Toxins

12 pages, 2153 KB

Open AccessReview

Aflatoxin Exposure and Human Health with a Focus on Northern Latin America

by Karen A. Corleto, Christian S. Alvarez, Manuel Ramirez-Zea, John D. Groopman and Katherine A. McGlynn

Toxins 2026, 18(1), 58; https://doi.org/10.3390/toxins18010058 - 22 Jan 2026

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Abstract

Aflatoxins, mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus, were discovered sixty-five years ago and remain a significant public health threat, particularly amid increasing instances of extreme weather events. Of the four principal forms of aflatoxins found in foods (B₁, [...] Read more.

Aflatoxins, mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus, were discovered sixty-five years ago and remain a significant public health threat, particularly amid increasing instances of extreme weather events. Of the four principal forms of aflatoxins found in foods (B₁, B₂, G₁, and G₂), aflatoxin B₁ is the most potent carcinogen. Aflatoxins commonly contaminate a variety of foodstuffs, with maize being among the most susceptible. Chronic exposure to aflatoxins has been linked to liver cancer, childhood stunting, gallbladder cancer, and other adverse health effects. Due to public health concerns related to the consumption of aflatoxin-contaminated foods, most countries have established regulatory limits. Here, we present estimated aflatoxin exposure per day derived from human biomarker data across many studies around the world spanning more than forty years. We specifically focus on the impact of dietary aflatoxin in northern Latin America, where assessment of the total problem remains limited. These findings suggest a multipronged toolkit could mitigate aflatoxin exposure in the region, which would help to decrease the health burden. Full article

(This article belongs to the Special Issue 65 Years On from Aflatoxin Discovery—a Themed Issue in Honor of Professor John D. Groopman)

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22 pages, 1604 KB

Open AccessReview

Strategies for Removal of Protein-Bound Uremic Toxins in Hemodialysis

by Joost C. de Vries, João G. Brás, Geert M. de Vries, Jeroen C. Vollenbroek, Fokko P. Wieringa, Joachim Jankowski, Marianne C. Verhaar, Dimitrios Stamatialis, Rosalinde Masereeuw and Karin G. F. Gerritsen

Toxins 2026, 18(1), 57; https://doi.org/10.3390/toxins18010057 - 22 Jan 2026

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Abstract

The removal of protein-bound uremic toxins (PBUTs) from the blood of kidney failure patients with conventional dialysis is limited. However, as their harmful effects and association with morbidity and mortality in dialysis patients are increasingly recognized, PBUTs have become important therapeutic targets. In [...] Read more.

The removal of protein-bound uremic toxins (PBUTs) from the blood of kidney failure patients with conventional dialysis is limited. However, as their harmful effects and association with morbidity and mortality in dialysis patients are increasingly recognized, PBUTs have become important therapeutic targets. In this review, PBUT removal with current state-of-the-art dialysis technologies and future perspectives are discussed. Strategies to enhance PBUT clearance include methods that interfere with PBUT–albumin binding, such as chemical displacers, high ionic strength, pH changes, or electromagnetic fields, thereby increasing the free fraction available for dialysis. While these methods have shown promise in vitro, and some also in vivo, long-term safety data are lacking. PBUT removal can also be increased by adsorption, either directly via hemoperfusion, or indirectly, e.g., via sorbents incorporated in a mixed-matrix membrane or dissolved in the dialysate. In the kidney, PBUTs are secreted in the proximal tubules; hence, a cell-based bioartificial kidney (BAK) that secretes PBUTs is proposed as an add-on to current dialysis. Yet both PBUT adsorption strategies and, in particular, BAKs face considerable challenges in upscaling and mass production at acceptable costs. In conclusion, many novel technologies are under development, all requiring further (pre)clinical testing and upscaling before these strategies can be applied in the clinic. Full article

(This article belongs to the Special Issue New Insights in Uremic Toxins and Toxin-Related Outcomes in Chronic Kidney Disease)

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17 pages, 4912 KB

Open AccessArticle

Aligning Minds in Spasticity Care—A Two-Phase Delphi-Dialogue Study of Patients and Professionals in Spain

by Helena Bascuñana-Ambrós, Jacobo Formigo-Couceiro, José Maria Climent-Barberá, Lluis Guirao-Cano, Michelle Catta-Preta, Alex Trejo-Omeñaca and Josep Maria Monguet-Fierro

Toxins 2026, 18(1), 56; https://doi.org/10.3390/toxins18010056 - 22 Jan 2026

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Abstract

Background: Spasticity, which occurs with certain neurological conditions, substantially affects quality of life, function, and social participation. Despite widespread botulinum toxin use, variability persists in patient information, access to specialized rehabilitation, and follow-up models. Methods: This two-phase Delphi-Dialogue Patients–Professionals study (DDPP), promoted by [...] Read more.

Background: Spasticity, which occurs with certain neurological conditions, substantially affects quality of life, function, and social participation. Despite widespread botulinum toxin use, variability persists in patient information, access to specialized rehabilitation, and follow-up models. Methods: This two-phase Delphi-Dialogue Patients–Professionals study (DDPP), promoted by SERMEF, integrated perspectives from 77 patients and 141 rehabilitation professionals. Phase 1 used parallel surveys to assess satisfaction, perceived effectiveness of botulinum toxin, communication preferences, and rehabilitation follow-up. Phase 2 applied Real-Time Delphi with 38 experts to generate consensus recommendations to improve spasticity management. Results: Patients and professionals agreed on botulinum toxin benefits, the importance of ongoing rehabilitation, and the value of hybrid (in-person/remote) follow-up. Key gaps concerned access to Physical Medicine and Rehabilitation services, clarity and timing of information, and shared goal setting. Experts translated these misalignments into 10 prioritized recommendations, with highest feasibility for actions standardizing access pathways, optimizing botulinum toxin use, reinforcing structured education, and consolidating hybrid rehabilitation models. Conclusions: The DDPP approach offers a reproducible framework to align stakeholder perspectives by converting quantified divergence into consensus-based innovation priorities. Implementing the recommendations—particularly those strengthening communication, education, and hybrid pathways regarding botulinum toxin treatment—may support more accessible, personalized, patient-centered spasticity care. Full article

(This article belongs to the Special Issue Botulinum Toxin in Neuro-Rehabilitation: Expanding Horizons in Spasticity and Beyond)

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19 pages, 1040 KB

Open AccessFeature PaperArticle

Megalomyrmex milenae Transcriptome Reveals a Complex Venom Cocktail

by Kyle S. Sozanski, Guilherme R. Coelho, Marcela Akemi Ishihara, Alonso Delgado and Rachelle M. M. Adams

Toxins 2026, 18(1), 55; https://doi.org/10.3390/toxins18010055 - 21 Jan 2026

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Abstract

Megalomyrmex ant species have a rich natural history that provides an interesting backdrop to understanding how venom has been shaped by evolution. However, like many other species in the tribe Solenopsidini, alkaloid investigations have dominated, limiting our understanding of the diversity of venom [...] Read more.

