X-ray crystallography. Mass spectrometry and SAXS uncover that removal of the CpE N-terminus by trypsin alters the CpE structure to expose areas that are normally unexposed. Crystal structures of trypsinized CpE and cCpE reveal unique dimer interfaces that could serve as oligomerization sites. Moreover, comparisons of these structures to existing ones predict the functional implications of oligomerization in the contexts of cell receptor binding and β-pore formation. This study sheds light on trypsin’s role in altering CpE structure to activate its function via inducing oligomerization on its path toward cytotoxic β-pore formation. Its findings can incite new approaches to inhibit CpE-based cytotoxicity with oligomer-disrupting therapeutics. Full article
(This article belongs to the Special Issue Pore-Forming Toxins from Feature to Function)
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