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Toxins, Volume 17, Issue 2 (February 2025) – 47 articles

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13 pages, 4531 KiB  
Article
Deciphering the Neurotoxic Effects of Karenia selliformis
by Ambbar Aballay-González, Jessica Panes-Fernández, Catharina Alves-de-Souza, Bernd Krock, Juan José Gallardo-Rodríguez, Nicole Espinoza-Rubilar, Jorge Fuentealba and Allisson Astuya-Villalón
Toxins 2025, 17(2), 92; https://doi.org/10.3390/toxins17020092 (registering DOI) - 15 Feb 2025
Abstract
Karenia selliformis is a globally recognized dinoflagellate associated with harmful algal blooms and massive fish kills along southern Chilean coasts. Its toxicity varies with environmental factors and genetic diversity. While K. selliformis is traditionally linked to neurotoxins like gymnodimines (GYMs), analysis of the [...] Read more.
Karenia selliformis is a globally recognized dinoflagellate associated with harmful algal blooms and massive fish kills along southern Chilean coasts. Its toxicity varies with environmental factors and genetic diversity. While K. selliformis is traditionally linked to neurotoxins like gymnodimines (GYMs), analysis of the strain CREAN-KS02 from Chile’s Aysén Region (43° S) revealed no presence of toxins associated with this genus, such as gymnodimines, brevetoxins, or brevenal. Given the high toxicity and impact on marine life, our study aimed to functionally characterize the neurotoxic metabolites in the exudate of K. selliformis cultures. Cytotoxicity was evaluated using a Neuro-2a cell-based assay (CBA), determining an IC50 of 2.41 ± 0.02 μg mL−1. The incubation of Neuro-2a cells with the bioactive lipophilic extract obtained from the exudate of K. selliformis and the ouabain/veratridine couple showed activation of voltage-gated ion channels. Electrophysiological recordings on cultured mouse hippocampal neurons showed that the extract increased cell excitability in a dose-dependent manner, modulating action potential firing and exhibiting an opposed effect to tetrodotoxin. These findings indicate the presence of excitatory neurotoxic compounds affecting mammalian cells. This study provides the first mechanistic evidence of K. selliformis toxicity and highlights potential risks associated with its proliferation in marine environments. Full article
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19 pages, 344 KiB  
Review
The Role of Botulinum Toxin for Masseter Muscle Hypertrophy: A Comprehensive Review
by Martina Ferrillo, Eleonora Sommadossi, Loredana Raciti, Dario Calafiore, Kamal Mezian, Valeria Tarantino, Michele Vecchio, Umile Giuseppe Longo, Luigi Losco and Alessandro de Sire
Toxins 2025, 17(2), 91; https://doi.org/10.3390/toxins17020091 (registering DOI) - 14 Feb 2025
Abstract
Masticatory muscle hypertrophy (MMH) is a rare clinical phenomenon of uncertain etiology, characterized by a soft swelling near the angle of the jaw. This abnormal enlargement of the masseter muscle can alter the facial profile, leading to aesthetic concerns. Moreover, MMH may also [...] Read more.
Masticatory muscle hypertrophy (MMH) is a rare clinical phenomenon of uncertain etiology, characterized by a soft swelling near the angle of the jaw. This abnormal enlargement of the masseter muscle can alter the facial profile, leading to aesthetic concerns. Moreover, MMH may also have significant functional repercussions, including pain in the masseter region, often associated with temporomandibular disorders, fatigue, and discomfort during mastication. Non-conservative approaches offer an effective and minimally invasive solution by inducing localized muscle relaxation and reducing hypertrophy. Botulinum neurotoxin type A (BoNT/A) represents a therapeutic option for managing MMH, considering that injections can effectively reduce the masseter muscle volume, improving both facial aesthetics and related symptoms. Currently, the standard non-surgical management of MMH is BoNT/A injections, although consensus on the average dosage has not been definitely reached; on the other hand, there are data available in the literature about the injection technique of BoNT/A for lower face contouring. Therefore, the present comprehensive review aimed at exploring in detail the role of BoNT/A in the treatment of masseter muscle hypertrophy, describing its mechanism of action, the administration protocols, the clinical effects, and any side effects. Full article
15 pages, 599 KiB  
Article
First Report of Safe Italian Peanut Production Regarding Aflatoxin
by Matteo Crosta, Michele Croci, Chiara Dall’Asta, Michele Pisante and Paola Battilani
Toxins 2025, 17(2), 90; https://doi.org/10.3390/toxins17020090 (registering DOI) - 14 Feb 2025
Abstract
The growing interest in peanut production in Italy represents a significant opportunity from both an agronomic and economic standpoint. Aflatoxin B1 (AFB1) contamination is a major concern with imported peanuts; developing an Italian peanut supply chain can ensure a well-managed local product, [...] Read more.
The growing interest in peanut production in Italy represents a significant opportunity from both an agronomic and economic standpoint. Aflatoxin B1 (AFB1) contamination is a major concern with imported peanuts; developing an Italian peanut supply chain can ensure a well-managed local product, with special care for food safety. This study aimed to provide a first overview of Italian peanut production, focusing on the Aspergillus section Flavi and AFB1 occurrence in the raw product. During 2022 and 2023, 18 peanut fields were sampled at complete maturity across the Italian production areas, considering three varieties: Lotos, SIS-AR_01, and IPG914. The results showed the occurrence of Aspergillus sec. Flavi in peanut pods, even though AFB1 was always absent or in traces, well below the European legal limits. These findings confirmed the quality of Italian peanut production, even though further research is requested to confirm the positive results of this first report. Full article
(This article belongs to the Special Issue Aflatoxins: Contamination, Analysis and Control)
17 pages, 4715 KiB  
Article
Breaking Barriers: Candidalysin Disrupts Epithelial Integrity and Induces Inflammation in a Gut-on-Chip Model
by Moran Morelli and Karla Queiroz
Toxins 2025, 17(2), 89; https://doi.org/10.3390/toxins17020089 - 14 Feb 2025
Abstract
Candida albicans is an opportunistic pathogenic yeast commonly found in the gastrointestinal tract of healthy humans. Under certain conditions, it can become invasive and cause life-threatening systemic infections. One mechanism used by C.albicans to breach the epithelial barrier is the secretion of candidalysin, [...] Read more.
Candida albicans is an opportunistic pathogenic yeast commonly found in the gastrointestinal tract of healthy humans. Under certain conditions, it can become invasive and cause life-threatening systemic infections. One mechanism used by C.albicans to breach the epithelial barrier is the secretion of candidalysin, a cytolytic peptide toxin. Candidalysin damages epithelial membranes and activates the innate immune response, making it key to C.albicans’ pathogenicity and a promising therapeutic target. Although candidalysin mediates C. albicans translocation through intestinal layers, its impact on epithelial responses is not fully understood. This study aims to characterize this response and develop scalable, quantitative methodologies to assess candidalysin’s toxicological effects using gut-on-chip models. We used the OrganoPlate® platform to expose Caco-2 tubules to candidalysin and evaluated their response with trans-epithelial electrical resistance (TEER), protein detection, and immunostaining. We then validated our findings in a proof-of-concept experiment using human intestinal organoid tubules. Candidalysin impaired barrier integrity, induced actin remodeling, and increased cell permeability. It also induced the release of LDH, cytokines, and the antimicrobial peptide LL37, suggesting cellular damage, inflammation, and antimicrobial activity. This study strengthens our understanding of candidalysin’s role in C. albicans pathogenesis and suggests new therapeutic strategies targeting this toxin. Moreover, patient-derived organoids show promise for capturing patient heterogeneity and developing personalized treatments. Full article
(This article belongs to the Special Issue Pore-Forming Toxins: From Structure to Function)
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23 pages, 2230 KiB  
Article
Bothrops jararacussu Venom Inactivated by High Hydrostatic Pressure Enhances the Immunogenicity Response in Horses and Triggers Unexpected Cross-Reactivity with Other Snake Venoms
by Ricardo Teixeira-Araujo, Marisa Carvalho Suarez, Carlos Correa-Netto, Luis Eduardo Ribeiro da Cunha, Debora Foguel and Russolina Benedeta Zingali
Toxins 2025, 17(2), 88; https://doi.org/10.3390/toxins17020088 - 13 Feb 2025
Abstract
High hydrostatic pressure (HHP) has been used for viral inactivation to facilitate vaccine development when immunogenicity is maintained or even increased. In this work, we used HHP to inactivate Bothrops jararacussu venom. Our protocol promotes the loss of or decrease in many biological [...] Read more.