Megalomyrmex ant species have a rich natural history that provides an interesting backdrop to understanding how venom has been shaped by evolution. However, like many other species in the tribe Solenopsidini, alkaloid investigations have dominated, limiting our understanding of the diversity of venom components. Here we use transcriptomics to qualify and quantify the proteins and peptides within Megalomyrmex milenae, a species of ant native to the Panamanian rainforest along the Panama Canal. RNA transcripts associated with and over-expressed in the venom gland allow the description of putative toxins and other significant protein components of the venom cocktail. Among other constituents, we find signatures for pore-forming toxins, neurotoxins, carbohydrate-digesting enzymes, proteins which potentially enhance trail pheromone efficacy, and peptides implicated in antimicrobial activity. This work greatly enhances our understanding of Megalomyrmex venoms, showing a multifaceted functional venom profile similar to other ant species. However, proteomic and functional assays are needed to clarify the venom functions hypothesized in this work. Full article

(This article belongs to the Special Issue Transcriptomic and Proteomic Study on Animal Venom: Looking Forward)

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18 pages, 2176 KB

Open AccessArticle

The Venom Proteome and Immunorecognition Profile of Clinically Important Echis carinatus sochureki from Northwestern India Underscores the Need for Regionally Specific Antivenoms

by Akhilesh Kumar, Alka Sahu, Maya Gopalakrishnan, Avni Blotra, Vishal Kumar Rout, Sourish Kuttalam, Shibi Muralidar, Anita Malhotra and Karthikeyan Vasudevan

Toxins 2026, 18(1), 54; https://doi.org/10.3390/toxins18010054 - 21 Jan 2026

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Abstract

The saw-scaled viper Echis carinatus, one of the “Big Four” causes of snakebites in India, is found from Sri Lanka to eastern Iraq. To investigate clinical reports regarding the limited efficacy of Indian polyvalent antivenom (IPAV) against envenomation in Echis carinatus sochureki [...] Read more.

The saw-scaled viper Echis carinatus, one of the “Big Four” causes of snakebites in India, is found from Sri Lanka to eastern Iraq. To investigate clinical reports regarding the limited efficacy of Indian polyvalent antivenom (IPAV) against envenomation in Echis carinatus sochureki (ECS) in northwestern India, we obtained 22 snakes from three locations in Rajasthan and identified 148–174 toxin isoforms belonging to 21–25 toxin families in their venom using a bottom-up proteomics approach. All samples showed a high abundance of snake venom metalloproteinases (SVMPs), particularly SVMP class III. Other major components were phospholipases A₂, L-amino-acid oxidases, snake venom serine proteases and snaclecs (C-type lectins). Variation in venom composition among locations in Rajasthan, compared to E. c. carinatus (ECC) from southern India, was primarily due to differences in the relative abundance of these toxin families. Recognition of all venom components by IPAV was poor at lower antivenom concentrations. Notably, SVMP classes II and III were poorly recognized at all venom-to-antivenom ratios in all ECS venoms, and a plasma clotting assay revealed poor neutralization of procoagulant activity. This collaborative study highlights the need for the development of regional antivenoms to effectively treat snakebites in northwestern India. Full article

(This article belongs to the Special Issue Collaborative Approaches to Mitigation of Snakebite Envenoming)

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18 pages, 1439 KB

Open AccessArticle

High-Resolution LC–MS Characterization of Ramaria flavobrunnescens, a Coral Mushroom Toxic to Livestock, Reveals Fungal, Bacterial, and Eucalyptus Tree Metabolites

by Megan J. Kelman, Justin B. Renaud, Joey B. Tanney, Mizael Machado and Mark W. Sumarah

Toxins 2026, 18(1), 53; https://doi.org/10.3390/toxins18010053 - 20 Jan 2026

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Abstract

Ramaria flavobrunnescens is an ectomycorrhizal coral mushroom that is often found growing in eucalyptus forests. The mushroom has been linked to accidental ingestion-associated livestock poisonings in South America, though the toxicological agent has not yet been described. Mushroom samples identified as R. flavobrunnescens [...] Read more.

Ramaria flavobrunnescens is an ectomycorrhizal coral mushroom that is often found growing in eucalyptus forests. The mushroom has been linked to accidental ingestion-associated livestock poisonings in South America, though the toxicological agent has not yet been described. Mushroom samples identified as R. flavobrunnescens were analyzed by liquid chromatography high-resolution mass spectrometry (LC–MS/MS) to determine the potential source of the toxicity, and to provide a metabolomic profile of the species. Previously reported Ramaria secondary metabolites were detected, including ramarins, ramariolides, pistillarin and arsenic-containing compounds. A number of bacterial species were isolated from R. flavobrunnescens that produced iron-chelating cyclic peptides, which were detected in the mushroom samples. Interestingly, we detected a series of eucalyptus tree secondary metabolites in abundance from R. flavobrunnescens fruiting bodies, some of which have reported toxicities and bioactivities. To our knowledge, this is the first report of eucalyptus secondary metabolites in a mushroom. The diversity of secondary metabolites identified in the mushroom extracts provides insight into the potential complex ecological interactions between R. flavobrunnescens, its associated microbiota, and its mycorrhizal interaction with eucalyptus trees. Full article

(This article belongs to the Section Mycotoxins)

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3 pages, 187 KB

Open AccessReply

Reply to Peigneur et al. The Helix Ring Peptide U11 from the Venom of the Ant, Tetramorium bicarinatum, Acts as a Putative Pore-Forming Toxin, Not a New Kv1.3 Channel Blocker. Comment on “Boy et al. A New Kv1.3 Channel Blocker from the Venom of the Ant Tetramorium bicarinatum. Toxins 2025, 17, 379”

by Guillaume Boy, Laurence Jouvensal, Nathan Téné, Jean-Luc Carayon, Elsa Bonnafé, Françoise Paquet, Michel Treilhou, Karine Loth and Arnaud Billet

Toxins 2026, 18(1), 52; https://doi.org/10.3390/toxins18010052 - 19 Jan 2026

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Abstract

We thank Peigneur et al [...] Full article

(This article belongs to the Special Issue Unlocking the Deep Secrets of Toxins)

18 pages, 1940 KB

Open AccessArticle

Longitudinal, Multi-Cycle Evaluation of Passive Function Improvement in People with Arm Spasticity Treated with Botulinum Toxin A

by Stephen A. Ashford, Khan Buchwald, Klemens Fheodoroff, Jorge Jacinto, Ajit Narayanan, Richard J. Siegert, Christian Hannes and Lynne Turner-Stokes

Toxins 2026, 18(1), 51; https://doi.org/10.3390/toxins18010051 - 19 Jan 2026

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Abstract

Improvement in passive function (i.e., ease of caring for a limb) is a common goal for treatment of spasticity in the arm with botulinum toxin. A large international, observational, 2-year longitudinal study (ULIS-III, N = 953) was conducted in real-life practice. This original [...] Read more.

Improvement in passive function (i.e., ease of caring for a limb) is a common goal for treatment of spasticity in the arm with botulinum toxin. A large international, observational, 2-year longitudinal study (ULIS-III, N = 953) was conducted in real-life practice. This original secondary analysis examines whether improvement in passive function goals were met over repeated injection cycles. We report changes by cycle measured by the Passive Function sub-scale of the Arm Activity measure (ArmA-PF) and examine predictors of improvement and injection occurrence. Inclusion in this analysis was based on passive function being selected as a primary or secondary goal for one or more cycle of treatment (n = 542/953). Goals were assessed at the start and end of each cycle using the Goal Attainment Test score and the ArmA-PF. Over all cycles of treatment, goals were set for 1641/2187 injections (75.0%) and achieved in 1250 (76.2%). Significant improvements in ArmA-PF score were identified for at least six cycles (p < 0.001) with evidence of cumulative benefit over successive cycles. This occurred regardless of patient-related baseline characteristics, with the possible exception of some relationship with injection localization techniques. In conclusion, repeated botulinum toxin injections provide significant improvement in passive function, which was sustained over repeated cycles of treatment. Full article

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8 pages, 710 KB

Open AccessReview

Botulinum Toxin Treatment of Notalgia Paresthetica—A Critical Review and Update

by Ava Grace Tohidian, Shahroo Etemadmoghadam and Bahman Jabbari

Toxins 2026, 18(1), 50; https://doi.org/10.3390/toxins18010050 - 19 Jan 2026

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Abstract

Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December [...] Read more.

Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Full article

(This article belongs to the Special Issue Botulinum Toxins: Beyond the SNAP-25 Cleavage and New Insights on Pain Relief Mechanisms)

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16 pages, 2458 KB

Open AccessArticle

Reducing Aflatoxin Accumulation in Maize: Development and Performance of a Novel Biological Input

by Paloma Rhein, Marianela Bossa, María del Pilar Monge, Diego Giovanini, César Alfredo Barbero, Sofía Noemí Chulze, María Laura Chiotta and María Silvina Alaniz-Zanon

Toxins 2026, 18(1), 49; https://doi.org/10.3390/toxins18010049 - 17 Jan 2026

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Abstract

Aflatoxin contamination of maize by Aspergillus section Flavi constitutes a major health and economic concern. While biological control using non-toxigenic strains has proven effective, the increasing global food demand underscores the need for alternative carrier materials to replace seeds and grains. The aims [...] Read more.

Aflatoxin contamination of maize by Aspergillus section Flavi constitutes a major health and economic concern. While biological control using non-toxigenic strains has proven effective, the increasing global food demand underscores the need for alternative carrier materials to replace seeds and grains. The aims of the present study were (1) to develop an innovative macroporous starch polymer in which the biocontrol agent can grow and be transported to fields where the bioformulate is applied, and (2) to evaluate the effectiveness of this new formulate in reducing AF contamination in maize kernels in field trials, in comparison with the traditional formulate based on long-grain rice as a substrate. Several methods and different starch sources were tested, and the formulation consisting of 10% maize starch, 0.5% citric acid, 3% sucrose, 0.3% urea, and distilled water was the most effective. Furthermore, this bioformulate demonstrated a performance comparable to that of the traditional long-grain rice-based formulation, reducing AF accumulation by up to 81% in maize kernels under field conditions. The implementation of this macroporous starch polymer-based formulation, in combination with the biological control agent A. flavus AFCHG2, would not only reduce aflatoxin contamination in maize kernels but also minimise the use of food-grade seeds and grains for industrial purposes, thereby preserving their availability for human and animal nutrition. Consequently, this development could enhance the availability of these substrates for food and feed use, thereby contributing to improved safety and food security. Full article

(This article belongs to the Special Issue Mycotoxins in Food Safety: Challenges and Biocontrol Strategies)

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15 pages, 2366 KB

Open AccessArticle

Identification of a Novel Dihydroneopterin Aldolase as a Key Enzyme for Patulin Biodegradation in Lactiplantibacillus plantarum 6076

by Yixiang Shi, Wenli Yang, Aidi Ding, Yuan Wang, Yu Wang and Qianqian Li

Toxins 2026, 18(1), 48; https://doi.org/10.3390/toxins18010048 - 16 Jan 2026

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Abstract

Patulin (PAT) is a fatal mycotoxin that exerts serious threats to human and animal health. Biodegradation of PAT is considered to be one of the promising ways for controlling its contamination. In this study, Lactiplantibacillus plantarum 6076 (LP 6076) with reliable removal efficiency [...] Read more.

Patulin (PAT) is a fatal mycotoxin that exerts serious threats to human and animal health. Biodegradation of PAT is considered to be one of the promising ways for controlling its contamination. In this study, Lactiplantibacillus plantarum 6076 (LP 6076) with reliable removal efficiency on PAT was screened out from three lactic acid bacteria (LAB) strains. It was found that the PAT was eliminated through degradation by LP 6076, and the intracellular proteins played a crucial role in PAT degradation with the induction of PAT. The proteomic analysis showed that the response of LP 6076 to PAT was by a concerted effort to repair DNA damage, in parallel to adaptive changes in cell wall biosynthesis and central metabolism. Eleven differentially expressed proteins with high fold changes were picked out and identified as PAT degradation candidate enzymes. The 3D structures of the candidate enzymes were predicted, and molecular docking between the enzymes and PAT was performed. Five enzymes, including Acetoin utilization AcuB protein (AU), GHKL domain-containing protein (GHLK), Dihydroneopterin aldolase (DA), YdeI/OmpD-associated family protein (YDEL), and Transcription regulator protein (TR), could dock with PAT with lower affinity and shorter distance. Through molecular docking analysis, DA was ultimately identified as a potential key degrading enzyme. The choice of DA was substantiated by its superior combination of strong binding affinity and a productive binding pose with PAT. VAL84 and GLN51 residues of DA were likely the active sites, forming four hydrogen bonds with PAT. Our study could accelerate the commercial application of biodegradation toward PAT decontamination. Full article

(This article belongs to the Section Mycotoxins)

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15 pages, 4114 KB

Open AccessArticle

Biochemical and Genetic Characterization of Ergot Alkaloid Biosynthesis in Aspergillus aspearensis

by Jessica L. Fuss and Daniel G. Panaccione

Toxins 2026, 18(1), 47; https://doi.org/10.3390/toxins18010047 - 16 Jan 2026

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Abstract

Ergot alkaloids derived from lysergic acid have impacted humankind significantly as toxins in agriculture and as the foundations of several pharmaceuticals. Few fungi capable of producing lysergic acid derivatives have been found outside the family Clavicipitaceae. Based on its phylogenetic placement, we hypothesized [...] Read more.