High hydrostatic pressure (HHP) has been used for viral inactivation to facilitate vaccine development when immunogenicity is maintained or even increased. In this work, we used HHP to inactivate Bothrops jararacussu venom. Our protocol promotes the loss of or decrease in many biological activities in venom. Horses were immunized with pressurized venom, and in contrast to native venom, this procedure does not induce any damage to animals. Furthermore, the serum obtained with pressurized venom efficiently neutralized all biological activities of B. jararacussu venom. Antibody titrations were higher in serum produced with pressurized venom compared to that produced by native venom, and this antivenom was not only effective against the venom of B. jararacussu but against the venom of other species and genera. In conclusion, our data show a new technique for producing hyperimmune serum using venom inactivated by HHP, and this method is associated with a reduction in toxic effects in immunized animals and higher potency. Full article
(This article belongs to the Section Animal Venoms)
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18 pages, 3279 KiB  
Review
Rattlesnake Roundup: Point-of-Care Thrombelastographic Methods Define the Molecular Impacts on Coagulation of Crotalus Venom Toxins In Vitro and In Vivo
by Vance G. Nielsen
Toxins 2025, 17(2), 87; https://doi.org/10.3390/toxins17020087 - 13 Feb 2025
Abstract
A malalignment between rattlesnake-envenomed patients’ degree of compromised coagulation and the data generated by standard hematological determinations generated with blood samples anticoagulated with calcium (Ca) chelating agents is almost certain. Many rattlesnake venom toxins are Ca-independent toxins that likely continue to damage plasmatic [...] Read more.
A malalignment between rattlesnake-envenomed patients’ degree of compromised coagulation and the data generated by standard hematological determinations generated with blood samples anticoagulated with calcium (Ca) chelating agents is almost certain. Many rattlesnake venom toxins are Ca-independent toxins that likely continue to damage plasmatic and cellular components of coagulation in blood samples (anticoagulated with Ca chelation) during transportation from the emergency department to the clinical laboratory. The most straightforward approach to abrogate this patient–laboratory malalignment is to reduce “needle to activation time”—the time from blood collection to commencement of laboratory analysis—with utilization of point-of-care (POC) technology such as thrombelastography. The workflow and history of standard and POC approaches to hematological assessment is reviewed. Further, using a preclinical model of envenomation with four different rattlesnake venoms, the remarkably diverse damage to coagulation revealed with POC thrombelastography is presented. It is anticipated that future investigation and potential changes in clinical monitoring practices with POC methods of hematological assessment will improve the management of envenomed patients and assist in precision care. Full article
(This article belongs to the Special Issue Toxins: From the Wild to the Lab)
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25 pages, 2478 KiB  
Article
Thermal Stability and Matrix Binding of Citrinin in the Thermal Processing of Starch-Rich Foods
by Lea Brückner, Florian Neuendorff, Katharina Hadenfeldt, Matthias Behrens, Benedikt Cramer and Hans-Ulrich Humpf
Toxins 2025, 17(2), 86; https://doi.org/10.3390/toxins17020086 - 13 Feb 2025
Abstract
Citrinin (CIT) is a nephrotoxic mycotoxin commonly found in a broad range of foods, including cereals, spices, nuts, or Monascus fermentation products. Analyses have shown that CIT is present in processed foods in significantly lower concentrations than in unprocessed materials. Modified forms of [...] Read more.
Citrinin (CIT) is a nephrotoxic mycotoxin commonly found in a broad range of foods, including cereals, spices, nuts, or Monascus fermentation products. Analyses have shown that CIT is present in processed foods in significantly lower concentrations than in unprocessed materials. Modified forms of CIT arising during food processing may provide an explanation for the discrepancy. This study deals with the thermal stability of CIT and the formation of reaction products of CIT with carbohydrates, followed by toxicological evaluations using cell culture models. HPLC-HRMS degradation curves of CIT heated in different matrix model systems were recorded, and the formation of decarboxycitrinin (DCIT), the main degradation product, was quantified. Additionally, chemical structures of reaction products of CIT with carbohydrates were tentatively identified using MS/MS spectra and stable isotope labelling. Subsequently, the degradation of CIT during biscuit baking was studied, and carbohydrate-bound forms of CIT were detected after enzymatic starch digestion. The formation of DCIT could explain the majority of CIT degradation, but, depending on the process, covalent binding to carbohydrates can also be highly relevant. Cytotoxicity of DCIT in IHKE-cells was found to be lower compared to CIT, while the toxicity as well as the intestinal metabolism of carbohydrate-bound CIT was not evaluated. Full article
(This article belongs to the Section Mycotoxins)
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9 pages, 1642 KiB  
Article
Topography of the Corrugator Supercilii Muscle Relative to the Eyebrow and Its Clinical Application in Botulinum Toxin Injections
by Hyun Jin Shin, You-Jin Choi, Kang-Jae Shin and Wu-Chul Song
Toxins 2025, 17(2), 85; https://doi.org/10.3390/toxins17020085 - 13 Feb 2025
Abstract
The purpose of this study was to elucidate the topography of the corrugator supercilii muscle (CSM) relative to the eyebrow with the aim of providing topographical guidance for botulinum toxin type A (BTX-A) injections in the East Asian population. Thirty-six hemifaces of 18 [...] Read more.
The purpose of this study was to elucidate the topography of the corrugator supercilii muscle (CSM) relative to the eyebrow with the aim of providing topographical guidance for botulinum toxin type A (BTX-A) injections in the East Asian population. Thirty-six hemifaces of 18 donated bodies for anatomical studies were dissected. Prior to dissection, four specific points on the eyebrow were marked to serve as reference points. A superimposition method for analyzing the position of the CSM relative to the eyebrow involved overlaying an image showing the dissected muscle onto a pre-existing image that contained reference lines indicating the eyebrow landmarks. The CSM almost overlaps the eyebrow at its medial end. Significantly, the central part of the CSM’s width was positioned just above the upper point of the eyebrow, being closely aligned with the midpupillary line. There was minimal overlap of the CSM beyond the midpupillary line on the lateral side, indicating that this muscle becomes relatively scarce or less distinct as it extends laterally from the midpupillary line. For effectively targeting the CSM, it is recommended to inject BTX-A precisely at the center of the medial end of the eyebrow just above the midpupillary line. Full article
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17 pages, 5760 KiB  
Article
The Proteolytic Activation, Toxic Effects, and Midgut Histopathology of the Bacillus thuringiensis Cry1Ia Protoxin in Rhynchophorus ferrugineus (Coleoptera: Curculionidae)
by Camilo Ayra-Pardo, Victor Ramaré, Ana Couto, Mariana Almeida, Ricardo Martins, José Américo Sousa and Maria João Santos
Toxins 2025, 17(2), 84; https://doi.org/10.3390/toxins17020084 - 12 Feb 2025
Abstract
The red palm weevil (RPW; Coleoptera: Curculionidae) is a destructive pest affecting palms worldwide, capable of causing significant economic losses and ecological damage in managed palm ecosystems. Current management heavily relies on synthetic insecticides, but their overuse fosters resistance. Bacillus thuringiensis (Bt) offers [...] Read more.
The red palm weevil (RPW; Coleoptera: Curculionidae) is a destructive pest affecting palms worldwide, capable of causing significant economic losses and ecological damage in managed palm ecosystems. Current management heavily relies on synthetic insecticides, but their overuse fosters resistance. Bacillus thuringiensis (Bt) offers a promising alternative, producing toxins selective against various insect orders, including Coleoptera. However, no specific Bt toxin has yet been identified for RPW. This study investigates the toxicity against RPW larvae of the Bt Cry1Ia protoxin, known for its dual activity against Lepidoptera and Coleoptera. A laboratory RPW colony was reared for two generations, ensuring a reliable insect source for bioassays. Cry1Ia was expressed as a 6xHis-tagged fusion protein in Escherichia coli and purified using nickel affinity. Incubation with RPW larval gut proteases for 24 h produced a stable core of ~65 kDa. Diet-incorporation bioassays revealed high Cry1Ia toxicity in neonate larvae. In contrast, the lepidopteran-active Cry1Ac protoxin, used as a robust negative control, was completely degraded after 24 h of in vitro proteolysis and showed no toxicity in bioassays. Cry1Ia-fed larvae exhibited significant midgut cell damage, characteristic of Bt intoxication. These findings highlight Cry1Ia’s strong potential for integration into RPW management programs. Full article
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13 pages, 258 KiB  
Review
Effectiveness of Scolopendrid Pharmacopuncture for Neuropathic Dysfunction: Clinical Evidence and Potential Mechanism
by Jung-Hyun Kim, Tae-Yoon Kim, Bonhyuk Goo and Sang-Soo Nam
Toxins 2025, 17(2), 83; https://doi.org/10.3390/toxins17020083 - 12 Feb 2025
Abstract
Animal venoms, particularly Scolopendrid venom, have gained significant attention as therapeutic agents in complementary and alternative medicine, especially for applications in pain management and neuroprotection. In traditional Korean medicine, Scolopendrid venom is administered through pharmacopuncture, a method that combines injection therapy with principals [...] Read more.
Animal venoms, particularly Scolopendrid venom, have gained significant attention as therapeutic agents in complementary and alternative medicine, especially for applications in pain management and neuroprotection. In traditional Korean medicine, Scolopendrid venom is administered through pharmacopuncture, a method that combines injection therapy with principals of acupuncture. The present review focuses on the multifaceted effects of Scolopendrid pharmacopuncture, derived from Scolopendra polymorpha, on the peripheral nervous system, and its potential role in addressing the neuropathic dysfunction that often arises from peripheral nerve injuries. Scolopendrid venom exhibits various pharmacological properties, including analgesic, anti-inflammatory, and neuroprotective effects. Experimental studies have shown that Scolopendrid pharmacopuncture significantly reduces neuropathic pain in animal models by modulating ion channels and inflammatory pathways. Clinical investigations have further revealed its efficacy in alleviating pain associated with conditions such as Bell’s palsy and carpal tunnel syndrome. Despite its promising therapeutic potential, the lack of comprehensive clinical research on the toxicity and safety profiles of SPP remains a critical limitation. Future studies should focus on evaluating the safety of Scolopendrid venom as a standalone treatment and incorporate broader data sources to enhance our understanding of its implications in clinical practice. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
19 pages, 2603 KiB  
Article
Innovative Mycotoxin Detoxifying Agents Decrease the Absorption Rate of Aflatoxin B1 and Counteract the Oxidative Stress in Broiler Chickens Exposed to Low Dietary Levels of the Mycotoxin
by Matteo Cuccato, Neenu Amminikutty, Veronica Spalenza, Vanessa Conte, Stefano Bagatella, Donato Greco, Vito D’Ascanio, Francesco Gai, Achille Schiavone, Giuseppina Avantaggiato, Carlo Nebbia and Flavia Girolami
Toxins 2025, 17(2), 82; https://doi.org/10.3390/toxins17020082 - 10 Feb 2025
Abstract
Aflatoxin B1 (AFB1) can impair the growth of chickens and reduce the quality of eggs and meat, resulting in significant economic losses. The inclusion of mycotoxin detoxifying agents (MyDA) with binding properties in the diet is an efficient tool to reduce their absorption [...] Read more.
Aflatoxin B1 (AFB1) can impair the growth of chickens and reduce the quality of eggs and meat, resulting in significant economic losses. The inclusion of mycotoxin detoxifying agents (MyDA) with binding properties in the diet is an efficient tool to reduce their absorption rate in the gastrointestinal tract. Our aim was to investigate the ability of two innovative MyDA (SeOX, a feed additive featuring a tri-octahedral smectite mixed with lignocellulose, and CHS, a di-octahedral smectite functionalized with an organic non-toxic modifier) in both reducing the bio-accessibility and mitigating the adverse effects of AFB1 in broilers exposed for 10 days to concentrations approaching the European Union maximum limits in feed (0.02 mg/kg). The amount of AFB1 in the excreta of birds, collected over four consecutive days (starting on day 7), was significantly lower (p < 0.001) in the group exposed to AFB1 alone compared to the groups treated with either SeOX or CHS. The calculated bio-accessibility was decreased by nearly 30% with both MyDA. This positive effect was reflected by a significant reduction (p < 0.001) in the oxidative stress (measured as serum antioxidant capacity and hepatic lipid peroxidation) induced by AFB1. Although antioxidant enzyme activities and glutathione levels were unaffected by any treatment, AFB1 significantly induced (p < 0.001) the upregulation of CYP2A6 and the downregulation of Nrf2; the latter was reverted by each MyDA. Overall, these results demonstrate that the selected MyDA are effective in limiting the AFB1 absorption rate, thereby mitigating or even reverting the oxidative stress induced by AFB1 in broilers. Full article
(This article belongs to the Special Issue Aspergillus flavus and Aflatoxins (Volume III))
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22 pages, 5060 KiB  
Article
Phylogenetic and Autecology Characteristics of Five Potentially Harmful Dinoflagellate Alexandrium Species (Dinophyceae, Gonyaulacales, Pyrocystaceae) in Tropical Waters: A. affine, A. fraterculus, A. leei, A. pseudogonyaulax, and A. tamiyavanichii
by Lam Nguyen-Ngoc, Dang-Minh Luat, H. Doan-Nhu, H. M. Pham, B. Krock, N. D. Huynh-Thi, L. V. Tran-Thi, M. H. Tran-Thi, Anh H. Pham, V. Nguyen-Tam, T. T. Nhan-Luu and H. H. Do
Toxins 2025, 17(2), 81; https://doi.org/10.3390/toxins17020081 - 10 Feb 2025
Abstract
Five species of Alexandrium (A. affine, A. fraterculus, A. leei, A. pseudogonyaulax, and A. tamiyavanichii) are commonly found in Vietnamese waters. They were distinguished based on their apical pore complex (A.P.C), precingular first plate [...] Read more.
Five species of Alexandrium (A. affine, A. fraterculus, A. leei, A. pseudogonyaulax, and A. tamiyavanichii) are commonly found in Vietnamese waters. They were distinguished based on their apical pore complex (A.P.C), precingular first plate (1′), ventral pore (Vp), and sulcal platelets. A genetic analysis was conducted using nuclear rDNA sequences of ITS and LSU (D1–D3, D8–D10). The growth rates of A. fraterculus, A. leei, A. tamiyavanichii, and A. pseudogonyaulax were quite similar. Specifically, these four species had the highest growth rates at two temperature levels of 24 °C and 27 °C, at salinities ranging from 25 psu to 35 psu. Furthermore, these species were able to adapt to a low salinity of 20 psu at temperatures from 18 °C to 27 °C. No Paralytic Shellfish Toxins (PSTs) were found in the two Alexandrium affine strains, VINVN01-1 and VINVN01-2. The detection limit for PSTs ranged from 0.45 to 15.5 fg cell−1, depending on the molecular response and available biomass. Full article
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17 pages, 2525 KiB  
Article
Effects of Dinoflagellate Toxins Okadaic Acid and Dinophysistoxin-1 and -2 on the Microcrustacean Artemia franciscana
by Federica Cavion, Silvio Sosa, Jane Kilcoyne, Alessandra D’Arelli, Cristina Ponti, Michela Carlin, Aurelia Tubaro and Marco Pelin
Toxins 2025, 17(2), 80; https://doi.org/10.3390/toxins17020080 - 10 Feb 2025
Abstract
Harmful algal blooms are an expanding phenomenon negatively impacting human health, socio-economic welfare, and ecosystems. Such events increase the risk of marine organisms’ exposure to algal toxins with consequent ecological effects. In this frame, the objective of this study was to investigate the [...] Read more.