Ergot alkaloids derived from lysergic acid have impacted humankind significantly as toxins in agriculture and as the foundations of several pharmaceuticals. Few fungi capable of producing lysergic acid derivatives have been found outside the family Clavicipitaceae. Based on its phylogenetic placement, we hypothesized the recently described fungus Aspergillus aspearensis (Aspergillaceae) would synthesize lysergic acid amides. Cultures of A. aspearensis produced abundant lysergic acid α-hydroxyethylamide (LAH) and lesser amounts of other lysergic acid derivatives. Conidia contained high concentrations of ergot alkaloids, whereas sclerotia contained significantly less. Approximately half of the ergot alkaloids produced were secreted into the culture medium. When spores of A. aspearensis were injected into larvae of the model insect Galleria mellonella, larvae died at a significantly faster rate than control larvae. The fungus produced ergot alkaloids during insect pathogenesis and later produced conidia and sclerotia on cadavers, indicating it can complete its life cycle in an insect. The genome of A. aspearensis contained two complete ergot alkaloid synthesis gene clusters, similar to those of A. leporis; however, unlike its sister species, none of the ergot cluster genes were pseudogenized. Aspergillus aspearensis is a newly discovered source of ergot alkaloids and may be useful for studying and producing these important chemicals. Full article

(This article belongs to the Section Mycotoxins)

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16 pages, 3163 KB

Open AccessArticle

Functional Dissection of Leishmania major Membrane Components in Resistance to Cholesterol-Dependent Cytolysins

by Chaitanya S. Haram, Sebastian J. Salinas, Coleman Wilson, Salma Waheed Sheikh, Kai Zhang and Peter A. Keyel

Toxins 2026, 18(1), 46; https://doi.org/10.3390/toxins18010046 - 16 Jan 2026

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Abstract

Bacteria use cholesterol-dependent cytolysins (CDCs) to damage eukaryotes. While well-studied in mammals, the mechanisms by which CDCs bind to and kill protozoans remain unclear. CDCs bind to the human pathogen Leishmania major but only kill in the absence of sphingolipids. The contribution of [...] Read more.

Bacteria use cholesterol-dependent cytolysins (CDCs) to damage eukaryotes. While well-studied in mammals, the mechanisms by which CDCs bind to and kill protozoans remain unclear. CDCs bind to the human pathogen Leishmania major but only kill in the absence of sphingolipids. The contribution of other leishmanial membrane components to CDC binding and cytotoxicity remains unknown. Here, we used genetic knockouts and inhibitors to determine the contribution of key membrane components to CDC binding and killing in L. major. We analyzed toxin binding and killing using flow cytometry and Western blotting. Loss of the virulence factor GP63 enhanced toxicity of perfringolysin O but not streptolysin O. Plasmenylethanolamine and lipophosphoglycan had minimal contributions to CDC binding and cytotoxicity. Removal of sterols protected cells from CDCs yet failed to reduce binding. We used CDCs defective in engaging glycans or cholesterol to confirm that CDCs deficient in sterol binding, but not glycan binding, could bind to L. major. Thus, in non-mammalian systems, CDCs may rely on glycans for binding, while using sterols for pore formation. This suggests that CDCs may not be sterol-specific probes in some non-mammalian systems. We conclude that early-branching eukaryotes use distinct mechanisms from mammals to limit CDC pore formation and killing. Full article

(This article belongs to the Special Issue Pore-Forming Toxins: From Structure to Function)

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23 pages, 3449 KB

Open AccessArticle

A Cell-Based Potency Assay for Determining the Relative Potency of Botulinum Neurotoxin A Preparations Using Manual and Semi-Automated Procedures

by F. Mark Dunning, Sara Hendrickson, Serena Wolfe, Dan Harding, Theresa Geurs, Timothy M. Piazza, Thomas A. Little and Ward C. Tucker

Toxins 2026, 18(1), 45; https://doi.org/10.3390/toxins18010045 - 15 Jan 2026

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Abstract

Cell-based potency assays (CBPAs) are required for the potency testing and commercial release of botulinum neurotoxin (BoNT)-based drug products. These CBPAs must account for the toxin’s biological activities while meeting regulatory guidelines for precision and accuracy. Here, studies describe the characterization and qualification [...] Read more.

Cell-based potency assays (CBPAs) are required for the potency testing and commercial release of botulinum neurotoxin (BoNT)-based drug products. These CBPAs must account for the toxin’s biological activities while meeting regulatory guidelines for precision and accuracy. Here, studies describe the characterization and qualification of the BoSapient CBPA and demonstrate that it is fit for use as a relative potency assay for BoNT/A-containing samples. The CBPA is operated in a 96-well plate format and relies upon the fluorescence emissions of a reporter that directly responds to BoNT/A activity. The BoSapient cell line expresses the BoNT/A-receptors SV2 and complex gangliosides, is responsive only to intact BoNT/A, and can robustly detect picomolar and sub-picomolar BoNT/A quantities, making the CBPA appropriate for quantifying BoNT/A-based drug products. The cell line was passaged 30 times without significant loss of reporter expression or BoNT/A sensitivity. Manual and semi-automated CBPA methods were developed and qualified according to regulatory guidelines and shown to have low bias (<4% from expected) and high precision (standard deviation < 8) across all test concentrations. Furthermore, the semi-automated method using the CBPA is demonstrated to improve intermediate precision by 39% compared to the manual method, while reducing operator dependency during method execution. Full article

(This article belongs to the Section Bacterial Toxins)

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3 pages, 437 KB

Open AccessComment

The Helix Ring Peptide U11 from the Venom of the Ant, Tetramorium bicarinatum, Acts as a Putative Pore-Forming Toxin, Not a New Kv1.3 Channel Blocker. Comment on Boy et al. A New Kv1.3 Channel Blocker from the Venom of the Ant Tetramorium bicarinatum. Toxins 2025, 17, 379

by Steve Peigneur, Diogo Tibery and Jan Tytgat

Toxins 2026, 18(1), 44; https://doi.org/10.3390/toxins18010044 - 15 Jan 2026

Cited by 1 | Viewed by 267

Abstract

Boy et al [...] Full article

(This article belongs to the Special Issue Unlocking the Deep Secrets of Toxins)

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13 pages, 1433 KB

Open AccessArticle

Presynaptic Terminal Proteins and Nicotinic Receptors Are Depleted from Mouse Parasympathetic Ganglionic Junctions Paralysed with Botulinum Neurotoxin Type A

by Ahmed Al-Sabi and Gary W. Lawrence

Toxins 2026, 18(1), 43; https://doi.org/10.3390/toxins18010043 - 14 Jan 2026

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Abstract

Plasticity is fundamental to the development, strengthening, and maintenance of healthy synaptic connections and recovery from injury in both the central and peripheral nervous systems. Yet, the processes involved are poorly understood. Herein, using a combination of patch-clamp electrophysiology and immuno-fluorescence confocal microscopy [...] Read more.

Plasticity is fundamental to the development, strengthening, and maintenance of healthy synaptic connections and recovery from injury in both the central and peripheral nervous systems. Yet, the processes involved are poorly understood. Herein, using a combination of patch-clamp electrophysiology and immuno-fluorescence confocal microscopy in adult mice, it is shown that blockade of synaptic transmission at submandibular ganglion junctions exposed to botulinum neurotoxin type A was accompanied by a rapid and striking decline in the abundance of synaptic vesicle markers—SV2, vesicle-associated membrane protein 2, and vesicular acetylcholine transporter—plus SNAP-25 (cleaved and intact) and postsynaptic α7 nicotinic acetylcholine receptors. Such alterations by the neurotoxin of parasympathetic synapses contrast starkly with the stability of postsynaptic proteins at nearby skeletal neuromuscular junctions. Both neurotransmission and the expression of SV2 and α7 nicotinic acetylcholine receptors remained depressed for 4 weeks, with full recovery of synaptic function delayed for more than 8 weeks. These novel findings may explain the relatively slow recovery of autonomic function after botulism or following therapeutic injections to alleviate hypersecretory disorders. Full article

(This article belongs to the Special Issue Botulinum Toxin Therapy for Diseases in the Oral and Maxillofacial Regions)

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27 pages, 3283 KB

Open AccessArticle

Fungal Contamination of Dairy Feed and Major Mycotoxin Transfer: A Risk Evaluation for Animal Exposure and Health

by Ioana Poroșnicu, Luminița-Iuliana Ailincăi, Mădălina Alexandra Davidescu and Mihai Mareș

Toxins 2026, 18(1), 42; https://doi.org/10.3390/toxins18010042 - 13 Jan 2026

Viewed by 475

Abstract

This study was focused on the assessment of fungal occurrence, mycotoxin dynamics, aflatoxin carry-over, and associated biochemical responses in dairy cattle. Moisture emerged as the dominant factor for fungal communities, promoting the co-proliferation of fungal genera adapted to high water activity conditions (a [...] Read more.