Harmful algal blooms are an expanding phenomenon negatively impacting human health, socio-economic welfare, and ecosystems. Such events increase the risk of marine organisms’ exposure to algal toxins with consequent ecological effects. In this frame, the objective of this study was to investigate the ecotoxicological potential of three globally distributed dinoflagellate toxins (okadaic acid, OA; dinophysistoxin-1, DTX-1; dinophysistoxin-2, DTX-2) using Artemia franciscana as a model organism of marine zooplankton. Each toxin (0.1–100 nM) was evaluated for its toxic effects in terms of cyst hatching, mortality of nauplii Instar I and adults, and biochemical responses related to oxidative stress. At the highest concentration (100 nM), these toxins significantly increased adults’ mortality starting from 24 h (DTX-1), 48 h (OA), or 72 h (DTX-2) exposures, DTX-1 being the most potent one, followed by OA and DTX-2. The quantitation of oxidative stress biomarkers in adults, i.e., reactive oxygen species (ROS) production and activity of three endogenous antioxidant defense enzymes (glutathione S-transferase, superoxide dismutase, and catalase) showed that only DTX-2 significantly increased ROS production, whereas each toxin affected the antioxidant enzymes with a different activity profile. In general, the results indicate a negative impact of these toxins towards A. franciscana with potential consequences on the marine ecosystem. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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29 pages, 7628 KiB  
Review
Fifty Years of Aflatoxin Research in Qidong, China: A Celebration of Team Science to Improve Public Health
by Jian-Guo Chen, Yuan-Rong Zhu, Geng-Sun Qian, Jin-Bing Wang, Jian-Hua Lu, Thomas W. Kensler, Lisa P. Jacobson, Alvaro Muñoz and John D. Groopman
Toxins 2025, 17(2), 79; https://doi.org/10.3390/toxins17020079 - 9 Feb 2025
Abstract
The Qidong Liver Cancer Institute (QDLCI) and the Qidong Cancer Registry were established in 1972 with input from doctors, other medical practitioners, and non-medical investigators arriving from urban centers such as Shanghai and Nanjing. Medical teams were established to quantify the extent of [...] Read more.
The Qidong Liver Cancer Institute (QDLCI) and the Qidong Cancer Registry were established in 1972 with input from doctors, other medical practitioners, and non-medical investigators arriving from urban centers such as Shanghai and Nanjing. Medical teams were established to quantify the extent of primary liver cancer in Qidong, a corn-growing peninsula on the north side of the Yangtze River. High rates of liver cancer were documented and linked to several etiologic agents, including aflatoxins. Local corn, the primary dietary staple, was found to be consistently contaminated with high levels of aflatoxins, and bioassays using this corn established its carcinogenicity in ducks and rats. Observational studies noted a positive association between levels of aflatoxin in corn and incidence of liver cancer across townships. Biomarker studies measuring aflatoxin B1 and its metabolite aflatoxin M1 in biofluids reflected the exposures. Approaches to decontamination of corn from aflatoxins were also studied. In 1993, investigators from Johns Hopkins University were invited to visit the QDLCI to discuss chemoprevention studies in some townships. A series of placebo-controlled clinical trials were conducted using oltipraz (a repurposed drug), chlorophyllin (an over-the-counter drug), and beverages prepared from 3-day-old broccoli sprouts (rich in the precursor phytochemical for sulforaphane). Modulation of biomarkers of aflatoxin DNA and albumin adducts established proof of principle for the efficacy of these agents in enhancing aflatoxin detoxication. Serendipitously, by 2012, aflatoxin exposures quantified using biomarker measurements documented a many hundred-fold reduction. In turn, the Cancer Registry documents that the age-standardized incidence rate of liver cancer is now 75% lower than that seen in the 1970s. This reduction is seen in Qidongese who have never received the hepatitis B vaccination. Aflatoxin mitigation driven by economic changes switched the dietary staple of contaminated corn to rice coupled with subsequent dietary diversity leading to lower aflatoxin exposures. This 50-year effort to understand the etiology of liver cancer in Qidong provides the strongest evidence for aflatoxin mitigation as a public health strategy for reducing liver cancer burden in exposed, high-risk populations. Also highlighted are the challenges and successes of international team science to solve pressing public health issues. Full article
(This article belongs to the Section Mycotoxins)
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34 pages, 1404 KiB  
Review
Conotoxins: Classification, Prediction, and Future Directions in Bioinformatics
by Rui Li, Junwen Yu, Dongxin Ye, Shanghua Liu, Hongqi Zhang, Hao Lin, Juan Feng and Kejun Deng
Toxins 2025, 17(2), 78; https://doi.org/10.3390/toxins17020078 - 9 Feb 2025
Abstract
Conotoxins, a diverse family of disulfide-rich peptides derived from the venom of Conus species, have gained prominence in biomedical research due to their highly specific interactions with ion channels, receptors, and neurotransmitter systems. Their pharmacological properties make them valuable molecular tools and promising [...] Read more.
Conotoxins, a diverse family of disulfide-rich peptides derived from the venom of Conus species, have gained prominence in biomedical research due to their highly specific interactions with ion channels, receptors, and neurotransmitter systems. Their pharmacological properties make them valuable molecular tools and promising candidates for therapeutic development. However, traditional conotoxin classification and functional characterization remain labor-intensive, necessitating the increasing adoption of computational approaches. In particular, machine learning (ML) techniques have facilitated advancements in sequence-based classification, functional prediction, and de novo peptide design. This review explores recent progress in applying ML and deep learning (DL) to conotoxin research, comparing key databases, feature extraction techniques, and classification models. Additionally, we discuss future research directions, emphasizing the integration of multimodal data and the refinement of predictive frameworks to enhance therapeutic discovery. Full article
(This article belongs to the Special Issue Conotoxins: Evolution, Classifications and Targets)
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18 pages, 4261 KiB  
Article
Investigating the Correlations Between Weather Factors and Mycotoxin Contamination in Corn: Evidence from Long-Term Data
by Alexander Platzer, Younos Cherkaoui, Barbara Novak and Gerd Schatzmayr
Toxins 2025, 17(2), 77; https://doi.org/10.3390/toxins17020077 - 8 Feb 2025
Abstract
Mycotoxins are secondary metabolites produced by certain fungi, posing significant health risks to humans and animals through contaminated food and feed. These fungi, and consequently the mycotoxins which they produce, are strongly influenced by weather, and this shifts over time due to climate [...] Read more.
Mycotoxins are secondary metabolites produced by certain fungi, posing significant health risks to humans and animals through contaminated food and feed. These fungi, and consequently the mycotoxins which they produce, are strongly influenced by weather, and this shifts over time due to climate change, leading to more frequent and severe events, such as heat waves, storms, and heavy rainfall. This study investigates how long-term weather trends and climatic factors impacted mycotoxin levels in corn samples over a 17-year period (2006–2022) across 12 countries, with a focus on 136 specific weather features. Among all potential relationships, we found Aspergillus toxins and fumonisins to be positively correlated with temperature, while deoxynivalenol and zearalenone are negatively correlated. Additionally, the dew point, particularly its 90th percentile value, is positively correlated with Aspergillus mycotoxins. We also identified significant patterns associated with wind direction. Collectively, these findings offer a comprehensive overview of mycotoxin–weather correlations, which may also be projected into future scenarios. Full article
(This article belongs to the Collection Impact of Climate Change on Fungal Population and Mycotoxins)
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31 pages, 1310 KiB  
Systematic Review
An Update of Tetrodotoxins Toxicity and Risk Assessment Associated to Contaminated Seafood Consumption in Europe: A Systematic Review
by Carlo Varini, Maura Manganelli, Simona Scardala, Pietro Antonelli, Carmen Losasso and Emanuela Testai
Toxins 2025, 17(2), 76; https://doi.org/10.3390/toxins17020076 - 8 Feb 2025
Abstract
Following the occurrence of Tetrodotoxins (TTXs) in Europe—a group of neurotoxins identified in Asia, where fatalities occurred after the ingestion of contaminated pufferfish—the EFSA proposed a limit of 44 µg of TTX/kg of shellfish meat in mollusks in 2017, to protect heavy consumers. [...] Read more.
Following the occurrence of Tetrodotoxins (TTXs) in Europe—a group of neurotoxins identified in Asia, where fatalities occurred after the ingestion of contaminated pufferfish—the EFSA proposed a limit of 44 µg of TTX/kg of shellfish meat in mollusks in 2017, to protect heavy consumers. The limit was based on an acute reference dose (ARfD) derived from the few available data on TTX toxicity. TTX is expected to increase with sea-surface warming; indeed, it has been found in spring/summer in mollusks in Europe, with concentrations often exceeding this limit. Due to the numerous uncertainties of the EFSA’s ARfD, we conducted a systematic review to provide an update on TTX toxicity. Out of 12,741 articles retrieved from PubMed, Science Direct, and Scopus since 2017, only 17 were eligible for data extraction. Our results show that they are not sufficient to modify the EFSA’s conclusions. Furthermore, our analysis of occurrence data in European seafood, to assess the current risk of exposure to TTX, reveals several gaps, such as different LODs/LOQs and seasonal monitoring not allowing comparisons between areas and too few analyzed sites. However, the presence of positive samples exceeding the EFSA limit indicates a potential risk even for general consumers, highlighting the urgency to address these knowledge gaps. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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14 pages, 1690 KiB  
Article
Metabolomic Profiling of Human Urine Related to Mycotoxin Exposure
by Nuria Dasí-Navarro, Sonia Lombardi, Pilar Vila-Donat, Sabrina Llop, Jesus Vioque, Raquel Soler-Blasco, Ana Esplugues, Lara Manyes and Manuel Lozano
Toxins 2025, 17(2), 75; https://doi.org/10.3390/toxins17020075 - 8 Feb 2025
Abstract
Human exposure to mycotoxins is a global concern since several mycotoxins, such as enniatins and aflatoxins, have shown carcinogenic and neurotoxic effects, and the toxicologic mechanisms of most of them still need to be clarified. This study aims to investigate the metabolic pathways [...] Read more.
Human exposure to mycotoxins is a global concern since several mycotoxins, such as enniatins and aflatoxins, have shown carcinogenic and neurotoxic effects, and the toxicologic mechanisms of most of them still need to be clarified. This study aims to investigate the metabolic pathways affected by mycotoxin exposure by evaluating metabolite alterations in urine. The participants were 540 women from the Spanish Childhood and Environment Project (INMA). For metabolite identification, a dilute and shoot extraction, followed by HPLC-Q-TOF-MS identification analysis, was performed. Data were processed using Agilent Mass Hunter Workstation with the METLIN database, Agilent Mass Profiler Professional 10.0, and Metaboanalyst 6.0. Over 2000 metabolites were obtained in each sample after feature extraction, and the most significant metabolites (p-value ≤ 0.05, fold change ≥ 2.0) were considered for pathway analysis. Enrichment analysis and topology showed that the most significantly affected pathway was the biosynthesis of unsaturated fatty acids (adjusted p-value = 0.007), with four metabolomic hits associated: linoleic acid, octadecanoic acid/stearic acid, an arachidonic acid metabolite, and (9Z)-octadecenoic acid/oleic acid. Other related pathways (unadjusted p-value ≤ 0.1) included fatty acid biosynthesis, glycerophospholipid metabolism, and ether lipid metabolism. The present study highlights the importance of metabolomics in increasing knowledge of the toxicity mechanisms and health effects of mycotoxins, especially emerging ones. Full article
(This article belongs to the Section Mycotoxins)
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13 pages, 1396 KiB  
Article
Detection of Ochratoxin A in Tissues of Wild Boars (Sus scrofa) from Southern Italy
by Sara Damiano, Consiglia Longobardi, Lucia De Marchi, Nadia Piscopo, Valentina Meucci, Alessio Lenzi and Roberto Ciarcia
Toxins 2025, 17(2), 74; https://doi.org/10.3390/toxins17020074 - 6 Feb 2025
Abstract
Ochratoxin A (OTA) is a secondary metabolite produced by fungi of the genera Aspergillus and Penicillium, known to contaminate various food substrates. Its toxic effects include direct nephrotoxicity, as well as observed teratogenic, immunogenic, and carcinogenic effects. Climate change may contribute to [...] Read more.
Ochratoxin A (OTA) is a secondary metabolite produced by fungi of the genera Aspergillus and Penicillium, known to contaminate various food substrates. Its toxic effects include direct nephrotoxicity, as well as observed teratogenic, immunogenic, and carcinogenic effects. Climate change may contribute to increased humidity and temperature, favouring fungal growth and, consequently, OTA spreading. Recent increases in wild boar populations, along with their omnivorous nature and their varied diet, define them as environmental bioindicators for contaminants like mycotoxins. This study aimed to assess the concentrations of OTA in kidney, liver, and muscle tissue samples from 74 wild boars that were hunted in different areas of Avellino, Campania region, between 2021 and 2022. Tissue samples underwent extraction, purification, and analysis using high-performance liquid chromatography (HPLC) coupled with a fluorescence detector. Results revealed OTA presence in 35.1% of tested wild boars. The highest OTA concentration was observed in the kidney and liver, with less in the muscle, indicating the presence of this mycotoxin in the wild boars and their surrounding environment. Consequently, there is a need to formulate rules for edible wildlife products. These findings emphasize the significant risk of OTA contamination in wild boar tissues, suggesting their potential as reliable environmental markers for mycotoxin prevalence and as a toxicological concern for human health. Full article
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20 pages, 10727 KiB  
Article
α-Latrotoxin Actions in the Absence of Extracellular Ca2+ Require Release of Stored Ca2+
by Jennifer K. Blackburn, Quazi Sufia Islam, Ouafa Benlaouer, Svetlana A. Tonevitskaya, Evelina Petitto and Yuri A. Ushkaryov
Toxins 2025, 17(2), 73; https://doi.org/10.3390/toxins17020073 - 6 Feb 2025
Abstract
α-Latrotoxin (αLTX) causes exhaustive release of neurotransmitters from nerve terminals in the absence of extracellular Ca2+ (Ca2+e). To investigate the mechanisms underlying this effect, we loaded mouse neuromuscular junctions with BAPTA-AM. This membrane-permeable Ca2+-chelator demonstrates that Ca [...] Read more.