This study was focused on the assessment of fungal occurrence, mycotoxin dynamics, aflatoxin carry-over, and associated biochemical responses in dairy cattle. Moisture emerged as the dominant factor for fungal communities, promoting the co-proliferation of fungal genera adapted to high water activity conditions (a_w > 0.90) and antagonism against xerotolerant and xerophilic species. Aspergillus spp. dominated dry substrates (a_w < 0.75), Fusarium spp. showed strong positive associations with high-moisture matrices (a_w > 0.90), and Penicillium spp. exhibited intermediate, substrate-dependent behavior. Mycotoxin levels fluctuated non-linearly, independently of fungal counts: ochratoxin A (OTA) concentrations in corn silage increased from approximately 12 μg/kg at the onset of the ensiling period to >240 μg/kg at silo opening, indicating dynamic mycotoxin accumulation during storage, while zearalenone (ZEA) oscillated from 40 to 170 µg/kg. Despite the variation in total aflatoxins (AFLA-T) across feed matrices, aflatoxin M1 (AFM1) in milk remained low (0.0020–0.0093 μg/kg), confirming limited carry-over. Serum biochemical parameters—alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (BIL-T), total protein (PROT-T)—remained within physiological limits, yet multivariate analyses revealed metabolic modulation linked to aflatoxin exposure. AFM1 explained >7% of the variance in serum biochemical profiles according to PERMANOVA (p = 0.002), showed significant MANOVA effect (Pillai = 0.198), and displayed a significant canonical association (p < 10⁻¹³). Linear discriminant analysis further separated Normal vs. Borderline hepatic profiles, indicating subclinical physiological adaptation to chronic low-dose exposure. Full article

(This article belongs to the Special Issue Risk Assessment of Mycotoxins: Challenges and Emerging Threats)

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16 pages, 3909 KB

Open AccessArticle

Analysis of the Combined Toxic Effects of AFB1, DON, and OTA Complex Contamination in Caco-2, HK-2, SK-N-SH and HepG2 Cells

by Hanke Zhao, Xiaohu Zhai, Weihua He, Zheng Jing, Dengyan Wang and Junhua Yang

Toxins 2026, 18(1), 41; https://doi.org/10.3390/toxins18010041 - 12 Jan 2026

Viewed by 302

Abstract

Aflatoxin B1 (AFB1), deoxynivalenol (DON), and ochratoxin A (OTA) are common mycotoxins that frequently co-occur in cereals and pose potential risks to animal and human health. This study investigated the cytotoxic effects of AFB1, DON, and OTA, individually and in binary and ternary [...] Read more.

Aflatoxin B1 (AFB1), deoxynivalenol (DON), and ochratoxin A (OTA) are common mycotoxins that frequently co-occur in cereals and pose potential risks to animal and human health. This study investigated the cytotoxic effects of AFB1, DON, and OTA, individually and in binary and ternary combinations, in four human-derived cell lines representing major target organs (Caco-2, HepG2, HK-2, and SK-N-SH). Individual toxin exposure revealed cell type–dependent sensitivity, with DON generally exhibiting the strongest cytostatic effect. Combined exposure analysis showed distinct interaction patterns across cell models, including antagonistic effects of AFB1 + OTA in most cell lines, dose-dependent interactions of DON + OTA, and low-dose synergistic effects in specific combinations. Overall, the results demonstrate that mycotoxin interactions are highly dependent on dose and target cell type, and that low-dose co-contamination may enhance toxicological risks, underscoring the importance of considering combined mycotoxin exposure in health risk assessment. Full article

(This article belongs to the Special Issue Mycotoxin Co-Contamination：Cooccurrence, Interaction, Toxicological Mechanisms and, Risk Assessment in Agri-Products, Food and Feed)

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11 pages, 8813 KB

Open AccessArticle

Omphalotus yunnanensis: A New Poisonous Mushroom Discovered from China Based on Morphological, Molecular and Toxin-Detection Evidence

by Zhong-Feng Li, Jing Zhang, Xiang-Dong Min, Hong-Shun Zhang, Li Chen, Dai-Neng Li, Yi-Zhe Zhang, Ming-Xuan Yuan, Zhi-Yuan Liu, Jia-Ju Zhong, Meng-Huan Ruan and Hai-Jiao Li

Toxins 2026, 18(1), 40; https://doi.org/10.3390/toxins18010040 - 12 Jan 2026

Cited by 1 | Viewed by 395

Abstract

In the past few years, several mushroom poisoning incidents caused by Omphalotus species have occurred in China. In addition to O. guepiniformis and O. olearius, a new white Omphalotus species, O. yunnanensis, was discovered in Southwestern and Southern China based on [...] Read more.

In the past few years, several mushroom poisoning incidents caused by Omphalotus species have occurred in China. In addition to O. guepiniformis and O. olearius, a new white Omphalotus species, O. yunnanensis, was discovered in Southwestern and Southern China based on morphological, molecular and toxin-detection evidence. Omphalotus yunnanensis is characterized by its small, cream to white basidiomata with a hygrophanous pileal surface, non-bioluminescent lamellae, broadly ellipsoid to subglobose basidiospores (8–12.5 × 7–10 μm), fusoid to ventricose cheilocystidia with occasional apical outgrowths, cream to white pileipellis composed of thick-walled, subsoil to solid hyphae, clavate, and fusoid to ventricose caulocystidia with occasional apical outgrowths. The species has been discovered in tropical to subtropical areas in Southwestern and Southern China. Phylogenetic analyses based on ITS and nrLSU showed that the new species clustered with the Australasian species O. nidiformis, but can be easily distinguished by its smaller, white to cream pileus, non-bioluminescent lamellae, larger basidiospores and growing on Fagaceae species. Illudin S was detected in this new species using UPLC-MS/MS, at 6.98 to 86.1 mg/kg of the content (dry weight), while no illudin M was detected. Full article

(This article belongs to the Section Mycotoxins)

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23 pages, 33068 KB

Open AccessArticle

TMT Quantitative Proteomics Reveals the Molecular Mechanism Behind Meat Quality Changes in Nile Tilapia Exposed to Environmental Concentrations of Microcystin-LR

by Yichao Li, Huarong Xiao, Jun Xie, Liping Liu, Fajun Jiang, Jingqiu Liao and Ermeng Yu

Toxins 2026, 18(1), 39; https://doi.org/10.3390/toxins18010039 - 12 Jan 2026

Viewed by 337

Abstract

This study investigated the effects of chronic MC-LR exposure (0 μg/L [Control], 1 μg/L [M1], 3 μg/L [M3], 10 μg/L [M10], and 30 μg/L [M30]) on the muscle nutrient composition, meat quality, and muscle proteomic profile of Nile tilapia (Oreochromis niloticus). [...] Read more.