α-Latrotoxin (αLTX) causes exhaustive release of neurotransmitters from nerve terminals in the absence of extracellular Ca2+ (Ca2+e). To investigate the mechanisms underlying this effect, we loaded mouse neuromuscular junctions with BAPTA-AM. This membrane-permeable Ca2+-chelator demonstrates that Ca2+e-independent effects of αLTX require an increase in cytosolic Ca2+ (Ca2+cyt). We also show that thapsigargin, which depletes Ca2+ stores, induces neurotransmitter release, but inhibits the effect of αLTX. We then studied αLTX’s effects on Ca2+cyt using neuroblastoma cells expressing signaling-capable or signaling-incapable variants of latrophilin-1, a G protein-coupled receptor of αLTX. Our results demonstrate that αLTX acts as a cation ionophore and a latrophilin agonist. In model cells at 0 Ca2+e, αLTX forms membrane pores and allows the influx of Na+; this reverses the Na+-Ca2+ exchanger, leading to the release of stored Ca2+ and inhibition of its extrusion. Concurrently, αLTX stimulates latrophilin signaling, which depletes a Ca2+ store and induces transient opening of Ca2+ channels in the plasmalemma that are sensitive to inhibitors of store-operated Ca2+ entry. These results indicate that Ca2+ release from intracellular stores and that Ca2+ influx through latrophilin-activated store-operated Ca2+ channels contributes to αLTX actions and may be involved in physiological control of neurotransmitter release at nerve terminals. Full article
(This article belongs to the Special Issue Animal Venoms: Unraveling the Molecular Complexity (2nd Edition))
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20 pages, 6662 KiB  
Article
Pore-Forming Protein LIN-24 Enhances Starvation Resilience in Caenorhabditis elegans by Modulating Lipid Metabolism and Mitochondrial Dynamics
by Xinqiang Lan, Mengqi Yang, Jiali Wang, Chunping Huang, Andong Wu, Leilei Cui, Yingqi Guo, Lin Zeng, Xiaolong Guo, Yun Zhang, Yang Xiang and Qiquan Wang
Toxins 2025, 17(2), 72; https://doi.org/10.3390/toxins17020072 - 6 Feb 2025
Abstract
The ability to survive starvation is a critical evolutionary adaptation, yet the molecular mechanisms underlying this capability remain incompletely understood. Pore-forming proteins (PFPs) are typically associated with immune defense, where they disturb the membranes of target cells. However, the role of PFPs in [...] Read more.
The ability to survive starvation is a critical evolutionary adaptation, yet the molecular mechanisms underlying this capability remain incompletely understood. Pore-forming proteins (PFPs) are typically associated with immune defense, where they disturb the membranes of target cells. However, the role of PFPs in non-immune functions, particularly in metabolic and structural adaptations to starvation, is less explored. Here, we investigate the aerolysin-like PFP LIN-24 in Caenorhabditis elegans and uncover its novel function in enhancing starvation resistance. We found that LIN-24 expression is upregulated during starvation, leading to increased expression of the lipase-encoding gene lipl-3. This upregulation accelerates the mobilization and degradation of lipid stores, thereby sustaining energy levels. Additionally, LIN-24 overexpression significantly preserves muscle integrity, as evidenced by the maintenance of muscle structure compared to wild-type worms. Furthermore, we demonstrate that LIN-24 induces the formation of donut-shaped mitochondria, a structural change likely aimed at reducing ATP production to conserve energy during prolonged nutrient deprivation. This mitochondrial remodeling depends on genes involved in mitochondrial dynamics, including mff-1, mff-2, drp-1, and clk-1. Collectively, these findings expand our understanding of PFPs, demonstrating their multifaceted role in stress resistance beyond immune defense. LIN-24’s involvement in regulating metabolism, preserving muscle structure, and remodeling mitochondria highlights its crucial role in the adaptive response to starvation, offering novel insights into the evolution of stress resistance mechanisms and potential therapeutic targets for conditions related to muscle preservation and metabolic regulation. Full article
(This article belongs to the Special Issue Pore-Forming Toxins: From Structure to Function)
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29 pages, 2015 KiB  
Review
Targeting Enterotoxins: Advancing Vaccine Development for Enterotoxigenic Escherichia coli ETEC
by Josune Salvador-Erro, Yadira Pastor and Carlos Gamazo
Toxins 2025, 17(2), 71; https://doi.org/10.3390/toxins17020071 - 6 Feb 2025
Abstract
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal disease worldwide, particularly in children in low- and middle-income countries. Its ability to rapidly colonize the intestinal tract through diverse colonization factors and toxins underpins its significant public health impact. Despite extensive research [...] Read more.
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal disease worldwide, particularly in children in low- and middle-income countries. Its ability to rapidly colonize the intestinal tract through diverse colonization factors and toxins underpins its significant public health impact. Despite extensive research and several vaccine candidates reaching clinical trials, no licensed vaccine exists for ETEC. This review explores the temporal and spatial coordination of ETEC virulence factors, focusing on the interplay between adherence mechanisms and toxin production as critical targets for therapeutic intervention. Advancements in molecular biology and host–pathogen interaction studies have uncovered species-specific variations and cross-reactivity between human and animal strains. In particular, the heat-labile (LT) and heat-stable (ST) toxins have provided crucial insights into molecular mechanisms and intestinal disruption. Additional exotoxins, such as EAST-1 and hemolysins, further highlight the multifactorial nature of ETEC pathogenicity. Innovative vaccine strategies, including multiepitope fusion antigens (MEFAs), mRNA-based approaches, and glycoconjugates, aim to enhance broad-spectrum immunity. Novel delivery methods, like intradermal immunization, show promise in eliciting robust immune responses. Successful vaccination against ETEC will offer an effective and affordable solution with the potential to greatly reduce mortality and prevent stunting, representing a highly impactful and cost-efficient solution to a critical global health challenge. Full article
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21 pages, 3710 KiB  
Review
Brown Spider Venom Phospholipases D: From Potent Molecules Involved in Pathogenesis of Brown Spider Bites to Molecular Tools for Studying Ectosomes, Ectocytosis, and Its Applications
by Ana Carolina Martins Wille, Mariana Izabele Machado, Samira Hajjar Souza, Hanna Câmara da Justa, Maria Eduarda de Fraga-Ferreira, Eloise de Souza Mello, Luiza Helena Gremski and Silvio Sanches Veiga
Toxins 2025, 17(2), 70; https://doi.org/10.3390/toxins17020070 - 5 Feb 2025
Abstract
Accidents caused by Loxosceles spiders, commonly known as brown spiders, are frequent in warm and temperate regions worldwide, with a higher prevalence in South America and the southern United States. In the venoms of species clinically associated with accidents, phospholipases D (PLDs) are [...] Read more.
Accidents caused by Loxosceles spiders, commonly known as brown spiders, are frequent in warm and temperate regions worldwide, with a higher prevalence in South America and the southern United States. In the venoms of species clinically associated with accidents, phospholipases D (PLDs) are the most expressed toxins. This classification is based on the toxins’ ability to cleave various phospholipids, with a preference for sphingomyelin. Studies using purified PLDs have demonstrated that these enzymes cleave phospholipids from cells, producing derivatives that can activate leukocytes. A dysregulated inflammatory response is the primary effect following envenomation, leading to dermonecrosis, which is histopathologically characterized by aseptic coagulative necrosis—a key feature of envenomation. Although advances in understanding the structure–function relationship of enzymes have been achieved through molecular biology, heterologous expression, site-directed mutations, crystallography, and bioinformatic analyses—describing PLDs in the venoms of various species and highlighting the conservation of amino acid residues involved in catalysis, substrate binding, and magnesium stabilization—little is known about the cellular biology of these PLDs. Studies have shown that the treatment of various cells with recombinant PLDs stimulates the formation of ectosomes and ectocytosis, events that initiate a cascade of intracellular signaling in PLD-binding cells and lead to the release of extracellular microvesicles. These microvesicles may act as signalosomes for other target cells, thereby triggering an inflammatory response and dermonecrosis. In this review, we will discuss the biochemical properties of PLDs, the target cells that bind to them, and the ectocytosis-dependent pathophysiology of envenoming. Full article
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23 pages, 2779 KiB  
Article
Biomarkers of Fumonisin Exposure in Pigs Fed the Maximum Recommended Level in Europe
by Elodie Lassallette, Alix Pierron, Didier Tardieu, Solène Reymondaud, Marie Gallissot, Maria Angeles Rodriguez, Pi Nyvall Collén, Olivier Roy and Philippe Guerre
Toxins 2025, 17(2), 69; https://doi.org/10.3390/toxins17020069 - 4 Feb 2025
Abstract
This study investigated biomarkers of fumonisin exposure in pigs fed diets contaminated with fumonisins at the European Union’s maximum recommended level. Pigs were assigned to either a fumonisin (FB) diet or a fumonisin plus AlgoClay (FB + AC) diet for durations of 4, [...] Read more.