This study investigated the effects of chronic MC-LR exposure (0 μg/L [Control], 1 μg/L [M1], 3 μg/L [M3], 10 μg/L [M10], and 30 μg/L [M30]) on the muscle nutrient composition, meat quality, and muscle proteomic profile of Nile tilapia (Oreochromis niloticus). In the high-dose group (M30), MC-LR exposure compromised the muscle antioxidant status of Nile tilapia, resulting in reduced meat quality, as evidenced by decreased pH value and water-holding capacity, elevated lipid/protein oxidation, and altered texture parameters (shear force and fragmentation index). Proteomic analysis further revealed a downregulation of proteins associated with ribosomes, suggesting an impairment of muscle protein synthesis in the M30 group. Moreover, despite chronic exposure, only low levels of MC-LR accumulated in the muscle tissue, indicating a negligible health risk to consumers. Collectively, these findings offered valuable insights into the impact of environmental MC-LR contamination on fish muscle quality and nutritional value. Full article

(This article belongs to the Topic Recent Advances in Harmful Algal Blooms in Freshwater and Marine Systems)

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16 pages, 851 KB

Open AccessArticle

Effect of Post-Harvest Management on Aspergillus flavus Growth and Aflatoxin Contamination of Stored Hazelnuts

by Alessia Casu, Giorgio Chiusa, Eugenio Zagottis, Giuseppe Genova and Paola Battilani

Toxins 2026, 18(1), 38; https://doi.org/10.3390/toxins18010038 - 11 Jan 2026

Viewed by 451

Abstract

Hazelnut (Corylus avellana L.) is a major crop in the Caucasus region, but its safety is often threatened by Aspergillus flavus colonization and aflatoxin contamination. Although aflatoxins (AFs) are strictly regulated in the EU, the influence of post-harvest practices on fungal persistence [...] Read more.

Hazelnut (Corylus avellana L.) is a major crop in the Caucasus region, but its safety is often threatened by Aspergillus flavus colonization and aflatoxin contamination. Although aflatoxins (AFs) are strictly regulated in the EU, the influence of post-harvest practices on fungal persistence and AF accumulation remains poorly defined. A three-year study was conducted to evaluate the effects of drying protocols, storage temperature, and conservation practices on fungal growth and AF occurrence in hazelnuts from three producing regions of Azerbaijan. Freshly harvested nuts were subjected to two drying regimes: good drying (sun-exposed, mixed, protected from rewetting) and bad drying (shaded, piled, rewetted). After drying, samples were stored at cold (8–10 °C) or room temperature (18–22 °C). Fungal prevalence was determined by CFU counts with morphological and qPCR identification of Aspergillus section Flavi. AFs were quantified by HPLC, and water activity (a_w) was monitored during storage. Drying emerged as the decisive factor: bad drying consistently resulted in markedly higher fungal loads for A. section Flavi, with mean counts up to 1.3 log10 (CFU/g), compared with 0.8 log10 (CFU/g) under good drying, representing a 7-fold increase. In contrast, storage temperature and shell condition had negligible effects when nuts were properly dried. Aflatoxins were consistently below the 5 µg/kg EU limit for AFB₁ in traced and well-dried samples, whereas market samples occasionally exhibited AFB₁ concentrations >450 µg/kg. These findings highlight drying efficiency as the key determinant of fungal persistence and AF risk in hazelnut post-harvest management. Full article

(This article belongs to the Section Mycotoxins)

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12 pages, 882 KB

Open AccessArticle

Optimization of Ibuprofen Route and Dosage to Enhance Protein-Bound Uremic Toxin Clearance During Hemodialysis

by Víctor Joaquín Escudero-Saiz, Elena Cuadrado-Payán, María Rodríguez-García, Gregori Casals, Lida María Rodas, Néstor Fontseré, María del Carmen Salgado, Carla Bastida, Nayra Rico, José Jesús Broseta and Francisco Maduell

Toxins 2026, 18(1), 37; https://doi.org/10.3390/toxins18010037 - 11 Jan 2026

Viewed by 465

Abstract

Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT [...] Read more.

Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT clearance by competing for albumin-binding sites, but the optimal dose and route of administration remain unclear. The aim of this study was to evaluate the effect of different ibuprofen doses, infusion durations, and routes of administration on the removal of IS and pCS during on-line hemodiafiltration (OL-HDF). In this prospective, single-centre, crossover study, 21 chronic haemodialysis patients receiving intradialytic analgesia underwent nine OL-HDF sessions. Ibuprofen was administered at two doses (400 or 800 mg) either in the arterial pre-filter line (infusion over 1 h, 2 h, or 3 h) or in the venous post-filter line (30 min). Reduction ratios (RR) of total IS and pCS were determined by LC-MS and corrected for haemoconcentration. Statistical analysis included repeated-measures ANOVA with post-hoc testing. Baseline RR for IS and pCS were 53.7 ± 9.9% and 47.1 ± 10.9%, respectively. The highest RR was achieved with 800 mg ibuprofen infused via the arterial line over 2 h (IS: 60.8 ± 8.6%; pCS: 57.8 ± 9.7%). All arterial-line 800 mg regimens and the 3-h 400 mg infusion significantly improved pCS clearance versus baseline; IS clearance improved significantly only with arterial-line 800 mg regimens and with the 400 mg 3-h infusion. Infusion rate (1–3 h) had no significant effect on RR within the same dose group. Pain scores decreased significantly after dialysis regardless of ibuprofen regimen. Arterial-line administration of ibuprofen enhances total IS and pCS removal during OL-HDF, with higher doses yielding greater clearance. Prolonged low-dose infusion appears similarly effective for pCS and may reduce systemic exposure, potentially lowering toxicity risk. These findings support the arterial line as the preferred route for displacer administration in clinical practice. Full article

(This article belongs to the Special Issue Uremic Toxins and Chronic Kidney Disease)

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23 pages, 6607 KB

Open AccessArticle

Crotoxin B from the South American Rattlesnake Crotalus vegrandis Blocks Voltage-Gated Calcium Channels Independent of Its Intrinsic Catalytic Activity

by Markus Eicheldinger, Erick Miranda-Laferte, Francisco Castilla, Nadine Jordan, Beatrix Santiago-Schübel and Patricia Hidalgo

Toxins 2026, 18(1), 36; https://doi.org/10.3390/toxins18010036 - 10 Jan 2026

Viewed by 312

Abstract

Neurotoxicity following South American Crotalus rattlesnake bite is primarily caused by crotoxin, the most abundant component in their venom. Despite the central role of voltage-gated calcium channels (Ca_V) in neurotransmission, direct targetability by crotoxin has been poorly explored. Crotoxin is a [...] Read more.