This study investigated biomarkers of fumonisin exposure in pigs fed diets contaminated with fumonisins at the European Union’s maximum recommended level. Pigs were assigned to either a fumonisin (FB) diet or a fumonisin plus AlgoClay (FB + AC) diet for durations of 4, 9, and 14 days. At 14 days, the plasma Sa1P:So1P ratio increased in pigs fed the FB diet, while the Sa:So ratio remained unchanged. In the liver, FB1 was detected at four days of exposure, with the concentration tending to increase through day 14. The Sa:So and C22-24:C16 ratios of 18:1-, 18:2-, and m18:1-ceramides were elevated at 9 and 14 days, respectively. In the kidneys, FB1 was only detectable at 14 days, and the Sa:So and C22-24:C16 ratios of 18:1-ceramides were increased. In both the liver and kidneys, the increase in the C22-24:C16 ratio was attributed to a reduction of C16 ceramides. In the lungs, no FB1 was detected; however, the Sa:So and Sa1P:So1P ratios increased, and C16 ceramide concentrations decreased at 14 days. Feeding the pigs the FB + AC diet resulted in a reduction of the FB1 tissue-to-feed ratio in the liver and kidneys but did not affect the Sa:So or Sa1P:So1P ratios. Interestingly, the decreases in C16 ceramides observed in the FB diet group were no longer detectable in the FB + AC group. Overall, these findings highlight the complexity of the relationship between FB1 tissue concentrations and sphingolipid changes, suggesting that a comprehensive analysis of multiple biomarkers is required to fully understand fumonisin’s effects. Full article
(This article belongs to the Special Issue Mycotoxins Exposure and Impact on Human and Animal Health)
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20 pages, 2975 KiB  
Article
Biocontrol Activity of New Lactic Acid Bacteria Isolates Against Fusaria and Fusarium Mycotoxins
by S. Vipin Krishnan, P. A. Anaswara, K. Madhavan Nampoothiri, Szilvia Kovács, Cintia Adácsi, Pál Szarvas, Szabina Király, István Pócsi and Tünde Pusztahelyi
Toxins 2025, 17(2), 68; https://doi.org/10.3390/toxins17020068 - 4 Feb 2025
Abstract
As significant fungal pathogens of crops, Fusaria species contaminate various food and feed commodities. Some of the Fusarium spp. secondary metabolites (e.g., trichothecenes, zearalenone, and fumonisins) are widely known toxic molecules (mycotoxins) with chronic and acute effects on humans and animals. The growing [...] Read more.
As significant fungal pathogens of crops, Fusaria species contaminate various food and feed commodities. Some of the Fusarium spp. secondary metabolites (e.g., trichothecenes, zearalenone, and fumonisins) are widely known toxic molecules (mycotoxins) with chronic and acute effects on humans and animals. The growing demand for safer, pesticide-free food drives us to increase biological control during crop growing. Recent research suggests that lactic acid bacteria (LABs) as biocontrol are the best choice for extenuating Fusarium mycotoxins. Newly isolated LABs were tested as antifungal agents against Fusarium verticillioides, F. graminearum, and F. oxysporum. The characterized and genetically identified LABs belonged to Limosilactobacillus fermentum (SD4) and Lactiplantibacillus plantarum (FCW4 and CB2) species. All tested LABs and their cell-free culture supernatants showed antagonism on the MRS solid medium. The antifungal activity was also demonstrated on surface-sterilized wheat and peanuts. The germination test of corn kernels proved that the LAB strains SD4 and FCW4 significantly (p < 0.05) enhanced root and shoot development in plantlets while simultaneously suppressing the outgrowth of F. verticillioides. Small-scale corn silage fermentation revealed the significant effects of SD4 supplementation (decreased zearalenone, lower mold count, and total reduction of deoxynivalenol) within the mixed populations. Full article
(This article belongs to the Special Issue Mitigation and Detoxification Strategies of Mycotoxins)
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16 pages, 2376 KiB  
Article
Distinct Impact of Processing on Cross-Order Cry1I Insecticidal Activity
by Dafne Toledo, Yolanda Bel, Stefanie Menezes de Moura, Juan Luis Jurat-Fuentes, Maria Fatima Grossi de Sa, Aida Robles-Fort and Baltasar Escriche
Toxins 2025, 17(2), 67; https://doi.org/10.3390/toxins17020067 - 3 Feb 2025
Abstract
The insecticidal Cry proteins from Bacillus thuringiensis are used in biopesticides or transgenic crops for pest control. The Cry1I protein family has unique characteristics of being produced during the vegetative rather than sporulation phase, its protoxins forming dimers in solution, and exhibiting dual [...] Read more.
The insecticidal Cry proteins from Bacillus thuringiensis are used in biopesticides or transgenic crops for pest control. The Cry1I protein family has unique characteristics of being produced during the vegetative rather than sporulation phase, its protoxins forming dimers in solution, and exhibiting dual toxicity against lepidopteran and coleopteran pests. The Cry1Ia protoxin undergoes sequential proteolysis from the N- and C-terminal ends, producing intermediate forms with insecticidal activity, while in some cases, the fully processed toxin is inactive. We investigated the oligomerization and toxicity of Cry1Ia intermediate forms generated through trypsinization (T-Int) and larval gut fluid (GF-Int) treatments, as well as the fully trypsinized protein (toxin). Heterologously expressed intermediate forms assembled into oligomers and showed similar toxicity to Cry1Ia protoxin against Ostrinia nubilalis (European corn borer) larvae, while the toxin form was ~30 times less toxic. In contrast, bioassays with Leptinotarsa decemlineata (Colorado potato beetle) larvae did not show significant differences in toxicity among Cry1Ia protoxin, T-Int, GF-Int, and fully processed toxin. These results suggest that the Cry1I mode of action differs by insect order, with N-terminal cleavage affecting toxicity against lepidopteran but not coleopteran larvae. This knowledge is essential for designing pest control strategies using Cry1I insecticidal proteins. Full article
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20 pages, 3095 KiB  
Article
The Anthelmintic Activity of Stonefish (Synanceia spp.) Ichthyocrinotoxins and Their Potential as Novel Therapeutics
by Danica Lennox-Bulow, Jamie Seymour, Alex Loukas and Michael Smout
Toxins 2025, 17(2), 66; https://doi.org/10.3390/toxins17020066 - 2 Feb 2025
Abstract
Parasitic gastrointestinal worms (i.e., helminths) remain a significant global health and economic burden. The increasing inefficacy of current anthelmintic drugs against parasitic diseases necessitates the discovery of novel therapeutic options. This study investigated the anthelmintic properties and therapeutic potential of stonefish ichthyocrinotoxins (i.e., [...] Read more.
Parasitic gastrointestinal worms (i.e., helminths) remain a significant global health and economic burden. The increasing inefficacy of current anthelmintic drugs against parasitic diseases necessitates the discovery of novel therapeutic options. This study investigated the anthelmintic properties and therapeutic potential of stonefish ichthyocrinotoxins (i.e., secreted skin toxins). xWORM (xCELLigence Worm Real-Time Motility Assay) was used to evaluate the anthelmintic activity of ichthyocrinotoxins from two stonefish species, Synanceia horrida (Estuarine Stonefish) and Synanceia verrucosa (Reef Stonefish), against the infective third-stage larvae of Nippostrongylus brasiliensis (Rodent Hookworm). Both toxins demonstrated potent anthelmintic effects, with S. horrida ichthyocrinotoxin exhibiting greater potency (IC50 = 196.0 µg/mL) compared to ichthyocrinotoxin from S. verrucosa (IC50 = 329.7 µg/mL). Fractionation revealed that the anthelmintic activity of S. verrucosa is likely driven by synergistic interactions between the large (>3 kDa) and small (<3 kDa) components. In contrast, the small components isolated from S. horrida ichthyocrinotoxin were responsible for the majority of the observed activity, making them a more attractive therapeutic candidate. Furthermore, despite the cytotoxicity of crude S. horrida ichthyocrinotoxin against human skin and bile duct cell lines, the isolated small components exhibited potent anthelmintic effects (IC50 = 70.5 µg/mL) with negligible cytotoxicity (<10% decrease in survival at 100 µg/mL). While further research is necessary to fully characterise these compounds and assess their clinical suitability, this study highlights the potential of stonefish ichthyocrinotoxins as a novel source of anthelmintic therapeutics. Full article
(This article belongs to the Special Issue Venoms and Drugs)
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14 pages, 2964 KiB  
Article
The Secretome of Brain Endothelial Cells Exposed to the Pyrrolizidine Alkaloid Monocrotaline Induces Astrocyte Reactivity and Is Neurotoxic
by Letícia Oliveira Santos, Julita Maria Pereira Borges, Juliana Lago Leite, Mauricio Moraes Victor, Adriana Lopes da Silva, Cleonice Creusa dos Santos, Victor Diógenes Amaral da Silva, Ravena Pereira do Nascimento and Silvia Lima Costa
Toxins 2025, 17(2), 65; https://doi.org/10.3390/toxins17020065 - 1 Feb 2025
Abstract
Monocrotaline (MCT) has well-characterized hepatotoxic and pneumotoxic effects attributed to its active pyrrole metabolites. Studies have previously shown that astrocytes and neurons are targets of MCT, and that toxicity is attributed to astrocyte P450 metabolism to reactive metabolites. However, little is known about [...] Read more.
Monocrotaline (MCT) has well-characterized hepatotoxic and pneumotoxic effects attributed to its active pyrrole metabolites. Studies have previously shown that astrocytes and neurons are targets of MCT, and that toxicity is attributed to astrocyte P450 metabolism to reactive metabolites. However, little is known about MCT toxicity and metabolism by brain endothelial cells (BECs), cells that, together with astrocytes, are specialized in xenobiotic metabolism and neuroprotection. Therefore, in the present study, we evaluated the toxicity of MCT in BECs, and the effects on astrocyte reactivity and neuronal viability in vitro. MCT was purified from Crotalaria retusa seeds. BECs, obtained from the brain of adult Wistar rats, were treated with MCT (1–500 µM), and cell viability and morphology were analyzed after 24–72 h of treatment. Astrocyte/neuron co-cultures were prepared from the cortex of neonatal and embryonic Wistar rats, and the cultures were exposed to conditioned medium (secretome) derived from BECs previously treated with MCT (100–500 µM, SBECM100/500). MCT was not toxic to BECs at the concentrations used and induced a concentration-dependent increase in cell dehydrogenase after 72 h of treatment, suggesting resistance to damage and drug metabolism. However, exposure of astrocyte/neuron co-cultures to the SBECM for 24 h induced changes in the cell morphology, vacuolization, and overexpression of GFAP in astrocytes, characterizing astrogliosis, and neurotoxicity with a reduction in the length of neurites labeled for β-III-tubulin, effects that were MCT concentration-dependent. These results support the hypothesis that MCT neurotoxicity may be due to products of its metabolism by components of the BBB such as BECs and astrocytes, which may be responsible for the brain lesions and symptoms observed after intoxication. Full article
(This article belongs to the Special Issue Plant Toxin Emergency)
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24 pages, 7561 KiB  
Review
Neurotoxins Acting on TRPV1—Building a Molecular Template for the Study of Pain and Thermal Dysfunctions
by Florian Beignon, Margaux Notais, Sylvie Diochot, Anne Baron, Ziad Fajloun, Hélène Tricoire-Leignel, Guy Lenaers and César Mattei
Toxins 2025, 17(2), 64; https://doi.org/10.3390/toxins17020064 - 31 Jan 2025
Abstract
Transient Receptor Potential (TRP) channels are ubiquitous proteins involved in a wide range of physiological functions. Some of them are expressed in nociceptors and play a major role in the transduction of painful stimuli of mechanical, thermal, or chemical origin. They have been [...] Read more.
Transient Receptor Potential (TRP) channels are ubiquitous proteins involved in a wide range of physiological functions. Some of them are expressed in nociceptors and play a major role in the transduction of painful stimuli of mechanical, thermal, or chemical origin. They have been described in both human and rodent systems. Among them, TRPV1 is a polymodal channel permeable to cations, with a highly conserved sequence throughout species and a homotetrameric structure. It is sensitive to temperature above 43 °C and to pH below 6 and involved in various functions such as thermoregulation, metabolism, and inflammatory pain. Several TRPV1 mutations have been associated with human channelopathies related to pain sensitivity or thermoregulation. TRPV1 is expressed in a large part of the peripheral and central nervous system, most notably in sensory C and Aδ fibers innervating the skin and internal organs. In this review, we discuss how the transduction of nociceptive messages is activated or impaired by natural compounds and peptides targeting TRPV1. From a pharmacological point of view, capsaicin—the spicy ingredient of chilli pepper—was the first agonist described to activate TRPV1, followed by numerous other natural molecules such as neurotoxins present in plants, microorganisms, and venomous animals. Paralleling their adaptive protective benefit and allowing venomous species to cause acute pain to repel or neutralize opponents, these toxins are very useful for characterizing sensory functions. They also provide crucial tools for understanding TRPV1 functions from a structural and pharmacological point of view as this channel has emerged as a potential therapeutic target in pain management. Therefore, the pharmacological characterization of TRPV1 using natural toxins is of key importance in the field of pain physiology and thermal regulation. Full article
(This article belongs to the Special Issue Unlocking the Deep Secrets of Toxins)
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18 pages, 3313 KiB  
Article
Toxic Cyanopeptides Monitoring in Thermal Spring Water by Capillary Electrophoresis Tandem Mass Spectrometry
by Rocío Carmona-Molero, Laura Carbonell-Rozas, Ana M. García-Campaña, Monsalud del Olmo-Iruela and Francisco J. Lara
Toxins 2025, 17(2), 63; https://doi.org/10.3390/toxins17020063 - 31 Jan 2025
Abstract
Cyanobacteria are an ancient group of prokaryotes capable of oxygenic photosynthesis. Recently, thermal crises symptoms in hot springs have been associated with acute cyanopeptides poisoning. The aim of this work is to develop a fast, easy and reliable method to monitor the presence [...] Read more.
Cyanobacteria are an ancient group of prokaryotes capable of oxygenic photosynthesis. Recently, thermal crises symptoms in hot springs have been associated with acute cyanopeptides poisoning. The aim of this work is to develop a fast, easy and reliable method to monitor the presence of toxic cyanopeptides in geothermal waters. The analytical method based on capillary zone electrophoresis coupled with tandem mass spectrometry (CZE-MS/MS) was developed for the simultaneous determination of 14 cyanopeptides in less than 7.5 min. A basic 50 mM ammonium acetate buffer at pH 10.2 was selected as the background electrolyte, positive electrospray ionization (ESI+) was employed for all compounds, and a salting-out assisted liquid–liquid extraction (SALLE) protocol with acetonitrile as an extraction solvent and MgSO4 as an auxiliary salting-out agent was optimized as sample treatment. Six natural hot springs in the province of Granada (Andalucía, Spain) were sampled at the beginning of the summer season (June) and at the end (September). Biomass collected at two sample points (Santa Fe and Zújar) contained cyanobacteria cells from the genera Phormidium, Leptolyngbya, and Spirulina. Nevertheless, cyanotoxins covered by this work were not found in any of the water samples analyzed. The greenness and transferability of the method was evaluated highlighting its sustainability and applicability. Full article
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