Neurotoxicity following South American Crotalus rattlesnake bite is primarily caused by crotoxin, the most abundant component in their venom. Despite the central role of voltage-gated calcium channels (Ca_V) in neurotransmission, direct targetability by crotoxin has been poorly explored. Crotoxin is a non-covalent heterodimer formed by an acidic subunit (CA) and a basic toxic phospholipase A₂ subunit (CB). Here, we chromatographically isolated the CB subunit from Crotalus vegrandis and studied its effect on Ca_V heterologously expressed in tsA201 cells using the whole-cell patch-clamp technique. Mass spectrometry analysis identified a protein that matched with 97% sequence coverage the CBc isoform from Crotalus durissus terrificus. Isolated CB exhibited moderate phospholipase activity that was not correlated to its cytotoxic effect on cultured tsA201 cells. Using Ba²⁺ as a charge carrier to prevent the enzymatic activity, we found that CB inhibited currents mediated by the N-type Ca_V2.2 and Ca_V1.2 L-type calcium channels, in a dose–dependent manner, with higher potency for the latter, and negligible changes in the voltage dependence of channel activation. Our results reveal a novel phospholipase-independent biological activity and a molecular target of CB providing new insights into the pathophysiology of Crotalus snakebite envenoming with potential clinical therapeutic implications. Full article

(This article belongs to the Special Issue Peptide Toxins—Discovery, Mechanisms of Action, and Therapeutic Potential)

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29 pages, 7062 KB

Open AccessReview

Advances in Clostridial Neurotoxins: Passage of the Intestinal Barrier and Targeting of Specific Neuronal Cells

by Michel R. Popoff

Toxins 2026, 18(1), 35; https://doi.org/10.3390/toxins18010035 - 10 Jan 2026

Viewed by 509

Abstract

Clostridial neurotoxins, botulinum neurotoxins (BoNTs), and tetanus neurotoxin (TeNT) are potent toxins responsible for severe diseases, botulism and tetanus, respectively. BoNTs associate with non-toxic proteins (non-toxic non-hemagglutinin, hemagglutinins, and OrfXs), which protect BoNTs against acidic pH and protease degradation and facilitate BoNT passage [...] Read more.

Clostridial neurotoxins, botulinum neurotoxins (BoNTs), and tetanus neurotoxin (TeNT) are potent toxins responsible for severe diseases, botulism and tetanus, respectively. BoNTs associate with non-toxic proteins (non-toxic non-hemagglutinin, hemagglutinins, and OrfXs), which protect BoNTs against acidic pH and protease degradation and facilitate BoNT passage through the intestinal barrier. TeNT enters motor neurons and undergoes a retrograde axonal transport until the target inhibitory interneurons in the central nervous system. BoNTs and TeNT recognize specific cell surface receptors which consist of complex sets of protein(s)-glycan-gangliosides and determine specific cell entry pathways. Recent data on structural and functional investigations of BoNT and TeNT receptors bring a better understanding of toxin trafficking in the host and entry into target neuronal cells, which is useful for the development of updated strategies of prevention and treatment of the corresponding diseases. Since clostridial neurotoxins, notably BoNTs, are important therapeutic tools, detailed knowledge of their activity opens the way of the development of engineered molecules for specific clinical applications. Full article

(This article belongs to the Section Bacterial Toxins)

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16 pages, 3064 KB

Open AccessArticle

Curcumin Mitigates Fumonisin B₁-Induced Ovarian Toxicity in Peak-Laying Ducks via Hormone Metabolic Protection and Enhanced Reproductive Resilience

by Lihua Wang, Rui Liang, Qingyun Cao, Zhiwei Hou, Ali Mujtaba Shah, Qiuyi Deng, Xue Li, Jinze Li, Jiaqing Chen, Lukuyu A. Bernard, Muhammad Kashif Saleemi, Lin Yang and Wence Wang

Toxins 2026, 18(1), 34; https://doi.org/10.3390/toxins18010034 - 9 Jan 2026

Viewed by 377

Abstract

The objective of this study was to evaluate the protective effect of curcumin (Cur) on reproductive toxicity induced by fumonisin B₁ (FB₁) in laying ducks during the peak egg-laying period. A total of seventy-two 50-week-old Cherry Valley ducks were randomly [...] Read more.

The objective of this study was to evaluate the protective effect of curcumin (Cur) on reproductive toxicity induced by fumonisin B₁ (FB₁) in laying ducks during the peak egg-laying period. A total of seventy-two 50-week-old Cherry Valley ducks were randomly assigned to four groups: control, FB₁ (30 mg/kg), Cur (200 mg/kg), and Cur + FB₁ (200 mg/kg + 30 mg/kg). The experiment lasted for 35 days. Our results showed that cur supplementation effectively restored the reductions in final body weight (p = 0.005) and oviduct length (p = 0.020) induced by FB₁ exposure. Residual FB₁ concentrations in serum, liver, and ovaries were markedly increased in the FB₁-treated group, while Cur significantly decreased the FB₁ residual in duck liver (p < 0.05). Meanwhile, Cur supplementation markedly counteracted the FB₁-induced reductions in serum total protein, albumin, triglycerides, and high-density lipoprotein induced by FB₁ exposure. Cur supplementation effectively regulated FB₁-induced oxidative stress, inflammation, and endocrine disruption. Specifically, Cur lowered FB₁-induced malondialdehyde levels (p < 0.010), attenuated interleukin-1β increase (p = 0.083), and reversed the reduction in immunoglobulin G levels. FB increased the levels of hormones associated with duck reproduction, including estradiol, follicle-stimulating hormone, and luteinizing hormone; in contrast, curcumin supplementation decreased the levels of these hormones (p < 0.010). Histopathological analysis revealed that Cur significantly alleviated the inflammation and necrosis in the liver, kidneys, ovaries, and oviducts induced by FB₁. In conclusion, dietary Cur supplementation effectively alleviated FB₁-induced reproductive toxicity in laying ducks by enhancing antioxidant capacity, improving lipid metabolism, and restoring hormonal homeostasis. Full article

(This article belongs to the Special Issue Adverse Effects of Co-Contaminated Mycotoxins and Strategies for Their Mitigation)

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21 pages, 692 KB

Open AccessSystematic Review

Botulinum Toxin Type A for the Prevention of Migraines: An Umbrella Review of Systematic Reviews

by Goli Chamani, Hajer Jasim, Ava Minston, Marlon Ferreira Dias, Rodrigo Lorenzi Poluha, Daniela A. Godoi Gonçalves, Maria Christidis, Essam Ahmed Al-Moraissi, Nikolaos Christidis, Giancarlo De la Torre Canales and Malin Ernberg

Toxins 2026, 18(1), 33; https://doi.org/10.3390/toxins18010033 - 9 Jan 2026

Viewed by 709

Abstract

Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraines; however, uncertainty remains regarding its comparative efficacy and safety. Thus, we aimed to summarize current evidence from high-quality systematic reviews of the therapeutic effects of BoNT-A in migraine management. An [...] Read more.

Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraines; however, uncertainty remains regarding its comparative efficacy and safety. Thus, we aimed to summarize current evidence from high-quality systematic reviews of the therapeutic effects of BoNT-A in migraine management. An umbrella review was conducted following PRISMA guidelines and registered in PROSPERO. High-quality systematic reviews with meta-analysis evaluating BoNT-A efficacy were identified through five databases up to August 2024. Primary outcomes included monthly headache frequency and severity. Methodological quality and risk of bias were assessed using the umbrella review checklist. Fourteen articles were included. Overall, quantitative evidence indicated favorable effects of BoNT-A compared with placebo for chronic migraines, across headache frequency, headache severity, and acute medication use, but less efficacy than topiramate and the CGRP monoclonal antibodies (CGRPmAbs) galcanezumab and fremanezumab. Though the adverse events were frequent, BoNT-A was generally well-tolerated. Comparative data suggested superior tolerability versus topiramate and a safety profile like CGRPmAbs. Although botulinum toxin type A is widely used as a preventive treatment for chronic migraines, the available evidence supports its efficacy at a moderate level. Further head-to-head and long-term analyses are needed to clarify its comparative role alongside newer biologic treatments. Full article

(This article belongs to the Special Issue Botulinum Toxins: Beyond the SNAP-25 Cleavage and New Insights on Pain Relief Mechanisms)

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21 pages, 1968 KB

Open AccessReview

The Difficulties in Demonstrating That Aflatoxin Reduction Improves Stunting in Developing World Regions

by Paul C. Turner and Erica Phillips

Toxins 2026, 18(1), 32; https://doi.org/10.3390/toxins18010032 - 9 Jan 2026

Viewed by 431

Abstract

Aflatoxins are highly toxic secondary metabolites that contaminate dietary staples in many developing world regions, with hundreds of millions of people estimated to be chronically exposed. In this review, we summarize the evidence about AF exposure assessment and its relationship to stunting. Despite [...] Read more.

Aflatoxins are highly toxic secondary metabolites that contaminate dietary staples in many developing world regions, with hundreds of millions of people estimated to be chronically exposed. In this review, we summarize the evidence about AF exposure assessment and its relationship to stunting. Despite multiple attempts, this question has eluded a strong scientific conclusion due to the nature of the toxin and exposure, the disparate methods used for assessment, and the ethical difficulties of studying a toxin in low-resource settings. We highlight current challenges in defining these relationships, how this has reduced the ability to draw conclusions in this area, and approaches to overcome these to advance the field. Current reviews tend to report mixed associations, but typically lack critique of the study designs, and a limited understanding of patterns of aflatoxin exposure coupled with a probable variable threshold for effect. We highlight the potential diverse patterns of AF exposure over time and how that may influence study design to address this critical public health issue. Full article

(This article belongs to the Special Issue 65 Years On from Aflatoxin Discovery—a Themed Issue in Honor of Professor John D. Groopman)

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18 pages, 4241 KB

Open AccessArticle

Chimeric Antibody Engineering Against Bacillus anthracis Lethal Toxin: Neutralization Efficacy and Mechanism of Action

by Olga V. Kalmantaeva, Maksim A. Marin, Anastasia A. Ershova, Alena K. Ryabko, Yana O. Romanenko, Tatyana I. Kombarova, Ivan A. Dyatlov and Victoria V. Firstova

Toxins 2026, 18(1), 31; https://doi.org/10.3390/toxins18010031 - 9 Jan 2026

Viewed by 401

Abstract

Bacillus anthracis has three main virulence factors: an extracellular capsule and two binary toxins (lethal toxin—consists of a lethal factor and a protective antigen, and edema toxin—consists of an edema factor and a protective antigen). In the Russian Federation, the epidemiological situation regarding [...] Read more.

Bacillus anthracis has three main virulence factors: an extracellular capsule and two binary toxins (lethal toxin—consists of a lethal factor and a protective antigen, and edema toxin—consists of an edema factor and a protective antigen). In the Russian Federation, the epidemiological situation regarding anthrax infection remains unfavorable. In the late stages of an anthrax infection, antibiotic therapy becomes ineffective and the patient dies within 24 h as a large amount of lethal toxin accumulates in the patient’s blood. Antibodies capable of neutralising lethal toxin (LT) can be an effective treatment for these patients. The objective of the study was to construct a chimeric monoclonal antibody targeting the protective antigen of the LT and to elucidate its mechanism of toxin neutralization. In this work, a chimeric monoclonal antibody (xi1E10) directed against the protective antigen was successfully produced. Both in vitro and in vivo experiments demonstrated the capacity of xi1E10 to neutralize lethal toxin. Confocal microscopy revealed that xi1E10 effectively suppresses the formation of a functional pore, thereby blocking the translocation of the lethal factor into the cytosol. These findings indicate that the monoclonal antibody xi1E10 represents a promising candidate for the development of a therapeutic drug. Full article

(This article belongs to the Special Issue Anthrax Toxin Chronicles: Celebrating 70 Years of Scientific Breakthroughs in Chemistry, Biology, and Toxicology)

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5 pages, 214 KB

Open AccessEditorial

Animal Venoms for Drug Discovery: A Constantly Evolving Research Field

by Ziad Fajloun, Rabih Roufayel and Mohamad Rima

Toxins 2026, 18(1), 30; https://doi.org/10.3390/toxins18010030 - 8 Jan 2026

Viewed by 377

Abstract

Animal venoms, complex mixtures of molecules refined over thousands of years of evolution, represent far more than a simple defense or predatory system in venomous animals. [...] Full article

(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)

15 pages, 1409 KB

Open AccessReview

The Pathological Role of LDL in Membranous Nephropathy and Diabetic Nephropathy and the Protective Efficacy of LDL Apheresis: A Narrative Review

by Goh Kodama, Kensei Taguchi, Yusei Wada, Kaoru Nakano, Ryo Shibata and Kei Fukami

Toxins 2026, 18(1), 29; https://doi.org/10.3390/toxins18010029 - 8 Jan 2026

Viewed by 513

Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide. One-third of patients with DN develop primary glomerulonephritis, and membranous nephropathy (MN) is the most common concurrent glomerulonephritis. Nephrotic syndrome (NS) due to DN and MN is often refractory to immunosuppressants [...] Read more.

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide. One-third of patients with DN develop primary glomerulonephritis, and membranous nephropathy (MN) is the most common concurrent glomerulonephritis. Nephrotic syndrome (NS) due to DN and MN is often refractory to immunosuppressants because increased levels of low-density lipoprotein (LDL) not only accelerates kidney injury but also reduce the bioavailability of cyclosporine, a first-line immunosuppressant for MN. Given the pathological role of LDL, especially oxidized LDL, reducing LDL cholesterol levels can help achieve remission of NS and halt the progression of kidney injury. Although some lipoproteins are not excreted by the kidneys, excessive LDL, including oxidized LDL, can be considered uremic toxic-like factors that contribute to the development of NS or DN. We encountered a 74-year-old patient with concomitant DN and MN who achieved complete remission following additional LDL apheresis (LDL-A) with immunosuppressant therapy. Here, we provide a narrative review summarizing the role of LDL, especially ox-LDL, in the progression of DN and glomerulonephritis, including MN, and discuss the therapeutic rationale for LDL-A. We also present a representative case of concomitant MN and DN refractory to conventional immunosuppression who achieved clinical improvement following LDL-A. Full article

(This article belongs to the Special Issue The Role of Uremic Toxins in Comorbidities of Chronic Kidney Disease)

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